Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles.

PubMed

Bachar, Michal; Mandelbaum, Amitai; Portnaya, Irina; Perlstein, Hadas; Even-Chen, Simcha; Barenholz, Yechezkel; Danino, Dganit

2012-06-10

β-casein is an amphiphilic protein that self-organizes into well-defined core-shell micelles. We developed these micelles as efficient nanocarriers for oral drug delivery. Our model drug is celecoxib, an anti-inflammatory hydrophobic drug utilized for treatment of rheumatoid arthritis and osteoarthritis, now also evaluated as a potent anticancer drug. This system is unique as it enables encapsulation loads >100-fold higher than other β-casein/drug formulations, and does not require additives as do other formulations that have high loadings. This is combined with the ability to lyophilize the formulation without a cryoprotectant, long-term physical and chemical stability of the resulting powder, and fully reversible reconstitution of the structures by rehydration. The dry dosage form, in which >95% of the drug is encapsulated, meets the daily dose. Cryo-TEM and DLS prove that drug encapsulation results in micelle swelling, and X-ray diffraction shows that the encapsulated drug is amorphous. Altogether, our novel dosage form is highly advantageous for oral administration. Copyright © 2012 Elsevier B.V. All rights reserved.

Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

PubMed Central

Massadeh, Salam; Alaamery, Manal; Al-Qatanani, Shatha; Alarifi, Saqer; Bawazeer, Shahad; Alyafee, Yusra

2016-01-01

Background PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic). In this study, methotrexate (MTX)-loaded nanoparticles were prepared by the double emulsion method. Method Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol) as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%). Results Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

Drug loading and release on tumor cells using silk fibroin-albumin nanoparticles as carriers

NASA Astrophysics Data System (ADS)

Subia, B.; Kundu, S. C.

2013-01-01

Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin-albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin-albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules.

A Comparative Cytotoxic Evaluation of Disulfiram Encapsulated PLGA Nanoparticles on MCF-7 Cells.

PubMed

Fasehee, Hamidreza; Ghavamzadeh, Ardeshir; Alimoghaddam, Kamran; Ghaffari, Seyed-Hamidollah; Faghihi, Shahab

2017-04-01

Background: Disulfiram is oral aldehyde dehydrogenase (ALDH) inhibitor that has been used in the treatment of alcoholism. Recent studies show that this drug has anticancer properties; however, its rapid degradation has limited its clinical application. Encapsulation of disulfiram polymeric nanoparticles (NPs) may improve its anticancer activities and protect rapid degradation of the drug. Materials and Methods: A poly (lactide-co-Glycolide) (PLGA) was developed for encapsulation of disulfiram and its delivery into breast cancer cells. Disulfiram encapsulated PLGA NPs were prepared by nanoprecipitation method and were characterized by Scanning Electron Microscopy (SEM). The loading and encapsulation efficiency of NPs were determined using UV-Visible spectroscopy. Cell cytotoxicity of free and encapsulated form of disulfiram is also determined using MTT assay. Results: Disulfiram encapsulated PLGA NPs had uniform size with 165 nm. Drug loading and entrapment efficiency were 5.35 ±0.03% and 58.85±1.01%. The results of MTT assay showed that disulfiram encapsulated PLGA NPs were more potent in induction of apoptosis compare to free disulfiram. Conclusion: Based on the results obtained in the present study it can be concluded that encapsulation of disulfiram with PLGA can protect its degradation in improve its cytotoxicity on breast cancer cells.

Enhanced encapsulation of metoprolol tartrate with carbon nanotubes as adsorbent

NASA Astrophysics Data System (ADS)

Garala, Kevin; Patel, Jaydeep; Patel, Anjali; Dharamsi, Abhay

2011-12-01

A highly water-soluble antihypertensive drug, metoprolol tartrate (MT), was selected as a model drug for preparation of multi-walled carbon nanotubes (MWCNTs)-impregnated ethyl cellulose (EC) microspheres. The present investigation was aimed to increase encapsulation efficiency of MT with excellent adsorbent properties of MWCNTs. The unique surface area, stiffness, strength and resilience of MWCNTs have drawn much anticipation as carrier for highly water-soluble drugs. Carbon nanotubes drug adsorbate (MWCNTs:MT)-loaded EC microspheres were further optimized by the central composite design of the experiment. The effects of independent variables (MWCNTs:MT and EC:adsorbate) were evaluated on responses like entrapment efficiency (EE) and t 50 (time required for 50% drug release). The optimized batch was compared with drug alone EC microspheres. The results revealed high degree of improvement in encapsulation efficiency for MWCNTs:MT-loaded EC microspheres. In vitro drug release study exhibited complete release form drug alone microspheres within 15 h, while by the same time only 50-60% drug was released for MWCNTs-impregnated EC microspheres. The optimized batch was further characterized by various instrumental analyses such as scanning electron microscopy, powder X-ray diffraction and differential scanning calorimetry. The results endorse encapsulation of MWCNTs:MT adsorbate inside the matrix of EC microspheres, which might have resulted in enhanced encapsulation and sustained effect of MT. Hence, MWCNTs can be utilized as novel carriers for extended drug release and enhanced encapsulation of highly water-soluble drug, MT.

Preparation and optimization of chlorophene-loaded nanospheres as controlled release antimicrobial delivery systems.

PubMed

Phuengkham, Hathaichanok; Teeranachaideekul, Veerawat; Chulasiri, Malyn; Nasongkla, Norased

2016-01-01

Chlorophene-loaded nanospheres with various formulation parameters were evaluated. The optimal formulation was found at 0.1% w/v of poloxamer 407, 15 mL of ethyl acetate and 20% initial chlorophene loading that provided the suitable size (179 nm), the highest loading content (19.2%), encapsulation efficiency (88.0%) and yield (91.6%). Moreover, encapsulation of chlorophene in nanospheres was able to prolong and sustain drug release over one month. Chlorophene-loaded nanospheres were effective against Staphylococcus aureus (S. aureus) and Candida albicans (C. albicans), the main cause of hospital-acquired infections. Chlorophene-loaded nanospheres were effective against S. aureus (>46 µg/mL) and C. albicans (>184 µg/mL). These nanospheres appeared to have profound effect on the time-dependent hemolytic activity due to gradual release of chlorophene. At the concentration of 46 µg/mL, nearly no HRBC hemolysis in 24 h compared to 80% of hemolysis from free drug. In conclusion, polymeric nanospheres were successfully fabricated to encapsulate chlorophene which can eliminate inherent toxicity of drugs and have potential uses in prolonged release of antimicrobial.

Drug-loaded poly (ε-caprolactone)/Fe3O4 composite microspheres for magnetic resonance imaging and controlled drug delivery

NASA Astrophysics Data System (ADS)

Wang, Guangshuo; Zhao, Dexing; Li, Nannan; Wang, Xuehan; Ma, Yingying

2018-06-01

In this study, poly (ε-caprolactone) (PCL) microspheres loading magnetic Fe3O4 nanoparticles and anti-cancer drug of doxorubicin hydrochloride (DOX) were successfully prepared by a modified solvent-evaporation method. The obtained magnetic composite microspheres exhibited dual features of magnetic resonance imaging and controlled drug delivery. The morphology, structure, thermal behavior and magnetic properties of the drug-loaded magnetic microspheres were investigated in detail by SEM, XRD, DSC and SQUID. The obtained composite microspheres showed superparamagnetic behavior and T2-weighted enhancement effect. The drug loading, encapsulation efficiency, releasing behavior and in vitro cytotoxicity of the drug-loaded composite microspheres were systematically investigated. It was found that the values of drug loading and encapsulation efficiency were 36.7% and 25.8%, respectively. The composite microspheres were sensitive to pH and released in a sustained way, and both the release curves under various pH conditions (4.0 and 7.4) were well satisfied with the biphase kinetics function. In addition, the magnetic response of the drug-loaded microspheres was studied and the results showed that the composite microspheres had a good magnetic stability and strong targeting ability.

Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes

PubMed Central

Panwar, Preety; Pandey, Bhumika; Lakhera, P C; Singh, K P

2010-01-01

The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was encapsulated in nanosize liposomes. Rapid evaporation method was used for the preparation of albendazole-encapsulated conventional and PEGylated liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (6:4) and PC:CH: polyethylene glycol (PEG) (5:4:1), respectively. In this study, PEGylated and conventional liposomes containing albendazole were prepared and their characteristics, such as particle size, encapsulation efficiency, and in vitro drug release were investigated. The drug encapsulation efficiency of PEGylated and conventional liposomes was 81% and 72%, respectively. The biophysical characterization of both conventional and PEG-coated liposomes were done by transmission electron microscopy and UV-vis spectrophotometry. Efforts were made to study in vitro release of albendazole. The drug release rate showed decrease in albendazole release in descending order: free albendazole, albendazole-loaded conventional liposomes, and least with albendazole-loaded PEG-liposomes. Biologically relevant vesicles were prepared and in vitro release of liposome-entrapped albendazole was determined. PMID:20309396

A Comparative Cytotoxic Evaluation of Disulfiram Encapsulated PLGA Nanoparticles on MCF-7 Cells

PubMed Central

Fasehee, Hamidreza; Ghavamzadeh, Ardeshir; Alimoghaddam, Kamran; Ghaffari, Seyed-Hamidollah; Faghihi, Shahab

2017-01-01

Background: Disulfiram is oral aldehyde dehydrogenase (ALDH) inhibitor that has been used in the treatment of alcoholism. Recent studies show that this drug has anticancer properties; however, its rapid degradation has limited its clinical application. Encapsulation of disulfiram polymeric nanoparticles (NPs) may improve its anticancer activities and protect rapid degradation of the drug. Materials and Methods: A poly (lactide-co-Glycolide) (PLGA) was developed for encapsulation of disulfiram and its delivery into breast cancer cells. Disulfiram encapsulated PLGA NPs were prepared by nanoprecipitation method and were characterized by Scanning Electron Microscopy (SEM). The loading and encapsulation efficiency of NPs were determined using UV-Visible spectroscopy. Cell cytotoxicity of free and encapsulated form of disulfiram is also determined using MTT assay. Results: Disulfiram encapsulated PLGA NPs had uniform size with 165 nm. Drug loading and entrapment efficiency were 5.35 ±0.03% and 58.85±1.01%. The results of MTT assay showed that disulfiram encapsulated PLGA NPs were more potent in induction of apoptosis compare to free disulfiram. Conclusion: Based on the results obtained in the present study it can be concluded that encapsulation of disulfiram with PLGA can protect its degradation in improve its cytotoxicity on breast cancer cells. PMID:28875004

Galantamine-loaded PLGA nanoparticles, from nano-emulsion templating, as novel advanced drug delivery systems to treat neurodegenerative diseases

NASA Astrophysics Data System (ADS)

Fornaguera, C.; Feiner-Gracia, N.; Calderó, G.; García-Celma, M. J.; Solans, C.

2015-07-01

Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases.Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03474d

Enhanced encapsulation and bioavailability of breviscapine in PLGA microparticles by nanocrystal and water-soluble polymer template techniques.

PubMed

Wang, Hong; Zhang, Guangxing; Ma, Xueqin; Liu, Yanhua; Feng, Jun; Park, Kinam; Wang, Wenping

2017-06-01

Poly (lactide-co-glycolide) (PLGA) microparticles are widely used for controlled drug delivery. Emulsion methods have been commonly used for preparation of PLGA microparticles, but they usually result in low loading capacity, especially for drugs with poor solubility in organic solvents. In the present study, the nanocrystal technology and a water-soluble polymer template method were used to fabricate nanocrystal-loaded microparticles with improved drug loading and encapsulation efficiency for prolonged delivery of breviscapine. Breviscapine nanocrystals were prepared using a precipitation-ultrasonication method and further loaded into PLGA microparticles by casting in a mold from a water-soluble polymer. The obtained disc-like particles were then characterized and compared with the spherical particles prepared by an emulsion-solvent evaporation method. X-ray powder diffraction (XRPD) and confocal laser scanning microscopy (CLSM) analysis confirmed a highly-dispersed state of breviscapine inside the microparticles. The drug form, loading percentage and fabrication techniques significantly affected the loading capacity and efficiency of breviscapine in PLGA microparticles, and their release performance as well. Drug loading was increased from 2.4% up to 15.3% when both nanocrystal and template methods were applied, and encapsulation efficiency increased from 48.5% to 91.9%. But loading efficiency was reduced as the drug loading was increased. All microparticles showed an initial burst release, and then a slow release period of 28days followed by an erosion-accelerated release phase, which provides a sustained delivery of breviscapine over a month. A relatively stable serum drug level for more than 30days was observed after intramuscular injection of microparticles in rats. Therefore, PLGA microparticles loaded with nanocrystals of poorly soluble drugs provided a promising approach for long-term therapeutic products characterized with preferable in vitro and in vivo performance. Copyright © 2017 Elsevier B.V. All rights reserved.

Facile Preparation of Drug-Loaded Tristearin Encapsulated Superparamagnetic Iron Oxide Nanoparticles Using Coaxial Electrospray Processing.

PubMed

Rasekh, Manoochehr; Ahmad, Zeeshan; Cross, Richard; Hernández-Gil, Javier; Wilton-Ely, James D E T; Miller, Philip W

2017-06-05

Naturally occurring polymers are promising biocompatible materials that have many applications for emerging therapies, drug delivery systems, and diagnostic agents. The handling and processing of such materials still constitutes a major challenge, which can limit the full exploitation of their properties. This study explores an ambient environment processing technique: coaxial electrospray (CO-ES) to encapsulate genistein (an isoflavonoid and model drug), superparamagnetic iron oxide nanoparticles (SPIONs, 10-15 nm), and a fluorophore (BODIPY) into a layered (triglyceride tristearin shell) particulate system, with a view to constructing a theranostic agent. Mode mapping of CO-ES led to an optimized atomization engineering window for stable jetting, leading to encapsulation of SPIONs within particles of diameter 0.65-1.2 μm and drug encapsulation efficiencies of around 92%. Electron microscopy was used to image the encapsulated SPIONs and confirm core-shell triglyceride encapsulation in addition to further physicochemical characterization (AFM, FTIR, DSC, and TGA). Cell viability assays (MTT, HeLa cells) were used to determine optimal SPION loaded particles (∼1 mg/mL), while in vitro release profile experiments (PBS, pH = 7.4) demonstrate a triphasic release profile. Further cell studies confirmed cell uptake and internalization at selected time points (t = 1, 2, and 4 h). The results suggest potential for using the CO-ES technique as an efficient way to encapsulate SPIONs together with sensitive drugs for the development of multimodal particles that have potential application for combined imaging and therapy.

RBC micromotors carrying multiple cargos towards potential theranostic applications

NASA Astrophysics Data System (ADS)

Wu, Zhiguang; Esteban-Fernández de Ávila, Berta; Martín, Aída; Christianson, Caleb; Gao, Weiwei; Thamphiwatana, Soracha Kun; Escarpa, Alberto; He, Qiang; Zhang, Liangfang; Wang, Joseph

2015-08-01

Red blood cell (RBC)-based micromotors containing both therapeutic and diagnostic modalities are described as a means for potential theranostic applications. In this natural RBC-based multicargo-loaded micromotor system, quantum dots (QDs), anti-cancer drug doxorubicin (DOX), and magnetic nanoparticles (MNPs), were co-encapsulated into RBC micromotors. The fluorescent emission of both QDs and DOX provides direct visualization of their loading inside the RBC motors at two distinct wavelengths. The presence of MNPs within the RBCs allows for efficient magnetic guidance under ultrasound propulsion along with providing the potential for magnetic resonance imaging. The simultaneous encapsulation of the imaging nanoparticles and therapeutic payloads within the same RBC micromotor has a minimal effect upon its propulsion behavior. The ability of the RBC micromotors to transport imaging and therapeutic agents at high speed and spatial precision through a complex microchannel network is also demonstrated. Such ability to load and transport diagnostic imaging agents and therapeutic drugs within a single cell-based motor, in addition to a lower toxicity observed once the drug is encapsulated within the multicargo RBC motor, opens the door to the development of theranostic micromotors that may simultaneously treat and monitor diseases.Red blood cell (RBC)-based micromotors containing both therapeutic and diagnostic modalities are described as a means for potential theranostic applications. In this natural RBC-based multicargo-loaded micromotor system, quantum dots (QDs), anti-cancer drug doxorubicin (DOX), and magnetic nanoparticles (MNPs), were co-encapsulated into RBC micromotors. The fluorescent emission of both QDs and DOX provides direct visualization of their loading inside the RBC motors at two distinct wavelengths. The presence of MNPs within the RBCs allows for efficient magnetic guidance under ultrasound propulsion along with providing the potential for magnetic resonance imaging. The simultaneous encapsulation of the imaging nanoparticles and therapeutic payloads within the same RBC micromotor has a minimal effect upon its propulsion behavior. The ability of the RBC micromotors to transport imaging and therapeutic agents at high speed and spatial precision through a complex microchannel network is also demonstrated. Such ability to load and transport diagnostic imaging agents and therapeutic drugs within a single cell-based motor, in addition to a lower toxicity observed once the drug is encapsulated within the multicargo RBC motor, opens the door to the development of theranostic micromotors that may simultaneously treat and monitor diseases. Electronic supplementary information (ESI) available: Videos of the propulsion of the multicargo-loaded, RBC-based micromotors and more data are available in the ESI. See DOI: 10.1039/c5nr03730a

Brain-Targeted Delivery of Trans-Activating Transcriptor-Conjugated Magnetic PLGA/Lipid Nanoparticles

PubMed Central

Zhang, Yifang; Sun, Tingting; Zhang, Fang; Wu, Jian; Fu, Yanyan; Du, Yang; Zhang, Lei; Sun, Ying; Liu, YongHai; Ma, Kai; Liu, Hongzhi; Song, Yuanjian

2014-01-01

Magnetic poly (D,L-lactide-co-glycolide) (PLGA)/lipid nanoparticles (MPLs) were fabricated from PLGA, L-α-phosphatidylethanolamine (DOPE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-amino (polyethylene glycol) (DSPE-PEG-NH2), and magnetic nanoparticles (NPs), and then conjugated to trans-activating transcriptor (TAT) peptide. The TAT-MPLs were designed to target the brain by magnetic guidance and TAT conjugation. The drugs hesperidin (HES), naringin (NAR), and glutathione (GSH) were encapsulated in MPLs with drug loading capacity (>10%) and drug encapsulation efficiency (>90%). The therapeutic efficacy of the drug-loaded TAT-MPLs in bEnd.3 cells was compared with that of drug-loaded MPLs. The cells accumulated higher levels of TAT-MPLs than MPLs. In addition, the accumulation of QD-loaded fluorescein isothiocyanate (FITC)-labeled TAT-MPLs in bEnd.3 cells was dose and time dependent. Our results show that TAT-conjugated MPLs may function as an effective drug delivery system that crosses the blood brain barrier to the brain. PMID:25187980

Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticles.

PubMed

Wen, Xiangru; Wang, Kai; Zhao, Ziming; Zhang, Yifang; Sun, Tingting; Zhang, Fang; Wu, Jian; Fu, Yanyan; Du, Yang; Zhang, Lei; Sun, Ying; Liu, YongHai; Ma, Kai; Liu, Hongzhi; Song, Yuanjian

2014-01-01

Magnetic poly (D,L-lactide-co-glycolide) (PLGA)/lipid nanoparticles (MPLs) were fabricated from PLGA, L-α-phosphatidylethanolamine (DOPE), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-amino (polyethylene glycol) (DSPE-PEG-NH2), and magnetic nanoparticles (NPs), and then conjugated to trans-activating transcriptor (TAT) peptide. The TAT-MPLs were designed to target the brain by magnetic guidance and TAT conjugation. The drugs hesperidin (HES), naringin (NAR), and glutathione (GSH) were encapsulated in MPLs with drug loading capacity (>10%) and drug encapsulation efficiency (>90%). The therapeutic efficacy of the drug-loaded TAT-MPLs in bEnd.3 cells was compared with that of drug-loaded MPLs. The cells accumulated higher levels of TAT-MPLs than MPLs. In addition, the accumulation of QD-loaded fluorescein isothiocyanate (FITC)-labeled TAT-MPLs in bEnd.3 cells was dose and time dependent. Our results show that TAT-conjugated MPLs may function as an effective drug delivery system that crosses the blood brain barrier to the brain.

Enhanced skin penetration of lidocaine through encapsulation into nanoethosomes and nanostructured lipid carriers: a comparative study.

PubMed

Babaei, S; Ghanbarzadeh, S; Adib, Z M; Kouhsoltani, M; Davaran, S; Hamishehkar, H

2016-05-01

Lipid based nanoparticles have become a major research object in topical drug delivery to enable drugs to pass the stratum corneum and reach the desired skin layer. The present investigation deals with the encapsulation of lidoacine into nanostructured lipid carriers (NLCs) and nanoethosomes for improving its dermal delivery and consequently local anesthetic efficacy. Concurrently these two topical delivery systems were compared. Lidocaine-loaded NLCs and nanoethosomes were characterized by various techniques and used for an in vitro skin penetration study using excised rat skin and Franz diffusion cells. The nanoparticles were tracked in the skin by following the Rhodamine-labled nanocarriers under fluorescent microscopy. Optimized lidocaine-loaded NLCs (size 96 nm, zeta potential -13.7 mV, encapsulation efficiency (EE) % 69.86% and loading capacity (LC) % 10.47%) and nanoethosomes (size 105.4 nm, zeta potential -33.6 mV, EE 40.14% and LC 8.02%) were chosen for a skin drug delivery study. Higher skin drug deposition of NLCs and nanoethosomal formulations compared to lidocaine hydroalcoholic solution represented a better localization of the drug in the skin. NLC formulation showed the lowest entered drug in the receptor phase of Franz diffusion cell in comparison with nanoethosomes and hydroalcoholic solution confirming the highest skin accumulation of drug. Both colloidal systems showed superiority over the drug solution for dermal delivery of lidocaine, however, NLC exhibited more promising characteristics than nanoethosomes regarding drug loading and skin targeted delivery.

Preparation and characterization of isoniazid-loaded crude soybean lecithin liposomes.

PubMed

Nkanga, Christian Isalomboto; Krause, Rui Werner; Noundou, Xavier Siwe; Walker, Roderick Bryan

2017-06-30

Tuberculosis (TB) is a poverty related infectious disease that is rapidly giving rise to public health concerns. Lengthy drug administration and frequent adverse side-effects associated with TB treatment make anti-tubercular drugs (ATDs) good candidates for drug delivery studies. This work aimed to formulate and prepare liposomes as a cost-effective option for ATD delivery. Liposomes were prepared by film hydration using crude soybean lecithin (CL) and not pure phospholipids as in the normal practice. Cholesterol was also used (up to 25% mass ratio), and isoniazid (INH) was encapsulated as model drug using a freeze-thaw loading technique. Purified soybean lecithin (PL) was also used for comparative purposes, under the same conditions. INH-loaded liposomes were characterized for particle size, Zeta Potential (ZP), encapsulation efficiency (EE) and drug release. Physicochemical properties were investigated using thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction and Fourier transform infrared. INH-loaded CL-based liposomes showed high EE (79±2.45%). The average particle size (813.00±9.21nm) and ZP (-42.80±4.31mV) of this formulation are promising for the treatment of TB by pulmonary delivery. These findings suggest the possibility of encapsulating ATDs in liposomes made of crude soybean lecithin that is cheap and readily available. Copyright © 2017 Elsevier B.V. All rights reserved.

Formulation, characterization and cytotoxicity studies of alendronate sodium-loaded solid lipid nanoparticles.

PubMed

Ezzati Nazhad Dolatabadi, Jafar; Hamishehkar, Hamed; Eskandani, Morteza; Valizadeh, Hadi

2014-05-01

Solid lipid nanoparticles (SLNs) are novel drug delivery system for drug targeting in various routs of administration such as parenteral, oral, ophthalmic and topical. These carriers have some advantages such as high drug payload, increased drug stability, the possibility of incorporation of lipophilic and hydrophilic drugs, and low biotoxicity. In this study, alendronate sodium was used as a hydrophilic model drug and was incorporated into SLNs. Hot homogenization method was used for preparation of alendronate sodium-loaded SLN formulations and the encapsulation efficiency of drug in SLNs was determined by ultrafiltration method using centrifugal devices. Scanning electron microscopy (SEM) was carried out to study the morphological behaviors of prepared SLNs like sphericity. Several cytotoxicity studies including MTT, DAPI staining and DNA fragmentation assays were used for biocompatibility assays. High drug encapsulation efficiency (70-85%) was achieved by drug determination through derivatization with o-phthalaldehyde. The physical stability of drug-loaded SLNs in aqueous dispersions was assessed in terms of size and drug leakage during two weeks. Scanning electron microscopy images showed spherical particles in the nanometer range confirming the obtained data from size analyzer. Several cytotoxicity studies including MTT, DAPI staining and DNA fragmentation assays as well as flow cytometry analysis confirmed the low toxicity of alendronate-loaded SLNs. The cost-efficient procedure, the avoidance of organic solvents application, acceptable reproducibility, ease of manufacturing under mild preparation conditions, high level of drug encapsulation, desirable physical stability and biocompatibility are the advantages of the proposed SLN formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

Mechanical properties of drug loaded diblock copolymer bilayers: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Grillo, Damián A.; Albano, Juan M. R.; Mocskos, Esteban E.; Facelli, Julio C.; Pickholz, Mónica; Ferraro, Marta B.

2018-06-01

In this work, we present results of coarse-grained simulations to study the encapsulation of prilocaine (PLC), both neutral and protonated, on copolymer bilayers through molecular dynamics simulations. Using a previously validated membrane model, we have simulated loaded bilayers at different drug concentrations and at low (protonated PLC) and high (neutral PLC) pH levels. We have characterized key structural parameters of the loaded bilayers in order to understand the effects of encapsulation of PLC on the bilayer structure and mechanical properties. Neutral PLC was encapsulated in the hydrophobic region leading to a thickness increase, while the protonated species partitioned between the water phase and the poly(ethylene oxide)-poly(butadiene) (PBD) interface, relaxing the PBD region and leading to a decrease in the thickness. The tangential pressures of the studied systems were calculated, and their components were decomposed in order to gain insights on their compensation. In all cases, it is observed that the loading of the membrane does not significantly decrease the stability of the bilayer, indicating that the system could be used for drug delivery.

Mechanical properties of drug loaded diblock copolymer bilayers: A molecular dynamics study.

PubMed

Grillo, Damián A; Albano, Juan M R; Mocskos, Esteban E; Facelli, Julio C; Pickholz, Mónica; Ferraro, Marta B

2018-06-07

In this work, we present results of coarse-grained simulations to study the encapsulation of prilocaine (PLC), both neutral and protonated, on copolymer bilayers through molecular dynamics simulations. Using a previously validated membrane model, we have simulated loaded bilayers at different drug concentrations and at low (protonated PLC) and high (neutral PLC) pH levels. We have characterized key structural parameters of the loaded bilayers in order to understand the effects of encapsulation of PLC on the bilayer structure and mechanical properties. Neutral PLC was encapsulated in the hydrophobic region leading to a thickness increase, while the protonated species partitioned between the water phase and the poly(ethylene oxide)-poly(butadiene) (PBD) interface, relaxing the PBD region and leading to a decrease in the thickness. The tangential pressures of the studied systems were calculated, and their components were decomposed in order to gain insights on their compensation. In all cases, it is observed that the loading of the membrane does not significantly decrease the stability of the bilayer, indicating that the system could be used for drug delivery.

Dual drug-loaded nanoparticles on self-integrated scaffold for controlled delivery

PubMed Central

Bennet, Devasier; Marimuthu, Mohana; Kim, Sanghyo; An, Jeongho

2012-01-01

Antioxidant (quercetin) and hypoglycemic (voglibose) drug-loaded poly-D,L-lactideco-glycolide nanoparticles were successfully synthesized using the solvent evaporation method. The dual drug-loaded nanoparticles were incorporated into a scaffold film using a solvent casting method, creating a controlled transdermal drug-delivery system. Key features of the film formulation were achieved utilizing several ratios of excipients, including polyvinyl alcohol, polyethylene glycol, hyaluronic acid, xylitol, and alginate. The scaffold film showed superior encapsulation capability and swelling properties, with various potential applications, eg, the treatment of diabetes-associated complications. Structural and light scattering characterization confirmed a spherical shape and a mean particle size distribution of 41.3 nm for nanoparticles in the scaffold film. Spectroscopy revealed a stable polymer structure before and after encapsulation. The thermoresponsive swelling properties of the film were evaluated according to temperature and pH. Scaffold films incorporating dual drug-loaded nanoparticles showed remarkably high thermoresponsivity, cell compatibility, and ex vivo drug-release behavior. In addition, the hybrid film formulation showed enhanced cell adhesion and proliferation. These dual drug-loaded nanoparticles incorporated into a scaffold film may be promising for development into a transdermal drug-delivery system. PMID:22888222

Encapsulation of anticancer drug copper bis(8-hydroxyquinoline) in hydroxyapatite for pH-sensitive targeted delivery and slow release.

PubMed

Weerasuriya, D R K; Wijesinghe, W P S L; Rajapakse, R M G

2017-02-01

There is a conspicuous progress in increasing anticancer drug delivery through the utilization of nanoparticles (NPs) as drug delivery agents. Hydroxyapatite (HA) gives improved clinical effectiveness of drugs by reducing systemic toxicity and broadening the spectrum of drug delivery since it is biocompatible and it can be targeted towards tumor cells. Herein, investigation of the potential of enhancing controlled drug release of the template model drug, copper bis-(8-hydroxyquinoline), by encapsulating it in hollow hydroxyapatite nano-carriers, is presented. Hydroxyapatite nanoparticles are synthesized by following four different routes to optimize its efficacy of drug loading. Copper bis-(8-hydroxyquinoline) is encapsulated by Method (a) which was effected by stirring the model drug and porous HA NPs in colloidal solution and Method (b) which was done during synthesis of hydroxyapatite nanoparticles in a solution of the model drug. In synthesizing nanoporous HA NPs, calcium carbonate is used as a template to create voids in HA. In each method, Ca/P ratio was ensured to be kept at 1.67:1. Appealing results are reported for the encapsulated product which was prepared by Method (a2). Method (a) was done at three different molar ratios of PO 4 3- :CO 3 2- and best result was obtained for that utilized 2.003:1 molar ratio (Method (a2).). It produced 98.67% of encapsulation efficiency and 2.9522mg/g of drug loading capacity. Release kinetics was studied at a range of pH values; the lower the pH of the medium the higher is the drug release. For instance, when considering the product which exhibited high encapsulation efficiency and high drug loading capacity, at pH3.5 during the first 8h it elicited about 13% of release, at pH5.0 about 8% release while at pH6.0 it was just 2.5%. During the 24-hour span, pH3.5 exhibited about 23.8%, at pH5.0 approximately 9% with an increasing trend of release and at pH6.0 showed a value just above 2.5%. As such, acidity of the cancerous cells can be made use to increase the drug slow-release kinetics at the vicinity of the cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Stepwise encapsulation and controlled two-stage release system for cis-Diamminediiodoplatinum

PubMed Central

Chen, Yun; Li, Qian; Wu, Qingsheng

2014-01-01

cis-Diamminediiodoplatinum (cis-DIDP) is a cisplatin-like anticancer drug with higher anticancer activity, but lower stability and price than cisplatin. In this study, a cis-DIDP carrier system based on micro-sized stearic acid was prepared by an emulsion solvent evaporation method. The maximum drug loading capacity of cis-DIDP-loaded solid lipid nanoparticles was 22.03%, and their encapsulation efficiency was 97.24%. In vitro drug release in phosphate-buffered saline (pH =7.4) at 37.5°C exhibited a unique two-stage process, which could prove beneficial for patients with tumors and malignancies. MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay results showed that cis-DIDP released from cis-DIDP-loaded solid lipid nanoparticles had better inhibition activity than cis-DIDP that had not been loaded. PMID:25061294

Microwave-assisted microemulsion technique for production of miconazole nitrate- and econazole nitrate-loaded solid lipid nanoparticles.

PubMed

Shah, Rohan M; Eldridge, Daniel S; Palombo, Enzo A; Harding, Ian H

2017-08-01

The microwave-assisted production of solid lipid nanoparticles (SLNs) is a novel technique reported recently by our group. The small particle size, solid nature and use of physiologically well-tolerated lipid materials make SLNs an interesting and potentially efficacious drug carrier. The main purpose of this research work was to investigate the suitability of microwave-assisted microemulsion technique to encapsulate selected ionic drug substances such as miconazole nitrate and econazole nitrate. The microwave-produced SLNs had a small size (250-300nm), low polydispersity (<0.20), high encapsulation efficiency (72-87%) and loading capacity (3.6-4.3%). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies suggested reduced crystallinity of stearic acid in SLNs. The release studies demonstrated a slow, sustained but incomplete release of drugs (<60% after 24h) from microwave-produced SLNs. Data fitting of drug release data revealed that the release of both drugs from microwave-produced SLNs was governed by non-Fickian diffusion indicating that drug release was both diffusion- and dissolution- controlled. Anti-fungal efficacy of drug-loaded SLNs was evaluated on C. albicans. The cell viability studies showed that cytotoxicity of SLNs was concentration-dependent. These encouraging results suggest that the microwave-assisted procedure is suitable for encapsulation of ionic drugs and that microwave-produced SLNs can act as potential carriers of antifungal drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique.

PubMed

Patel, Meghavi N; Lakkadwala, Sushant; Majrad, Mohamed S; Injeti, Elisha R; Gollmer, Steven M; Shah, Zahoor A; Boddu, Sai Hanuman Sagar; Nesamony, Jerry

2014-12-01

The aim of this research was to advance solid lipid nanoparticle (SLN) preparation methodology by preparing glyceryl monostearate (GMS) nanoparticles using a temperature-modulated solidification process. The technique was reproducible and prepared nanoparticles without the need of organic solvents. An anticancer agent, 5-fluorouracil (5-FU), was incorporated in the SLNs. The SLNs were characterized by particle size analysis, zeta potential analysis, differential scanning calorimetry (DSC), infrared spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), drug encapsulation efficiency, in vitro drug release, and in vitro cell viability studies. Particle size of the SLN dispersion was below 100 nm, and that of redispersed lyophilizates was ~500 nm. DSC and infrared spectroscopy suggested that the degree of crystallinity did not decrease appreciably when compared to GMS. TEM and AFM images showed well-defined spherical to oval particles. The drug encapsulation efficiency was found to be approximately 46%. In vitro drug release studies showed that 80% of the encapsulated drug was released within 1 h. In vitro cell cultures were biocompatible with blank SLNs but demonstrated concentration-dependent changes in cell viability to 5-FU-loaded SLNs. The 5-FU-loaded SLNs can potentially be utilized in an anticancer drug delivery system.

Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy.

PubMed

Eloy, Josimar O; Petrilli, Raquel; Topan, José Fernando; Antonio, Heriton Marcelo Ribeiro; Barcellos, Juliana Palma Abriata; Chesca, Deise L; Serafini, Luciano Neder; Tiezzi, Daniel G; Lee, Robert J; Marchetti, Juliana Maldonado

2016-05-01

Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin. Copyright © 2016 Elsevier B.V. All rights reserved.

Polymeric nano-encapsulation of 5-fluorouracil enhances anti-cancer activity and ameliorates side effects in solid Ehrlich Carcinoma-bearing mice.

PubMed

Haggag, Yusuf A; Osman, Mohamed A; El-Gizawy, Sanaa A; Goda, Ahmed E; Shamloula, Maha M; Faheem, Ahmed M; McCarron, Paul A

2018-05-29

Biodegradable PLGA nanoparticles, loaded with 5-fluorouracil (5FU), were prepared using a double emulsion method and characterised in terms of mean diameter, zeta potential, entrapment efficiency and in vitro release. Poly (vinyl alcohol) was used to modify both internal and external aqueous phases and shown have a significant effect on nanoparticulate size, encapsulation efficiency and the initial burst release. Addition of poly (ethylene glycol) to the particle matrix, as part of the polymeric backbone, improved significantly the encapsulation efficiency. 5FU-loaded NPs were spherical in shape and negatively charged with a size range of 185-350 nm. Biological evaluation was performed in vivo using a solid Ehrlich carcinoma (SEC) murine model. An optimised 5FU-loaded formulation containing PEG as part of a block copolymer induced a pronounced reduction in tumour volume and tumour weight, together with an improved percentage tumour growth inhibition. Drug-loaded nanoparticles showed no significant toxicity or associated changes on liver and kidney function in tested animals, whereas increased alanine aminotransferase, aspartate aminotransferase and serum creatinine were observed in animals treated with free 5FU. Histopathological examination demonstrated enhanced cytotoxic action of 5FU-loaded nanoparticles when compared to the free drug. Based on these findings, it was concluded that nano-encapsulation of 5FU using PEGylated PLGA improved encapsulation and sustained in vitro release. This leads to increased anti-tumour efficacy against SEC, with a reduction in adverse effects. Published by Elsevier Masson SAS.

Nano-aggregates: emerging delivery tools for tumor therapy.

PubMed

Sharma, Vinod Kumar; Jain, Ankit; Soni, Vandana

2013-01-01

A plethora of formulation techniques have been reported in the literature for site-specific targeting of water-soluble and -insoluble anticancer drugs. Along with other vesicular and particulate carrier systems, nano-aggregates have recently emerged as a novel supramolecular colloidal carrier with promise for using poorly water-soluble drugs in molecular targeted therapies. Nano-aggregates possess some inherent properties such as size in the nanometers, high loading efficiency, and in vivo stability. Nano-aggregates can provide site-specific drug delivery via either a passive or active targeting mechanism. Nano-aggregates are formed from a polymer-drug conjugated amphiphilic block copolymer. They are suitable for encapsulation of poorly water-soluble drugs by covalent conjugation as well as physical encapsulation. Because of physical encapsulation, a maximum amount of drug can be loaded in nano-aggregates, which helps to achieve a sufficiently high drug concentration at the target site. Active transport can be achieved by conjugating a drug with vectors or ligands that bind specifically to receptors being overexpressed in the tumor cells. In this review, we explore synthesis and tumor targeting potential of nano-aggregates with active and passive mechanisms, and we discuss various characterization parameters, ex vivo studies, biodistribution studies, clinical trials, and patents.

Vancomycin-loaded nanobubbles: A new platform for controlled antibiotic delivery against methicillin-resistant Staphylococcus aureus infections.

PubMed

Argenziano, Monica; Banche, Giuliana; Luganini, Anna; Finesso, Nicole; Allizond, Valeria; Gulino, Giulia Rossana; Khadjavi, Amina; Spagnolo, Rita; Tullio, Vivian; Giribaldi, Giuliana; Guiot, Caterina; Cuffini, Anna Maria; Prato, Mauro; Cavalli, Roberta

2017-05-15

Vancomycin (Vm) currently represents the gold standard against methicillin-resistant Staphylococcus aureus (MRSA) infections. However, it is associated with low oral bioavailability, formulation stability issues, and severe side effects upon systemic administration. These drawbacks could be overcome by Vm topical administration if properly encapsulated in a nanocarrier. Intriguingly, nanobubbles (NBs) are responsive to physical external stimuli such as ultrasound (US), promoting drug delivery. In this work, perfluoropentane (PFP)-cored NBs were loaded with Vm by coupling to the outer dextran sulfate shell. Vm-loaded NBs (VmLNBs) displayed ∼300nm sizes, anionic surfaces and good drug encapsulation efficiency. In vitro, VmLNBs showed prolonged drug release kinetics, not accompanied by cytotoxicity on human keratinocytes. Interestingly, VmLNBs were generally more effective than Vm alone in MRSA killing, with VmLNB antibacterial activity being more sustained over time as a result of prolonged drug release profile. Besides, VmLNBs were not internalized by staphylococci, opposite to Vm solution. Further US association promoted drug delivery from VmLNBs through an in vitro model of porcine skin. Taken together, these results support the hypothesis that proper Vm encapsulation in US-responsive NBs might be a promising strategy for the topical treatment of MRSA wound infections. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system for liver cancer chemotherapy.

PubMed

Nittayacharn, Pinunta; Nasongkla, Norased

2017-07-01

The objective of this work was to develop self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system for liver cancer chemotherapy and studied the release profiles of doxorubicin (Dox) from different depot formulations. Tri-block copolymers of poly(ε-caprolactone), poly(D,L-lactide) and poly(ethylene glycol) named PLECs were successfully used as a biodegradable material to encapsulate Dox as the injectable local drug delivery system. Depot formation and encapsulation efficiency of these depots were evaluated. Results show that depots could be formed and encapsulate Dox with high drug loading content. For the release study, drug loading content (10, 15 and 20% w/w) and polymer concentration (25, 30, and 35% w/v) were varied. It could be observed that the burst release occurred within 1-2 days and this burst release could be reduced by physical mixing of hydroxypropyl-beta-cyclodextrin (HP-β-CD) into the depot system. The degradation at the surface and cross-section of the depots were examined by Scanning Electron Microscope (SEM). In addition, cytotoxicity of Dox-loaded depots and blank depots were tested against human liver cancer cell lines (HepG2). Dox released from depots significantly exhibited potent cytotoxic effect against HepG2 cell line compared to that of blank depots. Results from this study reveals an important insight in the development of injectable drug delivery system for liver cancer chemotherapy. Schematic diagram of self-forming doxorubicin-loaded polymeric depots as an injectable drug delivery system and in vitro characterizations. (a) Dox-loaded PLEC depots could be formed with more than 90% of sustained-release Dox at 25% polymer concentration and 20% Dox-loading content. The burst release occurred within 1-2 days and could be reduced by physical mixing of hydroxypropyl-beta-cyclodextrin (HP-β-CD) into the depot system. (b) Dox released from depots significantly exhibited potent cytotoxic effect against human liver cancer cell lines (HepG2 cell line) compared to that of blank depots. (c) Dox-loaded depots showed bulk erosion with hollow core at day 60.

Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

NASA Astrophysics Data System (ADS)

Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

2013-03-01

Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide- co-glycolide) (PLGA) microparticles (size 1-4 μm, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers. II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations.

PubMed

Das, Surajit; Ng, Wai Kiong; Tan, Reginald B H

2014-03-14

This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.

Self-assembled lipid--polymer hybrid nanoparticles: a robust drug delivery platform.

PubMed

Zhang, Liangfang; Chan, Juliana M; Gu, Frank X; Rhee, June-Wha; Wang, Andrew Z; Radovic-Moreno, Aleksandar F; Alexis, Frank; Langer, Robert; Farokhzad, Omid C

2008-08-01

We report the engineering of a novel lipid-polymer hybrid nanoparticle (NP) as a robust drug delivery platform, with high drug encapsulation yield, tunable and sustained drug release profile, excellent serum stability, and potential for differential targeting of cells or tissues. The NP comprises three distinct functional components: (i) a hydrophobic polymeric core where poorly water-soluble drugs can be encapsulated; (ii) a hydrophilic polymeric shell with antibiofouling properties to enhance NP stability and systemic circulation half-life; and (iii) a lipid monolayer at the interface of the core and the shell that acts as a molecular fence to promote drug retention inside the polymeric core, thereby enhancing drug encapsulation efficiency, increasing drug loading yield, and controlling drug release. The NP is prepared by self-assembly through a single-step nanoprecipitation method in a reproducible and predictable manner, making it potentially suitable for scale-up.

Self-Assembled Lipid-Polymer Hybrid Nanoparticles: A Robust Drug Delivery Platform

PubMed Central

Zhang, Liangfang; Chan, Juliana M; Gu, Frank X; Rhee, June-Wha; Wang, Andrew Z; Radovic-Moreno, Aleksandar F; Alexis, Frank; Langer, Robert; Farokhzad, Omid C

2014-01-01

We report the engineering of a novel lipid-polymer hybrid nanoparticle (NP) as a robust drug delivery platform, with high drug encapsulation yield, tunable and sustained drug release profile, excellent serum stability, and potential for differential targeting of cells or tissues. The NP is comprised of three distinct functional components: i) a hydrophobic polymeric core where poorly water-soluble drugs can be encapsulated; ii) a hydrophilic polymeric shell with anti-biofouling properties to enhance NP stability and systemic circulation half-life; and iii) a lipid monolayer at the interface of the core and the shell that acts as a molecular fence to promote drug retention inside the polymeric core, thereby enhancing drug encapsulation efficiency, increasing drug loading yield, and controlling drug release. The NP is prepared by self-assembly through a single-step nanoprecipitation method in a reproducible and predictable manner, making it potentially suitable for scale-up PMID:19206374

AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting and drug delivery.

PubMed

Aravind, Athulya; Jeyamohan, Prashanti; Nair, Remya; Veeranarayanan, Srivani; Nagaoka, Yutaka; Yoshida, Yasuhiko; Maekawa, Toru; Kumar, D Sakthi

2012-11-01

Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug-loaded PLGA-lecithin-PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). The drug-loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF-7 and GI-1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110 nm. Drug-loading studies indicated that under the same drug loading, the aptamer-targeted NPs show enhanced cancer killing effect compared to the corresponding non-targeted NPs. In addition, the PLGA-lecithin-PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer-PLGA-lecithin-PEG NPs are potential carrier candidates for differential targeted drug delivery. Copyright © 2012 Wiley Periodicals, Inc.

Sustained-releasing hollow microparticles with dual-anticancer drugs elicit greater shrinkage of tumor spheroids.

PubMed

Baek, Jong-Suep; Choo, Chee Chong; Tan, Nguan Soon; Loo, Say Chye Joachim

2017-10-06

Polymeric particulate delivery systems are vastly explored for the delivery of chemotherapeutic agents. However, the preparation of polymeric particulate systems with the capability of providing sustained release of two or more drugs is still a challenge. Herein, poly (D, L-lactic-co-glycolic acid, 50:50) hollow microparticles co-loaded with doxorubicin and paclitaxel were developed through double-emulsion solvent evaporation technique. Hollow microparticles were formed through the addition of an osmolyte into the fabrication process. The benefits of hollow over solid microparticles were found to be higher encapsulation efficiency and a more rapid drug release rate. Further modification of the hollow microparticles was accomplished through the introduction of methyl-β-cyclodextrin. With this, a higher encapsulation efficiency of both drugs and an enhanced cumulative release were achieved. Spheroid study further demonstrated that the controlled release of the drugs from the methyl-β-cyclodextrin -loaded hollow microparticles exhibited enhanced tumor regressions of MCF-7 tumor spheroids. Such hollow dual-drug-loaded hollow microparticles with sustained releasing capabilities may have a potential for future applications in cancer therapy.

Paclitaxel Encapsulated in Halloysite Clay Nanotubes for Intestinal and Intracellular Delivery.

PubMed

Yendluri, Raghuvara; Lvov, Yuri; de Villiers, Melgardt M; Vinokurov, Vladimir; Naumenko, Ekaterina; Tarasova, Evgenya; Fakhrullin, Rawil

2017-10-01

Naturally formed halloysite tubules have a length of 1 μm and lumens with a diameter of 12-15 nm which can be loaded with drugs. Halloysite's biocompatibility allows for its safe delivering to cells at a concentration of up to 0.5 mg/mL. We encapsulated the anticancer drug paclitaxel in halloysite and evaluated the drug release kinetics in simulated gastric and intestinal conditions. To facilitate maximum drug release in intestinal tract, halloysite tubes were coated with the pH-responsive polymer poly(methacrylic acid-co-methyl methacrylate). Release kinetics indicated a triggered drug release pattern at higher pH, corresponding to digestive tract environment. Tablets containing halloysite, loaded with paclitaxel, as a compression excipient were formulated with drug release occurring at a sustained rate. In vitro anticancer effects of paclitaxel-loaded halloysite nanotubes were evaluated on human cancer cells. In all the treated cell samples, polyploid nuclei of different sizes and fragmented chromatin were observed, indicating a high therapeutic effect of halloysite formulated paclitaxel. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

A numerical study of the phase behaviors of drug particle/star triblock copolymer mixtures in dilute solutions for drug carrier application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Shanhui; Tong, Chaohui; Zhu, Yuejin, E-mail: zhuyuejin@nbu.edu.cn

The complex microstructures of drug particle/ABA star triblock copolymer in dilute solutions have been investigated by a theoretical approach which combines the self-consistent field theory and the hybrid particle-field theory. Simulation results reveal that, when the volume fraction of drug particles is smaller than the saturation concentration, the drug particle encapsulation efficiency is 100%, and micelle loading capacity increases with increasing particle volume fraction. When the volume fraction of drug particles is equal to the saturation concentration, the micelles attain the biggest size, and micelle loading capacity reaches a maximum value which is independent of the copolymer volume fraction. Whenmore » the volume fraction of drug particles is more than the saturation concentration, drug particle encapsulation efficiency decreases with increasing volume fraction of drug particles. Furthermore, it is found that the saturation concentration scales linearly with the copolymer volume fraction. The above simulation results are in good agreement with experimental results.« less

Preparation, characterization, and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model

PubMed Central

Ali, Hazem; Kalashnikova, Irina; White, Mark Andrew; Sherman, Michael; Rytting, Erik

2013-01-01

The purpose of this study was to prepare dexamethasone-loaded polymeric nanoparticles and evaluate their potential for transport across human placenta. Statistical modeling and factorial design was applied to investigate the influence of process parameters on the following nanoparticle characteristics: particle size, polydispersity index, zeta potential, and drug encapsulation efficiency. Dexamethasone and nanoparticle transport was subsequently investigated using the BeWo b30 cell line, an in vitro model of human placental trophoblast cells, which represent the rate-limiting barrier for maternal-fetal transfer. Encapsulation efficiency and drug transport were determined using a validated high performance liquid chromatography method. Nanoparticle morphology and drug encapsulation were further characterized by cryo-transmission electron microscopy and X-ray diffraction, respectively. Nanoparticles prepared from poly(lactic-co-glycolic acid) were spherical, with particle sizes ranging from 140–298 nm, and encapsulation efficiency ranging from 52–89%. Nanoencapsulation enhanced the apparent permeability of dexamethasone from the maternal compartment to the fetal compartment more than 10-fold in this model. Particle size was shown to be inversely correlated with drug and nanoparticle permeability, as confirmed with fluorescently-labeled nanoparticles. These results highlight the feasibility of designing nanoparticles capable of delivering medication to the fetus, in particular, potential dexamethasone therapy for the prenatal treatment of congenital adrenal hyperplasia. PMID:23850397

Development and characterization of polymer-oil nanostructured carrier (PONC) for controlled delivery of all-trans retinoic acid (ATRA)

NASA Astrophysics Data System (ADS)

Narvekar, Mayuri M.

The commonly used PLGA-based delivery systems are often limited by their inadequate drug loading and release properties. This study reports the integration of oil into PLGA to form the prototype of a hybrid drug carrier PONC. Our primary goal is to confer the key strength of lipid-based drug carriers, i.e. efficient encapsulation of lipophilic compounds, to a PLGA system without taking away its various useful qualities. The PONC were formulated by emulsification solvent evaporation technique, which were then characterized for particle size, encapsulation efficiency, drug release and anticancer efficacy. The ATRA loaded PONC showed excellent encapsulation efficiency and release kinetics. Even after surface functionalization with PEG , controlled drug release kinetics was maintained, with 88.5% of the encapsulated ATRA released from the PEG-PONC in a uniform manner over 120 hours. It also showed favorable physicochemical properties and serum stability. PEG-PONC has demonstrated substantially superior activity over the free ATRA in ovarian cancer cells that are non-responsive to the standard chemotherapy. The newly developed PEG-PONC significantly reduced the IC50 values (p<0.05) in the chemoresistant cells in both MTT and colony formation assays. Hence, this new ATRA-nanoformulation may offer promising means for the delivery of lipophilic compounds like all-trans retinoic acid to treat highly resistant ovarian cancer.

Methotrexate loaded gellan gum microparticles for drug delivery.

PubMed

Dhanka, Mukesh; Shetty, Chaitra; Srivastava, Rohit

2018-04-15

Recently, polysaccharides based microparticles have been found to offer an attractive potential as a carrier in drug delivery field. In this study, bare gellan gum microparticles (GG MPs) and methotrexate (MTX) loaded gellan gum microparticles (MTX-GG MPs) prepared by using simple water-in-oil (W/O) emulsion solvent diffusion method. The developed microparticles (MPs) were found discretely distributed in a spherical shape. MTX has been encapsulated in microparticles with 84.8 ± 1.68% encapsulation efficiency (%EE) and 6.45 ± 0.07% loading capacity (%LC). The Fourier Transform Infrared Spectroscopy (FTIR) characterization of the MPs clearly indicated the physical encapsulation of MTX into polymeric matrix of MPs. Thermogravimetric analysis (TGA) characterization showed slightly higher thermal stability of MTX-GG MPs in comparison to the GG MPs. In vitro release study of MTX-GG MPs showed 84% drug release within 24 h. The hemolysis study of GG MPs and MTX-GG MPs on human red blood cells (RBCs) showed <1.0% hemolysis. The cell viability studies on L929 showed GG MPs, and MTX-GG MPs are biocompatible. Copyright © 2017 Elsevier B.V. All rights reserved.

RBC micromotors carrying multiple cargos towards potential theranostic applications.

PubMed

Wu, Zhiguang; Esteban-Fernández de Ávila, Berta; Martín, Aída; Christianson, Caleb; Gao, Weiwei; Thamphiwatana, Soracha Kun; Escarpa, Alberto; He, Qiang; Zhang, Liangfang; Wang, Joseph

2015-08-28

Red blood cell (RBC)-based micromotors containing both therapeutic and diagnostic modalities are described as a means for potential theranostic applications. In this natural RBC-based multicargo-loaded micromotor system, quantum dots (QDs), anti-cancer drug doxorubicin (DOX), and magnetic nanoparticles (MNPs), were co-encapsulated into RBC micromotors. The fluorescent emission of both QDs and DOX provides direct visualization of their loading inside the RBC motors at two distinct wavelengths. The presence of MNPs within the RBCs allows for efficient magnetic guidance under ultrasound propulsion along with providing the potential for magnetic resonance imaging. The simultaneous encapsulation of the imaging nanoparticles and therapeutic payloads within the same RBC micromotor has a minimal effect upon its propulsion behavior. The ability of the RBC micromotors to transport imaging and therapeutic agents at high speed and spatial precision through a complex microchannel network is also demonstrated. Such ability to load and transport diagnostic imaging agents and therapeutic drugs within a single cell-based motor, in addition to a lower toxicity observed once the drug is encapsulated within the multicargo RBC motor, opens the door to the development of theranostic micromotors that may simultaneously treat and monitor diseases.

Microgel-Encapsulated Methylene Blue for the Treatment of Breast Cancer Cells by Photodynamic Therapy

PubMed Central

Khanal, Anil; Bui, Minh-Phuong Ngoc

2014-01-01

Purpose Photodynamic therapy (PDT) is gaining increasing recognition for breast cancer treatment because it offers local selectivity and reduced toxic side effects compared to radiotherapy and chemotherapy. In PDT, photosensitizer drugs are loaded in different nanomaterials and used in combination with light exposure. However, the most representative issue with PDT is the difficulty of nanomaterials to encapsulate anticancer drugs at high doses, which results in low efficacy of the PDT treatment. Here, we proposed the development of the poly(N-isopropylacrylamide) (PNIPAM) microgel for the encapsulation of methylene blue, an anticancer drug, for its use as breast cancer treatment in MCF-7 cell line. Methods We developed biocompatible microgels based on nonfunctionalized PNIPAM and its corresponding anionically functionalized PNIPAM and polyacrylic acid (PNIPAM-co-PAA) microgel. Methylene blue was used as the photosensitizer drug because of its ability to generate toxic reactive oxygen species upon exposure to light at 664 nm. Core PNIPAM and core/shell PNIPAM-co-PAA microgels were synthesized and characterized using ultraviolet-visible spectroscopy and dynamic light scattering. The effect of methylene blue was evaluated using the MCF-7 cell line. Results Loading of methylene blue in core PNIPAM microgel was higher than that in the core/shell PNIPAM-co-PAA microgel, indicating that electrostatic interactions did not play an important role in loading a cationic drug. This behavior is probably due to the skin layer inhibiting the high uptake of drugs in the PNIPAM-co-PAA microgel. Core PNIPAM microgel effectively retained the cationic drug (i.e., methylene blue) for several hours compared to core/shell PNIPAM-co-PAA and enhanced its photodynamic efficacy in vitro more than that of free methylene blue. Conclusion Our results showed that the employment of core PNIPAM and core/shell PNIPAM-co-PAA microgels enhanced the encapsulation of methylene blue. Core PNIPAM microgel released the drug more slowly than did core/shell PNIPAM-co-PAA, and it effectively inhibited the growth of MCF-7 cells. PMID:24744793

Microgel-encapsulated methylene blue for the treatment of breast cancer cells by photodynamic therapy.

PubMed

Khanal, Anil; Bui, Minh-Phuong Ngoc; Seo, Seong S

2014-03-01

Photodynamic therapy (PDT) is gaining increasing recognition for breast cancer treatment because it offers local selectivity and reduced toxic side effects compared to radiotherapy and chemotherapy. In PDT, photosensitizer drugs are loaded in different nanomaterials and used in combination with light exposure. However, the most representative issue with PDT is the difficulty of nanomaterials to encapsulate anticancer drugs at high doses, which results in low efficacy of the PDT treatment. Here, we proposed the development of the poly(N-isopropylacrylamide) (PNIPAM) microgel for the encapsulation of methylene blue, an anticancer drug, for its use as breast cancer treatment in MCF-7 cell line. We developed biocompatible microgels based on nonfunctionalized PNIPAM and its corresponding anionically functionalized PNIPAM and polyacrylic acid (PNIPAM-co-PAA) microgel. Methylene blue was used as the photosensitizer drug because of its ability to generate toxic reactive oxygen species upon exposure to light at 664 nm. Core PNIPAM and core/shell PNIPAM-co-PAA microgels were synthesized and characterized using ultraviolet-visible spectroscopy and dynamic light scattering. The effect of methylene blue was evaluated using the MCF-7 cell line. Loading of methylene blue in core PNIPAM microgel was higher than that in the core/shell PNIPAM-co-PAA microgel, indicating that electrostatic interactions did not play an important role in loading a cationic drug. This behavior is probably due to the skin layer inhibiting the high uptake of drugs in the PNIPAM-co-PAA microgel. Core PNIPAM microgel effectively retained the cationic drug (i.e., methylene blue) for several hours compared to core/shell PNIPAM-co-PAA and enhanced its photodynamic efficacy in vitro more than that of free methylene blue. Our results showed that the employment of core PNIPAM and core/shell PNIPAM-co-PAA microgels enhanced the encapsulation of methylene blue. Core PNIPAM microgel released the drug more slowly than did core/shell PNIPAM-co-PAA, and it effectively inhibited the growth of MCF-7 cells.

Vitamin C-driven epirubicin loading into liposomes.

PubMed

Lipka, Dominik; Gubernator, Jerzy; Filipczak, Nina; Barnert, Sabine; Süss, Regine; Legut, Mateusz; Kozubek, Arkadiusz

2013-01-01

The encapsulation of anticancer drugs in a liposome structure protects the drug during circulation and increases drug accumulation in the cancer tissue and antitumor activity while decreasing drug toxicity. This paper presents a new method of active drug loading based on a vitamin C pH/ion gradient. Formulations were characterized in terms of the following parameters: optimal external pH, time and drug-to-lipid ratio for the purpose of remote loading, and in vitro stability. In the case of the selected drug, epirubicin (EPI), its coencapsulation increases its anticancer activity through a possibly synergistic effect previously reported by other groups for a free nonencapsulated drug/vitamin C cocktail. The method also has another advantage over other remote-loading methods: it allows faster drug release through liposome destabilization at the tumor site, thanks to the very good solubility of the EPI vitamin C salt, as seen on cryogenic transmission electron microscopy images. This influences the drug-release process and increases the anticancer activity of the liposome formulation. The liposomes are characterized as stable, with very good pharmacokinetics (half-life 18.6 hours). The antitumor activity toward MCF-7 and 4T-1 breast cancer cells was higher in the case of EPI loaded via our gradient than via an ammonium sulfate gradient. Finally, the EPI liposomal formulation and the free drug were tested using the murine 4T-1 breast cancer model. The antitumor activity of the encapsulated drug was confirmed (tumor-growth inhibition over 40% from day 16 until the end of the experiment), and the free drug was shown to have no anticancer activity at the tested dose.

Biodegradable Chitosan Magnetic Nanoparticle Carriers for Sub-Cellular Targeting Delivery of Artesunate for Efficient Treatment of Breast Cancer

NASA Astrophysics Data System (ADS)

Subramanian, Natesan; Abimanyu, Sugumaran; Vinoth, Jeevanesan; Sekar, Ponnusamy Chandra

2010-12-01

Artesunate is a semi-synthetic derivative of artemisinin, the active principle extracted from Artemisia annua. It possesses good anti-proliferative activity and anti-angiogenic activity with very low toxicity to normal healthy cells. The drawback of most cancer drugs is their inability to accumulate selectively in the cancerous cells. So, large quantities of doses have to be administered to get the required therapeutic concentration in the target site and it resulted in many serious side effects due to the exposure of healthy cells to higher concentrations of cytotoxic drugs. The problem may be solved by selectively and quantitatively accumulating the drug at target site using magnetic nanoparticles guided by an externally applied magnetic field. A modest attempt has been made in this present study, the artesunate magnetic nanoparticle was successfully formulated using two forms of chitosan and evaluated for its in-vitro characteristics like surface morphology, particle size and distribution, zeta potential, magnetic susceptibility, encapsulation efficiency, loading capacity and in-vitro drug release. The synthesized magnetite size was 73 nm and the size of developed magnetic nanoparticles of artesunate was in the range of 90 to 575 nm. Acetic acid soluble chitosan at low concentration exhibit highest encapsulation efficiency and drug loading whereas increase in water soluble chitosan concentration increases the encapsulation efficiency and drug loading in formulations. The developed chitosan magnetic nanoparticles of artesunate shows better release characteristics and may be screened for its in-vivo breast cancer activity.

Drug delivery monitoring by photoacoustic tomography with an ICG encapsulated double emulsion

NASA Astrophysics Data System (ADS)

Wang, Xueding; Rajian, Justin R.; Fabiilli, Mario L.; Fowlkes, J. Brian; Carson, Paul L.

2012-02-01

We successfully encapsulated ICG in an ultrasound-triggerable perfluorocarbon double emulsion that prevents ICG from binding with plasma proteins. Photoacoustic spectral measurements on point target as well as 2-D photoacoustic images of blood vessels revealed that the photoacoustic spectrum changes significantly in blood when the ICG-loaded emulsion undergoes acoustic droplet vaporization (ADV), which is the conversion of liquid droplets into gas bubbles using ultrasound. Other than providing a new photoacoustic contrast agent, the ICG encapsulated double emulsion, when imaged with photoacoustic tomography, could facilitate spatial and quantitative monitoring of ultrasound initiated drug delivery.

Comparative studies on osmosis based encapsulation of sodium diclofenac in porcine and outdated human erythrocyte ghosts.

PubMed

Bukara, Katarina; Drvenica, Ivana; Ilić, Vesna; Stančić, Ana; Mišić, Danijela; Vasić, Borislav; Gajić, Radoš; Vučetić, Dušan; Kiekens, Filip; Bugarski, Branko

2016-12-20

The objective of our study was to develop controlled drug delivery system based on erythrocyte ghosts for amphiphilic compound sodium diclofenac considering the differences between erythrocytes derived from two readily available materials - porcine slaughterhouse and outdated transfusion human blood. Starting erythrocytes, empty erythrocyte ghosts and diclofenac loaded ghosts were compared in terms of the encapsulation efficiency, drug releasing profiles, size distribution, surface charge, conductivity, surface roughness and morphology. The encapsulation of sodium diclofenac was performed by an osmosis based process - gradual hemolysis. During this process sodium diclofenac exerted mild and delayed antihemolytic effect and increased potassium efflux in porcine but not in outdated human erythrocytes. FTIR spectra revealed lack of any membrane lipid disorder and chemical reaction with sodium diclofenac in encapsulated ghosts. Outdated human erythrocyte ghosts with detected nanoscale damages and reduced ability to shrink had encapsulation efficiency of only 8%. On the other hand, porcine erythrocyte ghosts had encapsulation efficiency of 37% and relatively slow drug release rate. More preserved structure and functional properties of porcine erythrocytes related to their superior encapsulation and release performances, define them as more appropriate for the usage in sodium diclofenac encapsulation process. Copyright © 2016 Elsevier B.V. All rights reserved.

Boron nitride nanotube as a delivery system for platinum drugs: Drug encapsulation and diffusion coefficient prediction.

PubMed

Khatti, Zahra; Hashemianzadeh, Seyed Majid

2016-06-10

Molecular dynamics (MD) simulation has been applied to investigate a drug delivery system based on boron nitride nanotubes, particularly the delivery of platinum-based anticancer drugs. For this propose, the behavior of carboplatin drugs inserted in boron nitride nanotubes (BNNT) as a carrier was studied. The diffusion rate of water molecules and carboplatin was investigated inside functionalized and pristine boron nitride nanotubes. The penetration rate of water and drug in functionalized BNNT was higher than that in pristine BNNT due to favorable water-mediated hydrogen bonding in hydroxyl edge-functionalized BNNT. Additionally, the encapsulation of multiple carboplatin drugs inside functionalized boron nitride nanotubes with one to five drug molecules confined inside the nanotube cavity was examined. At high drug loading, the hydrogen bond formation between adjacent drugs and the non-bonded van der Waals interaction between carboplatin and functionalized BNNT inner surface were found to be influential in drug displacement within the functionalized BNNT cavity for higher drug-loading capacity. Copyright © 2016 Elsevier B.V. All rights reserved.

Co-delivery of doxorubicin and arsenite with reduction and pH dual-sensitive vesicle for synergistic cancer therapy

NASA Astrophysics Data System (ADS)

Zhang, Lu; Xiao, Hong; Li, Jingguo; Cheng, Du; Shuai, Xintao

2016-06-01

Drug resistance is the underlying cause for therapeutic failure in clinical cancer chemotherapy. A prodrug copolymer mPEG-PAsp(DIP-co-BZA-co-DOX) (PDBD) was synthesized and assembled into a nanoscale vesicle comprising a PEG corona, a reduction and pH dual-sensitive hydrophobic membrane and an aqueous lumen encapsulating doxorubicin hydrochloride (DOX.HCl) and arsenite (As). The dual stimulation-sensitive design of the vesicle gave rise to rapid release of the physically entrapped DOX.HCl and arsenite inside acidic lysosomes, and chemically conjugated DOX inside the cytosol with high glutathione (GSH) concentration. In the optimized concentration range, arsenite previously recognized as a promising anticancer agent from traditional Chinese medicine can down-regulate the expressions of anti-apoptotic and multidrug resistance proteins to sensitize cancer cells to chemotherapy. Consequently, the DOX-As-co-loaded vesicle demonstrated potent anticancer activity. Compared to the only DOX-loaded vesicle, the DOX-As-co-loaded one induced more than twice the apoptotic ratio of MCF-7/ADR breast cancer cells at a low As concentration (0.5 μM), due to the synergistic effects of DOX and As. The drug loading strategy integrating chemical conjugation and physical encapsulation in stimulation-sensitive carriers enabled efficient drug loading in the formulation.Drug resistance is the underlying cause for therapeutic failure in clinical cancer chemotherapy. A prodrug copolymer mPEG-PAsp(DIP-co-BZA-co-DOX) (PDBD) was synthesized and assembled into a nanoscale vesicle comprising a PEG corona, a reduction and pH dual-sensitive hydrophobic membrane and an aqueous lumen encapsulating doxorubicin hydrochloride (DOX.HCl) and arsenite (As). The dual stimulation-sensitive design of the vesicle gave rise to rapid release of the physically entrapped DOX.HCl and arsenite inside acidic lysosomes, and chemically conjugated DOX inside the cytosol with high glutathione (GSH) concentration. In the optimized concentration range, arsenite previously recognized as a promising anticancer agent from traditional Chinese medicine can down-regulate the expressions of anti-apoptotic and multidrug resistance proteins to sensitize cancer cells to chemotherapy. Consequently, the DOX-As-co-loaded vesicle demonstrated potent anticancer activity. Compared to the only DOX-loaded vesicle, the DOX-As-co-loaded one induced more than twice the apoptotic ratio of MCF-7/ADR breast cancer cells at a low As concentration (0.5 μM), due to the synergistic effects of DOX and As. The drug loading strategy integrating chemical conjugation and physical encapsulation in stimulation-sensitive carriers enabled efficient drug loading in the formulation. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07868g

PLA-PEG-PLA copolymer-based polymersomes as nanocarriers for delivery of hydrophilic and hydrophobic drugs: preparation and evaluation with atorvastatin and lisinopril.

PubMed

Danafar, H; Rostamizadeh, K; Davaran, S; Hamidi, M

2014-10-01

Tri-block poly(lactide)-poly(ethylene glycol)-poly(lactide) (PLA-PEG-PLA) copolymers were synthesized and used to prepare polymersomes loaded separately by the hydrophobic and hydrophilic model drugs, atorvastatin and lisinopril, respectively. The resulting nanostructures were characterized by various techniques such as FTIR, DSC, PCS and AFM. The polymersomes exhibited high encapsulation efficiencies of almost 78% and 70.8% for atorvastatin and lisinopril, respectively. Investigation on FTIR and DSC results revealed that such a high encapsulation efficiency is due to strong interaction between atorvastatin and the copolymer. The impact of drug/copolymer ratio and copolymer composition on drug-loading efficiency and drug release behavior were also studied. The results showed that in case of lisinopril, polymersomes exhibited a triphasic drug release, while for atorvastatin a biphasic release profile was obtained. Overall, the results indicated that PLA-PEG-PLA polymersomes can be considered as a promising carrier for both hydrophilic and hydrophobic drugs.

Targeted Cellular Drug Delivery using Tailored Dendritic Nanostructures

NASA Astrophysics Data System (ADS)

Kannan, Rangaramanujam; Kolhe, Parag; Kannan, Sujatha; Lieh-Lai, Mary

2002-03-01

Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorble, ‘peripheral’ functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug and gene delivery. The large number of end groups can also be tailored to create special affinity to targeted cells, and can also encapsulate drugs and deliver them in a controlled manner. We are developing tailor-modified dendritic systems for drug delivery. Synthesis, in-vitro drug loading, in-vitro drug delivery, and the targeting efficiency to the cell are being studied systematically using a wide variety of experimental tools. Polyamidoamine and Polyol dendrimers, with different generations and end-groups are studied, with drugs such as Ibuprofen and Methotrexate. Our results indicate that a large number of drug molecules can be encapsulated/attached to the dendrimers, depending on the end groups. The drug-encapsulated dendrimer is able to enter the cells rapidly and deliver the drug. Targeting strategies being explored

Preparation, characterization, drug release and computational modelling studies of antibiotics loaded amorphous chitin nanoparticles.

PubMed

Gayathri, N K; Aparna, V; Maya, S; Biswas, Raja; Jayakumar, R; Mohan, C Gopi

2017-12-01

We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were -7.3kcal/mol, -5.1kcal/mol and -8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles

PubMed Central

Pan-In, Porntip; Wanichwecharungruang, Supason; Hanes, Justin; Kim, Anthony J

2014-01-01

Garcinia mangostana Linn extract (GME) is a natural product that has received considerable attention in cancer therapy, and has the potential to reduce side effects of chemotherapeutics and improve efficacy. We formulated GME-encapsulated ethyl cellulose (GME-EC) and a polymer blend of ethyl cellulose and methyl cellulose (GME-EC/MC) nanoparticles. We achieved high drug-loading and encapsulation efficiency using a solvent-displacement method with particle sizes around 250 nm. Cellular uptake and accumulation of GME was higher for GME-encapsulated nanoparticles compared to free GME. In vitro cytotoxicity analysis showed effective anticancer activity of GME-EC and GME-EC/MC nanoparticles in HeLa cells in a dose-dependent manner. GME-EC/MC nanoparticles showed approximately twofold-higher anticancer activity compared to GME-EC nanoparticles, likely due to their enhanced bioavailability. GME-encapsulated nanoparticles primarily entered HeLa cells by clathrin-mediated endocytosis and trafficked through the endolysosomal pathway. As far as we know, this is the first report on the cellular uptake and intracellular trafficking mechanism of drug-loaded cellulose-based nanoparticles. In summary, encapsulation of GME using cellulose-derivative nanoparticles – GME-EC and GME-EC/MC nanoparticles – successfully improved the bioavailability of GME in aqueous solution, enhanced cellular uptake, and displayed effective anticancer activity. PMID:25125977

Nanostructured polysaccharidic microcapsules for intracellular release of cisplatin.

PubMed

Vergaro, Viviana; Papadia, Paride; Petrini, Paola; Fanizzi, Francesco Paolo; De Pascali, Sandra A; Baldassarre, Francesca; Pastorino, Laura; Ciccarella, Giuseppe

2017-06-01

Carbohydrate polimeric microcapsules were assembled using a LbL approach onto a CaCO 3 core. The microcapsules were used to delivery the anticancer drug cisplatin into HeLa and MCF-7 cancer cell lines. Drug encapsulation, measured by ICP spectroscopy, was around 50% of the charging solution. Fluorimetric measurements showed an efficient cellular uptake of polysacchardic microcapsules in both cell lines. The drug-loaded capsules demonstrated a better efficiency against cell viability than the free drug. Specifically, the amount of platinum reaching genomic DNA was measured, showing that encapsulation improves the nuclear delivery of the drug for both cell lines. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistic role of solid lipid and porous silica in improving the oral delivery of weakly basic poorly water soluble drugs.

PubMed

Yasmin, Rokhsana; Rao, Shasha; Bremmell, Kristen; Prestidge, Clive

2017-01-01

Oral absorption of weakly basic drugs (e.g. cinnarizine (CIN)) is limited by their pH dependent precipitation in intestinal conditions. To overcome this challenge, a novel drug delivery system composed of solid lipid and porous silica, namely silica encapsulated solid lipid (SESL) particles, was developed via hot homogenization of melted lipid dispersion, followed by ultra-sonication of the silica stabilized homogenized melted lipid dispersion. Scanning electron microscope (SEM) images of the SESL formulation revealed non-spherical and aggregated hybrid particles, with rough exterior and structured nanoparticles visible on the surface. A 1.5, 2.2 and 7-fold improvement in the dissolution of CIN was observed for the SESL particles, under simulated intestinal non-digesting conditions, in comparison to the drug loaded in solid lipid (CIN-SL) matrix, drug loaded in porous silica (CIN-PS) and pure drug powder. Under simulated intestinal digestive condition, significant improvement in the drug solubilization was reported for the SESL formulation in compared to the individual drug loaded systems i.e. CIN-PS and CIN-SL. Thereby, silica encapsulated solid lipid system provides a promising oral delivery approach for poorly water soluble weakly basic drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Vitamin C-driven epirubicin loading into liposomes

PubMed Central

Lipka, Dominik; Gubernator, Jerzy; Filipczak, Nina; Barnert, Sabine; Süss, Regine; Legut, Mateusz; Kozubek, Arkadiusz

2013-01-01

The encapsulation of anticancer drugs in a liposome structure protects the drug during circulation and increases drug accumulation in the cancer tissue and antitumor activity while decreasing drug toxicity. This paper presents a new method of active drug loading based on a vitamin C pH/ion gradient. Formulations were characterized in terms of the following parameters: optimal external pH, time and drug-to-lipid ratio for the purpose of remote loading, and in vitro stability. In the case of the selected drug, epirubicin (EPI), its coencapsulation increases its anticancer activity through a possibly synergistic effect previously reported by other groups for a free nonencapsulated drug/vitamin C cocktail. The method also has another advantage over other remote-loading methods: it allows faster drug release through liposome destabilization at the tumor site, thanks to the very good solubility of the EPI vitamin C salt, as seen on cryogenic transmission electron microscopy images. This influences the drug-release process and increases the anticancer activity of the liposome formulation. The liposomes are characterized as stable, with very good pharmacokinetics (half-life 18.6 hours). The antitumor activity toward MCF-7 and 4T-1 breast cancer cells was higher in the case of EPI loaded via our gradient than via an ammonium sulfate gradient. Finally, the EPI liposomal formulation and the free drug were tested using the murine 4T-1 breast cancer model. The antitumor activity of the encapsulated drug was confirmed (tumor-growth inhibition over 40% from day 16 until the end of the experiment), and the free drug was shown to have no anticancer activity at the tested dose. PMID:24101870

Fluorescent polymeric micelles with aggregation-induced emission properties for monitoring the encapsulation of doxorubicin.

PubMed

Chen, Jen-Ing; Wu, Wen-Chung

2013-05-01

A new type of fluorescent polymeric micelles is developed by self-assembly from a series of amphiphilic block copolymers, poly(ethylene glycol)-b-poly[styrene-co-(2-(1,2,3,4,5-pentaphenyl-1H-silol-1-yloxy)ethyl methacrylate)] [PEG-b-P(S-co-PPSEMA)]. Their capability of loading doxorubicin (DOX) is investigated by monitoring the loading content, encapsulation efficiency, and photophysical properties of micelles. Förster resonance energy transfer from PPSEMA to DOX is observed in DOX-loaded micelles, which can serve as an indication of successful encapsulation of DOX in these micelles. The application of this new type of fluorescent polymeric micelles as a fluorescent probe and an anticancer drug carrier simultaneously is explored by studying the intracellular uptake of DOX-loaded micelles. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

β-Lapachone and Paclitaxel Combination Micelles with Improved Drug Encapsulation and Therapeutic Synergy as Novel Nanotherapeutics for NQO1-Targeted Cancer Therapy.

PubMed

Zhang, Ling; Chen, Zhen; Yang, Kuan; Liu, Chun; Gao, Jinming; Qian, Feng

2015-11-02

β-Lapachone (LPC) is a novel cytotoxic agent that is bioactivated by NADP(H): quinone oxidoreductase 1 (NQO1), an enzyme elevated in a variety of tumors, such as non-small cell lung cancer (NSCLC), pancreatic cancer, liver cancer, and breast cancer. Despite its unique mechanism of action, its clinical evaluation has been largely hindered by low water solubility, short blood half-life, and narrow therapeutic window. Although encapsulation into poly(ethylene glycol)-b-poly(D,L-lactic acid) (PEG-PLA) micelles could modestly improve its solubility and prolong its half-life, the extremely fast intrinsic crystallization tendency of LPC prevents drug loading higher than ∼2 wt %. The physical stability of the LPC-loaded micelles is also far from satisfactory for further development. In this study, we demonstrate that paclitaxel (PTX), a front-line drug for many cancers, can provide two functions when coencapsulated together with LPC in the PEG-PLA micelles; first, as a strong crystallization inhibitor for LPC, thus to significantly increase the LPC encapsulation efficiency in the micelle from 11.7 ± 2.4% to 100.7 ± 2.2%. The total drug loading efficiency of both PTX and LPC in the combination polymeric micelle reached 100.3 ± 3.0%, and the drug loading density reached 33.2 ± 1.0%. Second, the combination of LPC/PTX demonstrates strong synergistic cytotoxicity effect against the NQO1 overexpressing cancer cells, including A549 NSCLC cells, and several pancreatic cancer cells (combination index <1). In vitro drug release study showed that LPC was released faster than PTX either in phosphate-buffered saline (PH = 7.4) or in 1 M sodium salicylate, which agrees with the desired dosing sequence of the two drugs to exert synergistic pharmacologic effect at different cell checkpoints. The PEG-PLA micelles coloaded with LPC and PTX offer a novel nanotherapeutic, with high drug loading, sufficient physical stability, and biological synergy to increase drug delivery efficiency and optimize the therapeutic window for NOQ1-targeted therapy of cancer.

Hydrophobic lapatinib encapsulated dextran-chitosan nanoparticles using a toxic solvent free method: fabrication, release property & in vitro anti-cancer activity.

PubMed

Mobasseri, Rezvan; Karimi, Mahdi; Tian, Lingling; Naderi-Manesh, Hossein; Ramakrishna, Seeram

2017-05-01

Dextran sulfate-chitosan (DS-CS) nanoparticles, which possesses properties such as nontoxicity, biocompatibility and biodegradability have been employed as drug carriers in cancer therapy. In this study, DS-CS nanoparticles were synthesized and their sizes were controlled by a modification of the divalent cations cross-linkers (Ca 2+ , Zn 2+ or Mg 2+ ). Based on the optimized processing parameters, lapatinib encapsulated nanoparticles were developed and characterized by Dynamics Light Scattering (DLS) measurements, Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM). Calcium chloride (CaCl 2 ) facilitated the formation of bare (100.3±0.80nm) and drug-loaded nanoparticles (134.3±1.3nm) with narrow size distributions being the best cross-linker. The surface potential of drug-loaded nanoparticles was -16.8±0.47mV and its entrapment and loading efficiency were 76.74±1.73% and 47.36±1.27%, respectively. Cellular internalization of nanoparticles was observed by fluorescence microscopy and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay was used to determine cytotoxicity of bare and drug-loaded nanoparticles in comparison to the free drug lapatinib. The MTT assay showed that drug-loaded nanoparticles had comparable anticancer activity to free drug within a duration of 48h. The aforementioned results showed that the DS-CS nanoparticles were able to entrap, protect and release the hydrophobic drug, lapatinib in a controlled pattern and could further serve as a suitable drug carrier for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

PubMed Central

Halayqa, Mohammed; Domańska, Urszula

2014-01-01

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles. PMID:25535080

PLGA biodegradable nanoparticles containing perphenazine or chlorpromazine hydrochloride: effect of formulation and release.

PubMed

Halayqa, Mohammed; Domańska, Urszula

2014-12-22

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

Formulation and in vitro characterization of protein-loaded liposomes

NASA Astrophysics Data System (ADS)

Kuzimski, Lauren

Background/Objective: Protein-based drugs are increasingly used to treat a variety of conditions including cancer and cardio-vascular disease. Due to the immune system's innate ability to degrade the foreign particles quickly, protein-based treatments are generally short-lived. To address this limitation, the objective of the study was to: 1) develop protein-loaded liposomes; 2) characterize size, stability, encapsulation efficiency and rate of protein release; and 3) determine intracellular uptake and distribution; and 4) protein structural changes. Method: Liposomes were loaded with a fluorescent-albumin using freeze-thaw (F/T) methodology. Albumin encapsulation and release were quantified by fluorescence spectroscopic techniques. Flow cytometry was used to determine liposome uptake by macrophages. Epifluorescence microscopy was used to determine cellular distribution of liposomes. Stability was determined using dynamic light scattering by measuring liposome size over one month period. Protein structure was determined using circular dichroism (CD). Result: Encapsulation of albumin in liposome was ˜90% and was dependent on F/T rates, with fifteen cycles yielding the highest encapsulation efficacy (p < 0.05). Albumin-loaded liposomes demonstrated consistent size (<300nm). Release of encapsulated albumin in physiological buffer at 25°C was ˜60% in 72 h. Fluorescence imaging suggested an endosomal route of cellular entry for the FITC-albumin liposome with maximum uptake rates in immune cells (30% at 2hour incubation). CD suggested protein structure is minimally impacted by freeze-thaw methodology. Conclusion: Using F/T as a loading method, we were able to successfully achieve a protein-loaded liposome that was under 300nm, had encapsulation of ˜90%. Synthesized liposomes demonstrated a burst release of encapsulate protein (60%) at 72 hours. Cellular trafficking confirmed endosomal uptake, and minimal protein damage was noticed in CD.

Hydrophobic ion pairing of a minocycline/Ca(2+)/AOT complex for preparation of drug-loaded PLGA nanoparticles with improved sustained release.

PubMed

Holmkvist, Alexander Dontsios; Friberg, Annika; Nilsson, Ulf J; Schouenborg, Jens

2016-02-29

Polymeric nanoparticles is an established and efficient means to achieve controlled release of drugs. Incorporation of minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, into biodegradable nanoparticles may therefore provide an efficient means to combat foreign body reactions to implanted electrodes in the brain. However, minocycline is commonly associated with poor encapsulation efficiencies and/or fast release rates due to its high solubility in water. Moreover, minocycline is unstable under conditions of low and high pH, heat and exposure to light, which exacerbate the challenges of encapsulation. In this work drug loaded PLGA nanoparticles were prepared by a modified emulsification-solvent-diffusion technique and characterized for size, drug encapsulation and in vitro drug release. A novel hydrophobic ion pair complex of minocycline, Ca(2+) ions and the anionic surfactant AOT was developed to protect minocycline from degradation and prolong its release. The optimized formulation resulted in particle sizes around 220 nm with an entrapment efficiency of 43% and showed drug release over 30 days in artificial cerebrospinal fluid. The present results constitute a substantial increase in release time compared to what has hitherto been achieved for minocycline and indicate that such particles might provide useful for sustained drug delivery in the CNS. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Layer-by-layer polyelectrolyte-polyester hybrid microcapsules for encapsulation and delivery of hydrophobic drugs.

PubMed

Luo, Rongcong; Venkatraman, Subbu S; Neu, Björn

2013-07-08

A two-step process is developed to form layer-by-layer (LbL) polyelectrolyte microcapsules, which are able to encapsulate and deliver hydrophobic drugs. Spherical porous calcium carbonate (CaCO3) microparticles were used as templates and coated with a poly(lactic acid-co-glycolic acid) (PLGA) layer containing hydrophobic compounds via an in situ precipitation gelling process. PLGA layers that precipitated from N-methyl-2-pyrrolidone (NMP) had a lower loading and smoother surface than those precipitated from acetone. The difference may be due to different viscosities and solvent exchange dynamics. In the second step, the successful coating of multilayer polyelectrolytes poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) onto the PLGA coated CaCO3 microparticles was confirmed with AFM and ζ-potential studies. The release of a model hydrophobic drug, ibuprofen, from these hybrid microcapsules with different numbers of PAH/PSS layers was investigated. It was found that the release of ibuprofen decreases with increasing layer numbers demonstrating the possibility to control the release of ibuprofen with these novel hybrid microcapsules. Besides loading of hydrophobic drugs, the interior of these microcapsules can also be loaded with hydrophilic compounds and functional nanoparticles as demonstrated by loading with Fe3O4 nanoparticles, forming magnetically responsive dual drug releasing carriers.

Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles

NASA Astrophysics Data System (ADS)

Dian, Linghui; Yu, Enjiang; Chen, Xiaona; Wen, Xinguo; Zhang, Zhengzan; Qin, Lingzhen; Wang, Qingqing; Li, Ge; Wu, Chuanbin

2014-12-01

To improve its poor aqueous solubility and stability, the potential chemotherapeutic drug quercetin was encapsulated in soluplus polymeric micelles by a modified film dispersion method. With the encapsulation efficiency over 90%, the quercetin-loaded polymeric micelles (Qu-PMs) with drug loading of 6.7% had a narrow size distribution around mean size of 79.00 ± 2.24 nm, suggesting the complete dispersibility of quercetin in water. X-ray diffraction (XRD) patterns illustrated that quercetin was in amorphous or molecular form within PMs. Fourier transform infrared spectroscopy (FTIR) indicated that quercetin formed intermolecular hydrogen bonding with carriers. An in vitro dialysis test showed the Qu-PMs possessed significant sustained-release property, and the formulation was stable for at least 6 months under accelerated conditions. The pharmacokinetic study in beagle dogs showed that absorption of quercetin after oral administration of Qu-PMs was improved significantly, with a half-life 2.19-fold longer and a relative oral bioavailability of 286% as compared to free quercetin. Therefore, these novel soluplus polymeric micelles can be applied to encapsulate various poorly water-soluble drugs towards a development of more applicable therapeutic formulations.

Multifunctional biodegradable polymer nanoparticles with uniform sizes: generation and in vitro anti-melanoma activity

NASA Astrophysics Data System (ADS)

Liang, Ruijing; Wang, Jing; Wu, Xian; Dong, Liyun; Deng, Renhua; Wang, Ke; Sullivan, Martin; Liu, Shanqin; Wu, Min; Tao, Juan; Yang, Xiangliang; Zhu, Jintao

2013-11-01

We present a simple, yet versatile strategy for the fabrication of uniform biodegradable polymer nanoparticles (NPs) with controllable sizes by a hand-driven membrane-extrusion emulsification approach. The size and size distribution of the NPs can be easily tuned by varying the experimental parameters, including initial polymer concentration, surfactant concentration, number of extrusion passes, membrane pore size, and polymer molecular weight. Moreover, hydrophobic drugs (e.g., paclitaxel (PTX)) and inorganic NPs (e.g., quantum dots (QDs) and magnetic NPs (MNPs)) can be effectively and simultaneously encapsulated into the polymer NPs to form the multifunctional hybrid NPs through this facile route. These PTX-loaded NPs exhibit high encapsulation efficiency and drug loading density as well as excellent drug sustained release performance. As a proof of concept, the A875 cell (melanoma cell line) experiment in vitro, including cellular uptake analysis by fluorescence microscope, cytotoxicity analysis of NPs, and magnetic resonance imaging (MRI) studies, indicates that the PTX-loaded hybrid NPs produced by this technique could be potentially applied as a multifunctional delivery system for drug delivery, bio-imaging, and tumor therapy, including malignant melanoma therapy.

Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles prepared by double emulsion technique for controlled delivery

PubMed Central

Giri, Tapan Kumar; Choudhary, Chhatrapal; Ajazuddin; Alexander, Amit; Badwaik, Hemant; Tripathi, Dulal Krishna

2012-01-01

Several methods and techniques are potentially useful for the preparation of microparticles in the field of controlled drug delivery. The type and the size of the microparticles, the entrapment, release characteristics and stability of drug in microparticles in the formulations are dependent on the method used. One of the most common methods of preparing microparticles is the single emulsion technique. Poorly soluble, lipophilic drugs are successfully retained within the microparticles prepared by this method. However, the encapsulation of highly water soluble compounds including protein and peptides presents formidable challenges to the researchers. The successful encapsulation of such compounds requires high drug loading in the microparticles, prevention of protein and peptide degradation by the encapsulation method involved and predictable release, both rate and extent, of the drug compound from the microparticles. The above mentioned problems can be overcome by using the double emulsion technique, alternatively called as multiple emulsion technique. Aiming to achieve this various techniques have been examined to prepare stable formulations utilizing w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews the current state of the art in double emulsion based technologies for the preparation of microparticles including the investigation of various classes of substances that are pharmaceutically and biopharmaceutically active. PMID:23960828

Fabrication of a multifunctional nano-in-micro drug delivery platform by microfluidic templated encapsulation of porous silicon in polymer matrix.

PubMed

Zhang, Hongbo; Liu, Dongfei; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Herranz-Blanco, Bárbara; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2014-07-09

A multifunctional nano-in-micro drug delivery platform is developed by conjugating the porous silicon nanoparticles with mucoadhesive polymers and subsequent encapsulation into a pH-responsive polymer using microfluidics. The multistage platform shows monodisperse size distribution and pH-responsive payload release, and the released nanoparticles are mucoadhesive. Moreover, this platform is capable of simultaneously loading and releasing multidrugs with distinct properties. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Drug-loaded erythrocytes: on the road toward marketing approval

PubMed Central

Bourgeaux, Vanessa; Lanao, José M; Bax, Bridget E; Godfrin, Yann

2016-01-01

Erythrocyte drug encapsulation is one of the most promising therapeutic alternative approaches for the administration of toxic or rapidly cleared drugs. Drug-loaded erythrocytes can operate through one of the three main mechanisms of action: extension of circulation half-life (bioreactor), slow drug release, or specific organ targeting. Although the clinical development of erythrocyte carriers is confronted with regulatory and development process challenges, industrial development is expanding. The manufacture of this type of product can be either centralized or bedside based, and different procedures are employed for the encapsulation of therapeutic agents. The major challenges for successful industrialization include production scalability, process validation, and quality control of the released therapeutic agents. Advantages and drawbacks of the different manufacturing processes as well as success key points of clinical development are discussed. Several entrapment technologies based on osmotic methods have been industrialized. Companies have already achieved many of the critical clinical stages, thus providing the opportunity in the future to cover a wide range of diseases for which effective therapies are not currently available. PMID:26929599

Drug-loaded erythrocytes: on the road toward marketing approval.

PubMed

Bourgeaux, Vanessa; Lanao, José M; Bax, Bridget E; Godfrin, Yann

2016-01-01

Erythrocyte drug encapsulation is one of the most promising therapeutic alternative approaches for the administration of toxic or rapidly cleared drugs. Drug-loaded erythrocytes can operate through one of the three main mechanisms of action: extension of circulation half-life (bioreactor), slow drug release, or specific organ targeting. Although the clinical development of erythrocyte carriers is confronted with regulatory and development process challenges, industrial development is expanding. The manufacture of this type of product can be either centralized or bedside based, and different procedures are employed for the encapsulation of therapeutic agents. The major challenges for successful industrialization include production scalability, process validation, and quality control of the released therapeutic agents. Advantages and drawbacks of the different manufacturing processes as well as success key points of clinical development are discussed. Several entrapment technologies based on osmotic methods have been industrialized. Companies have already achieved many of the critical clinical stages, thus providing the opportunity in the future to cover a wide range of diseases for which effective therapies are not currently available.

Development of pH Sensitive Nanoparticles for Intestinal Drug Delivery Using Chemically Modified Guar Gum Co-Polymer.

PubMed

Varma, Vegesna Naga Sravan Kumar; Shivakumar, Hosakote Gurumalappa; Balamuralidhara, Veerna; Navya, Manne; Hani, Umme

2016-01-01

The aim of the research work was to chemically modify guargum (GG) as a pH sensitive co-polymer and formulating intestinal targeting ESO nanoparticles (NPs) using the synthesized co-polymer. Poly acrylamide-grafted-guar gum (PAAm-g-GG) co-polymer was synthesized by free radical polymerization. Chemical modification of PAAm-g-GG by alkaline hydrolysis results in formation of a pH-sensitive co-polymer. The effect of GG and acryl amide (AAm) on grafting was studied. Esomeprazole magnesium (ESO) loaded pH sensitive NPs were prepared by nano-emulsification polymer crosslinking method and characterized. Sixteen formulations were prepared and the concentration of process variables wasvaried to obtain nanoparticles of 200-600 nm. The NPs were found to be homogenous in size distribution. The encapsulation efficiency and drug loading ranged from 33.2% to 50.1% and 12.2% to 17.2% respectively. Particle size, encapsulation efficiency and drug loading increasedalong with co-polymer concentration. In-vitro release studies at pH 1.2 for 2 h, followed by pH 6.8 showed that environment pH significantly affected the drug release. SEM has shown that NPsare spherical with smooth surface. The pH sensitive PAAm-g-GGNPs resisted the initial release of the drug from the drug loaded NPs in acidic pH and delayed the release process to a longer period in alkaline environment.

Development of pH Sensitive Nanoparticles for Intestinal Drug Delivery Using Chemically Modified Guar Gum Co-Polymer

PubMed Central

Varma, Vegesna Naga Sravan Kumar; Shivakumar, Hosakote Gurumalappa; Balamuralidhara, Veerna; Navya, Manne; Hani, Umme

2016-01-01

The aim of the research work was to chemically modify guargum (GG) as a pH sensitive co-polymer and formulating intestinal targeting ESO nanoparticles (NPs) using the synthesized co-polymer. Poly acrylamide-grafted-guar gum (PAAm-g-GG) co-polymer was synthesized by free radical polymerization. Chemical modification of PAAm-g-GG by alkaline hydrolysis results in formation of a pH-sensitive co-polymer. The effect of GG and acryl amide (AAm) on grafting was studied. Esomeprazole magnesium (ESO) loaded pH sensitive NPs were prepared by nano-emulsification polymer crosslinking method and characterized. Sixteen formulations were prepared and the concentration of process variables wasvaried to obtain nanoparticles of 200-600 nm. The NPs were found to be homogenous in size distribution. The encapsulation efficiency and drug loading ranged from 33.2% to 50.1% and 12.2% to 17.2% respectively. Particle size, encapsulation efficiency and drug loading increasedalong with co-polymer concentration. In-vitro release studies at pH 1.2 for 2 h, followed by pH 6.8 showed that environment pH significantly affected the drug release. SEM has shown that NPsare spherical with smooth surface. The pH sensitive PAAm-g-GGNPs resisted the initial release of the drug from the drug loaded NPs in acidic pH and delayed the release process to a longer period in alkaline environment. PMID:27610149

Dendrimer-based nanocarriers demonstrating a high efficiency for loading and releasing anticancer drugs against cancer cells in vitro and in vivo

NASA Astrophysics Data System (ADS)

Quyen Tran, Ngoc; Khoa Nguyen, Cuu; Phuong Nguyen, Thi

2013-12-01

Dendrimer, a new class of hyper-branched polymer with predetermined molecular weight and well-controlled size, has received much attention in nanobiomedical applications such as drug carrier, gene therapy, disease diagnosis, etc. In this study, pegylated polyamidoamine (PAMAM) dendrimer at generation 3.0 (G 3.0) and carboxylated PAMAM dendrimer G 2.5 were prepared for loading anticancer drugs. For loading cisplatin, carboxylated dendrimer could carry 26.64 wt/wt% of cisplatin. The nanocomplexes have size ranging from 10 to 30 nm in diameter. The drug nanocarrier showed activity against NCI-H460 lung cancer cell line with half maximal inhibitory (IC50) of 23.11 ± 2.08 μg ml-1. Pegylated PAMAM dendrimers (G 3.0) were synthesized below 40 nm in diameter for carrying 5-fluorouracil (5-FU). For 5-FU encapsulation, pegylated dendrimer showed a high drug-loading efficiency of the drug and a slow release profile of 5-FU. The drug nanocarrier system exhibited an antiproliferative activity against MCF-7 cells (breast cancer cell) with a half maximal inhibitory (IC50) of 9.92 ± 0.19 μg ml-1. In vivo tumor xenograft study showed that the 5-FU encapsulated pegylation of dendrimer exhibited a significant decrement in volume of tumor which was generated by MCF-7 cancer cells. These positive results from our studies could pave the ways for further research of drugs dendrimer nanocarriers toward cancer chemotherapy.

L-Asparaginase encapsulated intact erythrocytes for treatment of acute lymphoblastic leukemia (ALL).

PubMed

Kwon, Young Min; Chung, Hee Sun; Moon, Cheol; Yockman, James; Park, Yoon Jeong; Gitlin, Scott D; David, Allan E; Yang, Victor C

2009-11-03

As a primary drug for the treatment of acute lymphoblastic leukemia (ALL), encapsulation of L-asparaginase (ASNase) into red blood cells (RBC) has been popular to circumvent immunogenicity from the exogenous protein. Unlike existing methods that perturbs RBC membranes, we introduce a novel method of RBC-incorporation of proteins using the membrane-translocating low molecular weight protamine (LMWP). Confocal study of fluorescence-labeled LMWP-ovalbumin, as a model protein conjugate, has shown significant fluorescence inside RBCs. Surface morphology by scanning electron microscopy of the RBCs loaded with LMWP-ASNase was indistinguishable with normal RBCs. These drug loaded RBCs also closely resembled the profile of the native erythrocytes in terms of osmotic fragility, oxygen dissociation and hematological parameters. The in vivo half-life of enzyme activity after administering 8 units of RBC/LMWP-ASNase in DBA/2 mice was prolonged to 4.5+/-0.5 days whereas that of RBCs loaded with ASNase via a hypotonic method was 2.4+/-0.7 days. Furthermore, the mean survival time of DBA/2 mice bearing mouse lymphoma cell L5178Y was improved by approximately 44% compared to the saline control group after treatment with the RBC loaded enzymes. From these data, an innovative, novel method for encapsulating proteins into intact and fully functional erythrocytes was established for potential treatment of ALL.

[Preparation and in vitro release characteristics of vincristine sulphate loaded poly (butylcyanoacrylate) nanoparticles].

PubMed

Tan, Rong; Liu, Ying; Feng, Nianping; Zhao, Jihui

2011-06-01

To prepare vincristine sulphate loaded poly (butylcyanoacrylate) nanoparticles (VCR-PBCA-NPs) and to investigate the in vitro release charactersitics. VCR-PBCA-NPs were prepared by emulsion polymerization method, and characterized for morphology, particle size, drug encapsulation efficiency and loading efficiency. The formulation was optimized using central composite design and response surface methodology. In vitro release study of VCR-PBCA-NPs was performed by dialysis technique. Model fitting was used to determine the kinetics and to discuss the mechanism. The nanoparticles were spherical and uniform with a mean diameter of (98.9 +/- 3.05) nm. The drug encapsulation efficiency and loading efficiency were (55.23 +/- 0.96)% and (7.87 +/- 0.11)%, respectively. In vitro release results showed that 63.66% of VCR was released from VCR-PBCA-NPs in 4 h, and the Weibull model fitted VCR release pattern best. The VCR-PBCA-NPs prepared in this study showed sustained release compared with VCR solution.

Nano spray drying for encapsulation of pharmaceuticals.

PubMed

Arpagaus, Cordin; Collenberg, Andreas; Rütti, David; Assadpour, Elham; Jafari, Seid Mahdi

2018-05-17

Many pharmaceuticals such as pills, capsules, or tablets are prepared in a dried and powdered form. In this field, spray drying plays a critical role to convert liquid pharmaceutical formulations into powders. In addition, in many cases it is necessary to encapsulate bioactive drugs into wall materials to protect them against harsh process and environmental conditions, as well as to deliver the drug to the right place and at the correct time within the body. Thus, spray drying is a common process used for encapsulation of pharmaceuticals. In view of the rapid progress of nanoencapsulation techniques in pharmaceutics, nano spray drying is used to improve drug formulation and delivery. The nano spray dryer developed in the recent years provides ultrafine powders at nanoscale and high product yields. In this paper, after explaining the concept of nano spray drying and understanding the key elements of the equipment, the influence of the process parameters on the final powders properties, like particle size, morphology, encapsulation efficiency, drug loading and release, will be discussed. Then, numerous application examples are reviewed for nano spray drying and encapsulation of various drugs in the early stages of product development along with a brief overview of the obtained results and characterization techniques. Copyright © 2018 Elsevier B.V. All rights reserved.

Dextran vesicular carriers for dual encapsulation of hydrophilic and hydrophobic molecules and delivery into cells.

PubMed

Pramod, P S; Takamura, Kathryn; Chaphekar, Sonali; Balasubramanian, Nagaraj; Jayakannan, M

2012-11-12

Dextran vesicular nanoscaffolds were developed based on polysaccharide and renewable resource alkyl tail for dual encapsulation of hydrophilic and hydrophobic molecules (or drugs) and delivery into cells. The roles of the hydrophobic segments on the molecular self-organization of dextran backbone into vesicles or nanoparticles were investigated in detail. Dextran vesicles were found to be a unique dual carrier in which water-soluble molecules (like Rhodamine-B, Rh-B) and polyaromatic anticancer drug (camptothecin, CPT) were selectively encapsulated in the hydrophilic core and hydrophobic layer, respectively. The dextran vesicles were capable of protecting the plasma-sensitive CPT lactone pharmacophore against the hydrolysis by 10× better than the CPT alone in PBS. The aliphatic ester linkage connecting the hydrophobic tail with dextran was found to be cleaved by esterase under physiological conditions for fast releasing of CPT or Rh-B. Cytotoxicity of the dextran vesicle and its drug conjugate were tested on mouse embryonic fibroblast cells (MEFs) using MTT assay. The dextran vesicular scaffold was found to be nontoxic to living cells. CPT loaded vesicles were found to be 2.5-fold more effective in killing fibroblasts compared to that of CPT alone in PBS. Confocal microscopic images confirmed that both Rh-B and CPT loaded vesicles to be taken up by fibroblasts compared to CPT alone, showing a distinctly perinuclear localization in cells. The custom designed dextran vesicular provides new research opportunities for dual loading and delivering of hydrophilic and hydrophobic drug molecules.

Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs?

PubMed

Das, Surajit; Ng, Wai Kiong; Tan, Reginald B H

2012-08-30

In recent years, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are among the popular research topics for the delivery of lipophilic drugs. Although SLNs have demonstrated several beneficial properties as drug-carrier, limited drug-loading and expulsion of drug during storage led to the development of NLCs. However, the superiority of NLCs over SLNs has not been fully established yet due to the contradictory results. In this study, SLNs and NLCs were developed using clotrimazole as model drug. Size, polydispersity index (PI), zeta potential (ZP), drug-loading (L), drug encapsulation efficiency (EE), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), drug release and stability of SLNs and NLCs were compared. Critical process parameters exhibited significant impact on the nanoparticles' properties. Size, PI, ZP and EE of the developed SLNs and NLCs were<100 nm, <0.17, <-22 mV and>82%, respectively. SEM images of SLNs and NLCs revealed spherical shaped particles (≈ 100 nm). DSC and XRD studies indicated slight difference between SLNs and NLCs as well as disappearance of the crystalline peak(s) of the encapsulated drug. NLCs demonstrated faster drug release than SLNs at low drug-loading, whereas there was no significant difference in drug release from SLNs and NLCs at high drug-loading. However, sustained/prolonged drug release was observed from both formulations. Furthermore, this study suggests that the drug release experiment should be designed considering the final application (topical/oral/parenteral) of the product. Regarding stability, NLCs showed better stability (in terms of size, PI, EE and L) than SLNs at 25°C. Moreover, there was no significant difference in drug release profile of NLCs after 3 months storage in compare to fresh NLCs, while significant change in drug release rate was observed in case of SLNs. Therefore, NLCs have an edge over SLNs. Copyright © 2012 Elsevier B.V. All rights reserved.

Doxycycline delivery from PLGA microspheres prepared by a modified solvent removal method.

PubMed

Patel, Roshni S; Cho, Daniel Y; Tian, Cheng; Chang, Amy; Estrellas, Kenneth M; Lavin, Danya; Furtado, Stacia; Mathiowitz, Edith

2012-01-01

We report on the development of a modified solvent removal method for the encapsulation of hydrophilic drugs within poly(lactic-co-glycolic acid) (PLGA). Using a water/oil/oil double emulsion, hydrophilic doxycycline was encapsulated within PLGA spheres with particle diameters ranging from approximately 600 nm to 19 µm. Encapsulation efficiencies of up to 74% were achieved for theoretical loadings from 1% to 10% (w/w), with biphasic release over 85 days with nearly complete release at the end of this time course. About 1% salt was added to the formulations to examine its effects on doxycycline release; salt modulated release only by increasing the magnitude of initial release without altering kinetics. Fourier transform infrared spectroscopy indicated no characteristic differences between doxycycline-loaded and control spheres. Differential scanning calorimetry and X-ray diffraction suggest that there may be a molecular dispersion of the doxycycline within the spheres and the doxycycline may be in an amorphous state, which could explain the slow, prolonged release of the drug.

Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

PubMed Central

Zhang, Yumin; Zhou, Junhui; Yang, Cuihong; Wang, Weiwei; Chu, Liping; Huang, Fan; Liu, Qiang; Deng, Liandong; Kong, Deling; Liu, Jianfeng; Liu, Jinjian

2016-01-01

Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. PMID:27051287

Controlling release from 3D printed medical devices using CLIP and drug-loaded liquid resins.

PubMed

Bloomquist, Cameron J; Mecham, Michael B; Paradzinsky, Mark D; Janusziewicz, Rima; Warner, Samuel B; Luft, J Christopher; Mecham, Sue J; Wang, Andrew Z; DeSimone, Joseph M

2018-05-28

Mass customization along with the ability to generate designs using medical imaging data makes 3D printing an attractive method for the fabrication of patient-tailored drug and medical devices. Herein we describe the application of Continuous Liquid Interface Production (CLIP) as a method to fabricate biocompatible and drug-loaded devices with controlled release properties, using liquid resins containing active pharmaceutical ingredients (API). In this work, we characterize how the release kinetics of a model small molecule, rhodamine B-base (RhB), are affected by device geometry, network crosslink density, and the polymer composition of polycaprolactone- and poly (ethylene glycol)-based networks. To demonstrate the applicability of using API-loaded liquid resins with CLIP, the UV stability was evaluated for a panel of clinically-relevant small molecule drugs. Finally, select formulations were tested for biocompatibility, degradation and encapsulation of docetaxel (DTXL) and dexamethasone-acetate (DexAc). Formulations were shown to be biocompatible over the course of 175 days of in vitro degradation and the clinically-relevant drugs could be encapsulated and released in a controlled fashion. This study reveals the potential of the CLIP manufacturing platform to serve as a method for the fabrication of patient-specific medical and drug-delivery devices for personalized medicine. Copyright © 2018. Published by Elsevier B.V.

Spray-dried nanofibrillar cellulose microparticles for sustained drug release.

PubMed

Kolakovic, Ruzica; Laaksonen, Timo; Peltonen, Leena; Laukkanen, Antti; Hirvonen, Jouni

2012-07-01

Nanofibrillar cellulose (also referred to as cellulose nanofibers, nanocellulose, microfibrillated or nanofibrillated cellulose) has gained a lot of attention in recent years in different research areas including biomedical applications. In this study we have evaluated the applicability of nanofibrillar cellulose (NFC) as a material for the formation of matrix systems for sustained drug delivery. For that purpose, drug loaded NFC microparticles were produced by a spray drying method. The microparticles were characterized in terms of size and morphology, total drug loading, and physical state of the encapsulated drug. Drug release from the microparticles was assessed by dissolution tests, and suitable mathematical models were used to explain the drug releasing kinetics. The particles had spherical shapes with diameters of around 5 μm; the encapsulated drug was mainly in amorphous form. The controlled drug release was achieved. The drug releasing curves were fitted to a mathematical model describing the drug releasing kinetics from a spherical matrix. Different drugs had different release kinetics, which was a consequence of several factors, including different solubilities of the drugs in the chosen medium and different affinities of the drugs to the NFC. It can be concluded that NFC microparticles can sustain drug release by forming a tight fiber network and thus limit drug diffusion from the system. Copyright © 2012 Elsevier B.V. All rights reserved.

Enhanced in Vitro Anti-Tumor Activity of 5-Azacytidine by Entrapment into Solid Lipid Nanoparticles

PubMed Central

Jahanfar, Farhad; Hasani, Akbar; Shanebandi, Dariush; Rahmati, Mohammad; Hamishehkar, Hamed

2016-01-01

Purpose: In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitro effect of encapsulated 5-azacytidine studied on MCF-7 cell lines Methods: 5-azacytidine -loaded solid lipid nanoparticles were produced by double emulsification (w/o/w) method by using stearic acid as lipid matrix, soy lecithin and poloxamer 407 as surfactant and co-surfactant respectively. Particle size, zeta potential, surface morphology, entrapment efficiency and kinetic of drug release were studied. In vitro effect of 5-azacytidine on MCF-7 cell line studied by MTT assay, DAPI staining, Rhodamine B relative uptake, and also Real time RT-PCR was performed for studying difference effect of free and encapsulated drug on expression of RARß2 gene. Results: The formulation F5 with 55.84±0.46 % of entrapment efficiency shows zero order kinetic of drug release and selected for in vitro studies; the cytotoxicity of free drug and encapsulated drug in 48 h of incubation have significant difference. DAPI staining shows morphology of apoptotic nucleus in both free and encapsulated drug, Rhodamine B labeled SLNs show time dependency and accumulation of SLNs in cytoplasm. Real time qRT-PCR doesn’t show any significant difference (p>0.05) in expression of RARß2 gene in both cells treated with free or encapsulated drug. Conclusion: The results of the present study indicated that the entrapment of 5-azacytidine into SLNs enhanced its cytotoxicity performance and may pave a way for the future design of a desired dosage form for 5-azacytidine. PMID:27766220

Depot formulation of vasoactive intestinal peptide by protamine-based biodegradable nanoparticles.

PubMed

Wernig, Karin; Griesbacher, Martin; Andreae, Fritz; Hajos, Franz; Wagner, Julian; Mosgoeller, Wilhelm; Zimmer, Andreas

2008-09-10

Drug delivery of protein and peptide-based drugs, which represent a growing and important therapeutic class, is hampered by these drugs' very short half-lives. High susceptibility towards enzymatic degradation necessitates frequent drug administration followed by poor adherence to therapy. Among these drugs is vasoactive intestinal peptide (VIP), a potent systemic and pulmonary vasodilator, which is a promising drug for the treatment of idiopathic pulmonary arterial hypertension (IPAH). Encapsulation of VIP into the nanoparticle matrix of biodegradable protamine-oligonucleotide nanoparticles (proticles) protects the peptide against rapid enzymatic degradation. Additionally, the nanoparticle matrix will be able to sustain drug release. Proticles consist of 18mer non-sense oligonucleotides and protamine, a polycationic arginine-rich peptide. VIP encapsulation occurs during self-assembly of the components. Within the present study, we evaluate nanoparticle size (hydrodynamic diameter) and zeta potential of VIP-loaded proticles as well as encapsulation efficiency and VIP release. Further, the pharmacological VIP response of "encapsulated VIP" is investigated using an ex vivo lung arterial model system. We found satisfying encapsulation efficiency (up to 80%), VIP release (77-87%), and an appropriate nanoparticle size (177-251 nm). Investigations on rat pulmonary arteries showed a modified VIP response of proticle-associated VIP. We noted differences in the profile of artery relaxation where VIP proticles lead to a 20-30% lower relaxation maximum than aqueous VIP solutions followed by prolonged vasodilatation. Our data indicate that proticles could be a feasible drug delivery system for a pulmonary VIP depot formulation.

Methotrexate loaded alginate microparticles and effect of Ca2+ post-crosslinking: An in vitro physicochemical and biological evaluation.

PubMed

Dhanka, Mukesh; Shetty, Chaitra; Srivastava, Rohit

2018-04-15

Methotrexate (MTX) loaded alginate microparticles were produced by simple water-in-oil (W/O) emulsion solvent diffusion method with homogenization and then subsequently cross-linked by Ca 2+ . The mean sizes of developed microparticles (bare non-crosslinked, crosslinked, drug-loaded non-crosslinked, and drug-loaded cross-linked) were found to be <11μm. The morphology of bare non-crosslinked and crosslinked microparticles were observed to be spherical with smooth surface morphology. However, MTX loaded non-crosslinked and crosslinked microparticles were found to have an irregular shape with rough surface morphology. The encapsulation efficiency (% EE) and loading capacity (% LC) of MTX loaded non-crosslinked microparticles were estimated to be 92.19±1.85 and 9.35±0.22, respectively. However, in case of cross-linked microparticles, the % EE and % LC values slightly decreased, i.e., 83.26±1.69% and 8.44±0.21%, respectively. Crosslinked microparticles were found to release MTX at a slower rate as compared to non-crosslinked microparticles. The physicochemical characterizations of microparticles by Fourier Transform Infrared Spectroscopy and High-Resolution X-Ray Diffraction have shown that drug encapsulated in the microparticles without chemical interactions has lost its crystalline nature. The biocompatibility and hemocompatibility studies of the microparticles have demonstrated that microparticles are biocompatible and were non-hemolytic at low concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

Paclitaxel loaded folic acid targeted nanoparticles of mixed lipid-shell and polymer-core: in vitro and in vivo evaluation.

PubMed

Zhao, Peiqi; Wang, Hanjie; Yu, Man; Liao, Zhenyu; Wang, Xianhuo; Zhang, Fei; Ji, Wei; Wu, Bing; Han, Jinghua; Zhang, Haichang; Wang, Huaqing; Chang, Jin; Niu, Ruifang

2012-06-01

A functional drug carrier comprised of folic acid modified lipid-shell and polymer-core nanoparticles (FLPNPs) including poly(D,L-lactide-co-glycolide) (PLGA) core, PEGylated octadecyl-quaternized lysine modified chitosan (PEG-OQLCS) as lipid-shell, folic acid as targeting ligand and cholesterol was prepared and evaluated for targeted delivery of paclitaxel (PTX). Confocal microscopy analysis confirmed the coating of the lipid-shell on the polymer-core. Physicochemical characterizations of FLPNPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. The internalization efficiency and targeting ability of FLPNPs were demonstrated by flow cytometry and confocal microscopy. PTX loaded FLPNPs showed a significantly higher cytotoxicity than the commercial PTX formulation (Taxol®). The intravenous administration of PTX encapsulated FLPNPs led to tumor regression and improvement of animal survival in a murine model, compared with that observed with Taxol® and biodistribution study showed that PTX concentration in tumor for PTX encapsulated FLPNPs was higher than other PTX formulations. Our data indicate that PTX loaded FLPNPs are a promising nano-sized drug formulation for cancer therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Efficient antitumor effect of co-drug-loaded nanoparticles with gelatin hydrogel by local implantation

PubMed Central

Zhang, Hao; Tian, Yong; Zhu, Zhenshu; Xu, Huae; Li, Xiaolin; Zheng, Donghui; Sun, Weihao

2016-01-01

Tetrandrine (Tet) could enhance the antitumor effect of Paclitaxel (Ptx) by increasing intracellular Reactive Oxygen Species (ROS) levels, which leads to the possibility of co-delivery of both drugs for synergistic antitumor effect. In the current study, we reported an efficient, local therapeutic strategy employing effective Tet and Ptx delivery with a nanoparticle-loaded gelatin system. Tet- and Ptx co-loaded mPEG-PCL nanoparticles (P/T-NPs) were encapsulated into the physically cross-linked gelatin hydrogel and then implanted on the tumor site for continuous drug release. The drug-loaded gelatin hydrogel underwent a phase change when the temperature slowly increased. In vitro study showed that Tet/Ptx-loaded PEG-b-PCL nanoparticles encapsulated within a gelatin hydrogel (P/T-NPs-Gelatin) inhibited the growth and invasive ability of BGC-823 cells more effectively than the combination of free drugs or P/T-NPs. In vivo study validated the therapeutic potential of P/T-NPs-Gelatin. P/T-NPs-Gelatin significantly inhibited the activation of p-Akt and the downstream anti-apoptotic Bcl-2 protein and also inducing the activation of pro-apoptotic Bax protein. Moreover, the molecular-modulating effect of P/T-NPs-Gelatin on related proteins varied slightly under the influence of NAC, which was supported by the observations of the tumor volumes and weights. Based on these findings, local implantation of P/T-NPs-Gelatin may be a promising therapeutic strategy for the treatment of gastric cancer. PMID:27226240

Fluorescence imaging of antibiotic clofazimine encapsulated within mesoporous silica particle carriers: relevance to drug delivery and the effect on its release kinetics.

PubMed

Angiolini, Lorenzo; Valetti, Sabrina; Cohen, Boiko; Feiler, Adam; Douhal, Abderrazzak

2018-05-03

We report on the encapsulation of the antibiotic clofazimine (CLZ) within the pores of mesoporous silica particles having hydrophilic (CBET value of 137) and more hydrophobic (CBET value of 94 after calcination at 600 °C) surfaces. We studied the effect of pH on the released amount of CLZ in aqueous solutions and observed a maximum at pH 4.1 in correlation with the solubility of the drug. Less release of the drug was observed from the more hydrophobic particles which was attributed to a difference in the affinity of the drug to the carrier particles. Fluorescence lifetime imaging microscopy, emission spectra, and fluorescence lifetimes of single drug loaded particles provided detailed understanding and new knowledge of the physical form of the encapsulated drug and the distribution within the particles. The distribution of CLZ within the particles was independent of the surface chemistry of the particles. The confirmation of CLZ molecules as monomers or aggregates was revealed by controlled removal of the drug with solvent. Additionally, the observed optical "halo effect" in the fluorescent images was interpreted in terms of specific quenching of high concentration of molecules. The emission lifetime experiments suggest stronger interaction of CLZ with the more hydrophobic particles, which is relevant to its release. The results reported in this work demonstrate that tuning the hydrophilicity/hydrophobicity of mesoporous silica particles can be used as a tool to control the release without impacting their loading ability.

Investigation of Carrageenan Aerogel Microparticles as a Potential Drug Carrier.

PubMed

Obaidat, Rana M; Alnaief, Mohammad; Mashaqbeh, Hadeia

2018-05-07

Carrageenan is an anionic polysaccharide offering many advantages to be used in drug delivery applications. These include availability, thermo-stability, low toxicity, and encapsulating properties. Combination of these properties with aerogel properties like large surface area and porosity make them an ideal candidate for drug adsorption and delivery applications. Emulsion-gelation technique was used to prepare carrageenan gel microparticles with supercritical CO 2 for drying and loading purposes. Ibuprofen has been selected as a model drug for drug loading inside. The prepared microparticles were characterized using particle size analysis, X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, density measurements, surface area, and porosity measurements. Finally, dissolution was applied to the loaded preparations to test in vitro drug release. Ibuprofen was successfully loaded in the amorphous form inside the prepared microparticles with a significant enhancement in the drug release profile. In conclusion, prepared carrageenan aerogel microparticles showed an excellent potential for use as a drug carrier.

In Situ Loading of Drugs into Mesoporous Silica SBA-15.

PubMed

Wan, Mi Mi; Li, Yan Yan; Yang, Tian; Zhang, Tao; Sun, Xiao Dan; Zhu, Jian Hua

2016-04-25

In a new strategy for loading drugs into mesoporous silica, a hydrophilic (heparin) or hydrophobic drug (ibuprofen) is encapsulated directly in a one-pot synthesis by evaporation-induced self-assembly. In situ drug loading significantly cuts down the preparation time and dramatically increases the loaded amount and released fraction of the drug, and appropriate drug additives favor a mesoporous structure of the vessels. Drug loading was verified by FTIR spectroscopy and release tests, which revealed much longer release with a larger amount of heparin or ibuprofen compared to postloaded SBA-15. Besides, the in vitro anticoagulation properties of the released heparin and the biocompatibility of the vessels were carefully assessed, including activated partial thromboplastin time, thrombin time, hemolysis, platelet adhesion experiments, and the morphologies of red blood cells. A concept of new drug-release agents with soft core and hard shell is proposed and offers guidance for the design of novel drug-delivery systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hydroxypropyl-β-cyclodextrin for Delivery of Baicalin via Inclusion Complexation by Supercritical Fluid Encapsulation.

PubMed

Li, Ying; He, Zhen-Dan; Zheng, Qian-En; Hu, Chengshen; Lai, Wing-Fu

2018-05-14

Over the years, various methods have been developed to enhance the solubility of insoluble drugs; however, most of these methods are time-consuming and labor intensive or involve the use of toxic materials. A method that can safely and effectively enhance the solubility of insoluble drugs is lacking. This study adopted baicalin as an insoluble drug model, and used hydroxypropyl-β-cyclodextrin for the delivery of baicalin via the inclusion complexation by supercritical fluid encapsulation. Different parameters for the complex preparation as well as the physicochemical properties of the complex have been investigated. Our results showed that when compared to the conventional solution mixing approach, supercritical fluid encapsulation enables a more precise control of the properties of the complex, and gives higher loading and encapsulation efficiency. It is anticipated that our reported method can be useful in enhancing the preparation efficiency of inclusion complexes, and can expand the application potential of insoluble herbal ingredients in treatment development and pharmaceutical formulation.

PNIPAAm-MAA nanoparticles as delivery vehicles for curcumin against MCF-7 breast cancer cells.

PubMed

Zeighamian, Vahideh; Darabi, Masoud; Akbarzadeh, Abolfazl; Rahmati-Yamchi, Mohammad; Zarghami, Nosratollah; Badrzadeh, Fariba; Salehi, Roya; Mirakabad, Fatemeh Sadat Tabatabaei; Taheri-Anganeh, Mortaza

2016-01-01

Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm-MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

Formation of methotrexate-PLLA-PEG-PLLA composite microspheres by microencapsulation through a process of suspension-enhanced dispersion by supercritical CO2

PubMed Central

Chen, Ai-Zheng; Wang, Guang-Ya; Wang, Shi-Bin; Li, Li; Liu, Yuan-Gang; Zhao, Chen

2012-01-01

Background The aim of this study was to improve the drug loading, encapsulation efficiency, and sustained-release properties of supercritical CO2-based drug-loaded polymer carriers via a process of suspension-enhanced dispersion by supercritical CO2 (SpEDS), which is an advanced version of solution-enhanced dispersion by supercritical CO2 (SEDS). Methods Methotrexate nanoparticles were successfully microencapsulated into poly (L-lactide)-poly(ethylene glycol)-poly(L-lactide) (PLLA-PEG-PLLA) by SpEDS. Methotrexate nanoparticles were first prepared by SEDS, then suspended in PLLA-PEG-PLLA solution, and finally microencapsulated into PLLA-PEG-PLLA via SpEDS, where an “injector” was utilized in the suspension delivery system. Results After microencapsulation, the composite methotrexate (MTX)-PLLA-PEG-PLLA microspheres obtained had a mean particle size of 545 nm, drug loading of 13.7%, and an encapsulation efficiency of 39.2%. After an initial burst release, with around 65% of the total methotrexate being released in the first 3 hours, the MTX-PLLA-PEG-PLLA microspheres released methotrexate in a sustained manner, with 85% of the total methotrexate dose released within 23 hours and nearly 100% within 144 hours. Conclusion Compared with a parallel study of the coprecipitation process, microencapsulation using SpEDS offered greater potential to manufacture drug-loaded polymer microspheres for a drug delivery system. PMID:22787397

Synthesis and characterization of chitosan quaternary ammonium salt and its application as drug carrier for ribavirin.

PubMed

Li, Si-Dong; Li, Pu-Wang; Yang, Zi-Ming; Peng, Zheng; Quan, Wei-Yan; Yang, Xi-Hong; Yang, Lei; Dong, Jing-Jing

2014-11-01

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) is hydro-soluble chitosan (CS) derivative, which can be obtained by the reaction between epoxypropyl trimethyl ammonium chloride (ETA) and CS. The preparation parameters for the synthesis of HTCC were optimized by orthogonal experimental design. ETA was successfully grafted into the free amino group of CS. Grafting of ETA with CS had great effect on the crystal structure of HTCC, which was confirmed by the XRD results. HTCC displayed higher capability to form nanoparticles by crosslinking with negatively charged sodium tripolyphosphate (TPP). Ribavrin- (RIV-) loaded HTCC nanoparticles were positively charged and were spherical in shape with average particle size of 200 nm. More efficient drug encapsulation efficiency and loading capacity were obtained for HTCC in comparison with CS, however, HTCC nanoparticles displayed faster release rate due to its hydro-soluble properties. The results suggest that HTCC is a promising CS derivative for the encapsulation of hydrophilic drugs in obtaining sustained release of drugs.

Characteristics of Artemether-Loaded Poly(lactic-co-glycolic) Acid Microparticles Fabricated by Coaxial Electrospray: Validation of Enhanced Encapsulation Efficiency and Bioavailability.

PubMed

Mangrio, Farhana Akbar; Dwivedi, Pankaj; Han, Shuya; Zhao, Gang; Gao, Dayong; Si, Ting; Xu, Ronald X

2017-12-04

Artemether is one of the most effective drugs for the treatment of chloroquine-resistant and Plasmodium falciparum strains of malaria. However, its therapeutic potency is hindered by its poor bioavailability. To overcome this limitation, we have encapsulated artemether in poly(lactic-co-glycolic) acid (PLGA) core-shell microparticles (MPs) using the coaxial electrospray method. With optimized process parameters including liquid flow rates and applied electric voltages, experiments are systematically carried out to generate a stable cone-jet mode to produce artemether-loaded PLGA-MPs with an average size of 2 μm, an encapsulation efficiency of 78 ± 5.6%, and a loading efficiency of 11.7%. The in vitro release study demonstrates the sustained release of artemether from the core-shell structure in comparison with that of plain artemether and that of MPs produced by single-axial electrospray without any relevant cytotoxicity. The in vivo studies are performed to evaluate the pharmacokinetic characteristics of the artemether-loaded PLGA-MPs. Our study implies that artemether can be effectively encapsulated in a protective shell of PLGA for controlled release kinetics and enhanced oral bioavailability.

Assessment of formulated amodiaquine microparticles in Leishmania donovani infected rats.

PubMed

Nettey, Henry; Allotey-Babington, Grace Lovia; Somuah, Isaac; Banga, N'guessan Benoit; Afrane, Barima; Amponsah, Seth Kwabena; Annor, Henrietta; Darko, Henry; Hanson, Kwame; Aidoo, Anoa; Broni, Marisa Nyarkoa; Sasu, Clement; Nyarko, Alexander

2017-02-01

The aim of this study was to formulate, characterise and evaluate the activity of amodiaquine microparticles against Leishmania donovani. Microparticles were formulated by encapsulating the drug in bovine serum albumin using the spray-dryer method. The microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency and in vitro release profile. The size range of the microparticles formulated was between 1.9 and 10 μm with an average zeta potential of -25.5 mV. Of the expected 20% drug loading, an average of 18.27% was obtained giving an encapsulation efficiency of 91.35%. Pharmacokinetic profile of amodiaquine improved with microencapsulation of the drug with C max , AUC 0→48 and t 1//2 all significantly higher than amodiaquine solution. Amodiaquine microparticles showed an overall higher bioavailability and hence were more effective in eliminating intra-tissue parasites than the drug solution. It would therefore be expected that the formulated microparticles will be more effective in treating visceral leishmaniasis.

Enhanced drug encapsulation and extended release profiles of calcium-alginate nanoparticles by using tannic acid as a bridging cross-linking agent.

PubMed

Abulateefeh, Samer R; Taha, Mutasem O

2015-01-01

Calcium alginate nanoparticles (NPs) suffer from sub-optimal stability in bio-relevant media leading to low drug encapsulation efficiency and uncontrolled release profiles. To sort out these drawbacks, a novel approach is proposed herein based on introducing tannic acid into these NPs to act as a bridging cross-linking aid agent. Calcium-alginate NPs were prepared by the ionotropic gelation method and loaded with diltiazem hydrochloride as a model drug. These NPs were characterized in terms of particle size, zeta potential, and morphology, and results were explained in accordance with Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The incorporation of tannic acid led to more than four folds increase in drug encapsulation efficiency (i.e. from 15.3% to 69.5%) and reduced burst drug release from 44% to around 10% within the first 30 min. These findings suggest the possibility of improving the properties of Ca-alginate NPs by incorporating cross-linking aid agents under mild conditions.

PEGylated lipid nanocapsules with improved drug encapsulation and controlled release properties.

PubMed

Hervella, Pablo; Alonso-Sande, Maria; Ledo, Francisco; Lucero, Maria L; Alonso, Maria J; Garcia-Fuentes, Marcos

2014-01-01

Drugs with poor lipid and water solubility are some of the most challenging to formulate in nanocarriers, typically resulting in low encapsulation efficiencies and uncontrolled release profiles. PEGylated nanocapsules (PEG-NC) are known for their amenability to diverse modifications that allow the formation of domains with different physicochemical properties, an interesting feature to address a drug encapsulation problem. We explored this problem by encapsulating in PEG-NC the promising anticancer drug candidate F10320GD1, used herein as a model for compounds with such characteristics. The nanocarriers were prepared from Miglyol(®), lecithin and PEG-sterate through a solvent displacement technique. The resulting system was a homogeneous suspension of particles with size around 200 nm. F10320GD1 encapsulation was found to be very poor (<15%) if PEG-NC were prepared using water as continuous phase; but we were able to improve this value to 85% by fixing the pH of the continuous phase to 9. Interestingly, this modification also improved the controlled release properties and the chemical stability of the formulation during storage. These differences in pharmaceutical properties together with physicochemical data suggest that the pH of the continuous phase used for PEG-NC preparation can modify drug allocation, from the external shell towards the inner lipid core of the nanocapsules. Finally, we tested the bioactivity of the drug-loaded PEG-NC in several tumor cell lines, and also in endothelial cells. The results indicated that drug encapsulation led to an improvement on drug cytotoxicity in tumor cells, but not in non-tumor endothelial cells. Altogether, the data confirms that PEG-NC show adequate delivery properties for F10320GD1, and underlines its possible utility as an anticancer therapy.

Silymarin-Loaded Nanoparticles Based on Stearic Acid-Modified Bletilla striata Polysaccharide for Hepatic Targeting.

PubMed

Ma, Yanni; He, Shaolong; Ma, Xueqin; Hong, Tongtong; Li, Zhifang; Park, Kinam; Wang, Wenping

2016-02-29

Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products, especially for liver-targeting purposes. In this study, silymarin was encapsulated in self-assembled nanoparticles of Bletilla striata polysaccharide (BSP) conjugates modified with stearic acid and the physicochemical properties of the obtained nanoparticles were characterized. The silymarin-loaded micelles appeared as spherical particles with a mean diameter of 200 nm under TEM. The encapsulation of drug molecules was confirmed by DSC thermograms and XRD diffractograms, respectively. The nanoparticles exhibited a sustained-release profile for nearly 1 week with no obvious initial burst. Compared to drug solutions, the drug-loaded nanoparticles showed a lower viability and higher uptake intensity on HepG2 cell lines. After intravenous administration of nanoparticle formulation for 30 min to mice, the liver became the most significant organ enriched with the fluorescent probe. These results suggest that BSP derivative nanoparticles possess hepatic targeting capability and are promising nanocarriers for delivering silymarin to the liver.

Brain targeted nanoparticulate drug delivery system of rasagiline via intranasal route.

PubMed

Mittal, Deepti; Md, Shadab; Hasan, Quamrul; Fazil, Mohammad; Ali, Asgar; Baboota, Sanjula; Ali, Javed

2016-01-01

The aim of the present study was to prepare and evaluate a rasagiline-loaded chitosan glutamate nanoparticles (RAS-CG-NPs) by ionic gelation of CG with tripolyphosphate anions (TPP). RAS-loaded CG-NPs were characterized for particle size, size distribution, encapsulation efficiency and in vitro drug release. The mean particles size, polydispersity index (PDI) and encapsulation efficiency was found to be 151.1 ± 10.31, 0.380 ± 0.01 and 96.43 ± 4.23, respectively. Biodistribution of RAS formulations in the brain and blood of mice following intranasal (i.n.) and intravenous (i.v.) administration was performed using HPLC analytical method. The drug concentrations in brain following the i.n. of CG-NPs were found to be significantly higher at all the time points compared to both drug (i.n.) and drug CG-NPs (i.v.). The Cmax (999.25 ng/ml) and AUC (2086.60 ng h/ml) of formulation CG-NPs (i.n) were found to be significantly higher than CG-NPs (i.v.) and RAS solution (i.n.). The direct transport percentage (DTP%) values of RAS-loaded CG-NPs (i.n.) as compared to drug solution (i.n.) increased from 66.27 ± 1.8 to 69.27 ± 2.1%. The results showed significant enhancement of bioavailability in brain, after administration of the RAS-loaded CG-NPs which could be a substantial achievement of direct nose to brain targeting in Parkinson's disease therapy.

Microparticles Produced by the Hydrogel Template Method for Sustained Drug Delivery

PubMed Central

Lu, Ying; Sturek, Michael; Park, Kinam

2014-01-01

Polymeric microparticles have been used widely for sustained drug delivery. Current methods of microparticle production can be improved by making homogeneous particles in size and shape, increasing the drug loading, and controlling the initial burst release. In the current study, the hydrogel template method was used to produce homogeneous poly(lactide-co-glycolide) (PLGA) microparticles and to examine formulation and process-related parameters. Poly(vinyl alcohol) (PVA) was used to make hydrogel templates. The parameters examined include PVA molecular weight, type of PLGA (as characterized by lactide content, inherent viscosity), polymer concentration, drug concentration and composition of solvent system. Three model compounds studied were risperidone, methylprednisolone acetate and paclitaxel. The ability of the hydrogel template method to produce microparticles with good conformity to template was dependent on molecular weight of PVA and viscosity of the PLGA solution. Drug loading and encapsulation efficiency were found to be influenced by PLGA lactide content, polymer concentration and composition of the solvent system. The drug loading and encapsulation efficiency were 28.7% and 82% for risperidone, 31.5% and 90% for methylprednisolone acetate, and 32.2 % and 92 % for paclitaxel, respectively. For all three drugs, release was sustained for weeks, and the in vitro release profile of risperidone was comparable to that of microparticles prepared using the conventional emulsion method. The hydrogel template method provides a new approach of manipulating microparticles. PMID:24333903

Multilayer encapsulated mesoporous silica nanospheres as an oral sustained drug delivery system for the poorly water-soluble drug felodipine.

PubMed

Hu, Liang; Sun, Hongrui; Zhao, Qinfu; Han, Ning; Bai, Ling; Wang, Ying; Jiang, Tongying; Wang, Siling

2015-02-01

We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers. Copyright © 2014 Elsevier B.V. All rights reserved.

Curcumin drug delivery by vanillin-chitosan coated with calcium ferrite hybrid nanoparticles as carrier.

PubMed

Kamaraj, Sriram; Palanisamy, Uma Maheswari; Kadhar Mohamed, Meera Sheriffa Begum; Gangasalam, Arthanareeswaran; Maria, Gover Antoniraj; Kandasamy, Ruckmani

2018-04-30

The aim of the present investigation is the development, optimization and characterization of curcumin-loaded hybrid nanoparticles of vanillin-chitosan coated with super paramagnetic calcium ferrite. The functionally modified vanillin-chitosan was prepared by the Schiff base reaction to enhance the hydrophobic drug encapsulation efficiency. Calcium ferrite (CFNP) nano particles were added to the vanillin modified chitosan to improve the biocompatibility. The vanillin-chitosan-CFNP, hybrid nanoparticle carrier was obtained by ionic gelation method. Characterizations of the hybrid materials were performed by XRD, FTIR, 1 H NMR, TGA, AFM and SEM techniques to ensure the modifications on the chitosan material. Taguchi method was applied to optimize the drug (curcumin) encapsulation efficiency by varying the drug to chitosan-vanillin, CFNP to chitosan-vanillin and TPP (sodium tripolyphospate) to chitosan-vanillin ratios. The maximum encapsulation efficiency was obtained as 98.3% under the conditions of 0.1, 0.75 and 1.0 for the drug to chitosan-vanillin, CFNP to chitosan-vanillin and TPP to chitosan-vanillin ratios, respectively. The curcumin release was performed at various pH, initial drug loading concentrations and magnetic fields. The drug release mechanism was predicted by fitting the experimental kinetic data with various drug release models. The drug release profiles showed the best fit with Higuchi model under the most of conditions. The drug release mechanism followed both non-Fickian diffusion and case II transport mechanism for chitosan, however the non-Fickian diffusion mechanism was followed for the vanillin modified chitosan. The biocompatibility of the hybrid material was tested using L929 fibroblast cells. The cytotoxicity test was performed against MCF-7 breast cancer cell line to check the anticancer property of the hybrid nano carrier with the curcumin drug. Copyright © 2018 Elsevier B.V. All rights reserved.

Combined Cancer Therapy with Hyaluronan-Decorated Fullerene-Silica Multifunctional Nanoparticles to Target Cancer Stem-Like Cells

PubMed Central

Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

2016-01-01

Cancer stem-like cells (CSCs) are resistant to chemotherapy and highly tumorigenic, which contributes to tumor occurrence and post-treatment relapse. We developed a novel C60 fullerene-silica nanoparticle system surface-decorated with hyaluronan (HA) to target the variant CD44 overexpressed on breast CSCs. Furthermore, doxorubicin hydrochloride (DOX) and indocyanine green (ICG) can be encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (> 90%) and loading content (e.g., 48.5% at a drug-to-nanoparticle feeding ratio of 1:1, compared to the commonly used drug-to-nanoparticle feeding ratio of 1:20 with a drug loading content of less than 5%). As a result, the DOX and ICG-laden nanoparticles can be used as a single nanoplatform to achieve combined chemo, photodynamic, and photothermal therapy under near infrared laser irradiation for effective destruction of the breast CSCs both in vitro and in vivo, with no evident systemic toxicity. Moreover, we found the nanoparticles with a higher drug loading content (e.g., 48.5 versus 4.6%) also have significantly higher antitumor efficacy, given the same total drug dose. These results demonstrate the great potential of the multifunctional hybrid nanoparticle system for augmenting cancer therapy by eliminating the CSCs. PMID:27162075

Dorzolamide-loaded PLGA/vitamin E TPGS nanoparticles for glaucoma therapy: Pharmacoscintigraphy study and evaluation of extended ocular hypotensive effect in rabbits.

PubMed

Warsi, Musarrat H; Anwar, Mohammed; Garg, Vaidehi; Jain, Gaurav K; Talegaonkar, Sushama; Ahmad, Farhan J; Khar, Roop K

2014-10-01

Poor drug penetration and rapid clearance after topical instillation of a drug formulation into the eyes are the major causes for the lower ocular bioavailability from conventional eye drops. Along with this, poor encapsulation efficiency of hydrophilic drug in polymeric nanoparticles remains a major formulation challenge. Taking this perspective into consideration, dorzolamide (DZ)-loaded PLGA nanoparticles were developed employing two different emulsifiers (PVA and vitamin E TPGS) and the effects of various formulation and process variables on particle size and encapsulation efficiency were assessed. Nanoparticles emulsified with vitamin E TPGS (DZ-T-NPs) were found to possess enhanced drug encapsulation (59.8±6.1%) as compared to those developed with PVA as emulsifier (DZ-P-NPs). Transcorneal permeation study revealed a significant enhancement in permeation (1.8-2.5 fold) as compared to solution. In addition, ex vivo biodistribution study showed a higher concentration of drug in the aqueous humour (1.5-2.3 fold). Histological and IR-camera studies proved the non-irritant potential of the formulations. Pharmacoscintigraphic studies revealed the reduced corneal clearance, as well as naso-lachrymal drainage in comparison to drug solution. Furthermore, efficacy study revealed that DZ-P-NPs and DZ-T-NPs significantly reduced the intraocular pressure by 22.81% and 29.12%, respectively, after a single topical instillation into the eye. Copyright © 2014 Elsevier B.V. All rights reserved.

Mesoporous silica nanocarriers encapsulated antimalarials with high therapeutic performance.

PubMed

Amolegbe, Saliu Alao; Hirano, Yui; Adebayo, Joseph Oluwatope; Ademowo, Olusegun George; Balogun, Elizabeth Abidemi; Obaleye, Joshua Ayoola; Krettli, Antoniana Ursine; Yu, Chengzhong; Hayami, Shinya

2018-02-15

The use of nanocarriers in drug delivery is a breakeven research and has received a clarion call in biomedicine globally. Herein, two newly nano-biomaterials: MCM-41 encapsulated quinine (MCM-41 ⊃ QN) (1) and 3-phenylpropyl silane functionalized MCM-41 loaded QN (pMCM-41 ⊃ QN) (2) were synthesized and well characterized. 1 and 2 along with our two already reported nano-antimalarial drugs (MCM-41 ⊃ ATS) (3) and 3-aminopropyl silane functionalized MCM-41 contained ATS (aMCM-41 ⊃ ATS) (4) were screened in vitro for their activity against P. falciparium W2 strain, cytotoxicity against BGM cells and in vivo for their activity against Plasmodium bergheiNK65. 1 has the highest antimalarial activity in vivo against P. berghei NK65, (ED 50 : < 0.0625 mg/kg body weight) and higher mean survival time compared to the other nano biomaterials or unencapsulated drugs at doses higher than 0.0625 mg/kg body weight. This encapsulation strategy of MCM-41 ⊃ QN (1) stands very useful and effective in delivering the drug to the target cells compared to other delivery systems and therefore, this encapsulated drug may be considered for rational drug design.

Inhibition of tracheal vascular extravasation by liposome-encapsulated albuterol in rats.

PubMed

Zhang, W; Guo, L; Nadel, J A; Papahadjopoulos, D

1998-03-01

To develop a liposome-based system for systemic delivery of anti-inflammatory drugs to airways and other inflamed tissues. Postcapillary venular gap junctions open during airway inflammation and allow fluid accumulation and permit molecules (e.g. complement, kininogen) to enter tissues, initiating inflammatory cascades. Beta-adrenergic agonists prevent inflammatory plasma extravasation, but because of their deleterious side effects, they are not used intravenously. When sterically stabilized "stealth" liposomes are injected i.v., they remain in the circulation for long periods. Inflammatory mediators [e.g., substance P(SP)] open postcapillary venular gaps and allow liposomes and their contents to be deposited selectively in the inflamed tissue. We hypothesized that liposomes encapsulating a beta-adrenergic agonist, such as albuterol, would deposit selectively in inflamed airway tissue, where the drug would slowly leak out of the liposomes, resulting in closure of the gaps, thus preventing subsequent inflammatory extravasation. To test this hypothesis, we delivered albuterol-loaded liposomes i.v. in rats. Then we injected SP to open the venular gaps and allow accumulation of the drug-loaded liposomes in airway tissue. We examined whether this treatment resulted in inhibition of subsequent plasma extravasation induced by SP. The results indicate that liposome-encapsulated albuterol inhibits subsequent extravasation, presumably by leaking out of liposomes in airway tissue. This inhibition occurs for prolonged periods of time and with limited side effects compared to the effect of free albuterol. We conclude that liposomes loaded with appropriate drugs, by migrating to inflamed tissue and subsequently inhibiting inflammatory cascades, may be of therapeutic value in inflammatory diseases.

Structure-directing star-shaped block copolymers: supramolecular vesicles for the delivery of anticancer drugs.

PubMed

Yang, Chuan; Liu, Shao Qiong; Venkataraman, Shrinivas; Gao, Shu Jun; Ke, Xiyu; Chia, Xin Tian; Hedrick, James L; Yang, Yi Yan

2015-06-28

Amphiphilic polycarbonate/PEG copolymer with a star-like architecture was designed to facilitate a unique supramolecular transformation of micelles to vesicles in aqueous solution for the efficient delivery of anticancer drugs. The star-shaped amphipilic block copolymer was synthesized by initiating the ring-opening polymerization of trimethylene carbonate (TMC) from methyl cholate through a combination of metal-free organo-catalytic living ring-opening polymerization and post-polymerization chain-end derivatization strategies. Subsequently, the self-assembly of the star-like polymer in aqueous solution into nanosized vesicles for anti-cancer drug delivery was studied. DOX was physically encapsulated into vesicles by dialysis and drug loading level was significant (22.5% in weight) for DOX. Importantly, DOX-loaded nanoparticles self-assembled from the star-like copolymer exhibited greater kinetic stability and higher DOX loading capacity than micelles prepared from cholesterol-initiated diblock analogue. The advantageous disparity is believed to be due to the transformation of micelles (diblock copolymer) to vesicles (star-like block copolymer) that possess greater core space for drug loading as well as the ability of such supramolecular structures to encapsulate DOX. DOX-loaded vesicles effectively inhibited the proliferation of 4T1, MDA-MB-231 and BT-474 cells, with IC50 values of 10, 1.5 and 1.0mg/L, respectively. DOX-loaded vesicles injected into 4T1 tumor-bearing mice exhibited enhanced accumulation in tumor tissue due to the enhanced permeation and retention (EPR) effect. Importantly, DOX-loaded vesicles demonstrated greater tumor growth inhibition than free DOX without causing significant body weight loss or cardiotoxicity. The unique ability of the star-like copolymer emanating from the methyl cholate core provided the requisite modification in the block copolymer interfacial curvature to generate vesicles of high loading capacity for DOX with significant kinetic stability that have potential for use as an anti-cancer drug delivery carrier for cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation of microcapsules with self-microemulsifying core by a vibrating nozzle method.

PubMed

Homar, Miha; Suligoj, Dasa; Gasperlin, Mirjana

2007-02-01

Incorporation of drugs in self-microemulsifying systems (SMES) offers several advantages for their delivery, the main one being faster drug dissolution and absorption. Formulation of SMES in solid dosage forms can be difficult and, to date, most SMES are applied in liquid dosage form or soft gelatin capsules. This study has explored the incorporation of SMES in microcapsules, which could then be used for formulation of solid dosage forms. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to produce alginate microcapsules with a self-microemulsifying core. Retention of the core phase was improved by optimization of encapsulator parameters and modification of the shell forming phase and hardening solution. The mean encapsulation efficiency of final batches was more than 87%, which resulted in 0.07% drug loading. It was demonstrated that production of microcapsules with a self-microemulsifying core is possible and that the process is stable and reproducible.

Internalized compartments encapsulated nanogels for targeted drug delivery

NASA Astrophysics Data System (ADS)

Yu, Jicheng; Zhang, Yuqi; Sun, Wujin; Wang, Chao; Ranson, Davis; Ye, Yanqi; Weng, Yuyan; Gu, Zhen

2016-04-01

Drug delivery systems inspired by natural particulates hold great promise for targeted cancer therapy. An endosome formed by internalization of plasma membrane has a massive amount of membrane proteins and receptors on the surface, which is able to specifically target the homotypic cells. Herein, we describe a simple method to fabricate an internalized compartments encapsulated nanogel with endosome membrane components (EM-NG) from source cancer cells. Following intracellular uptake of methacrylated hyaluronic acid (m-HA) adsorbed SiO2/Fe3O4 nanoparticles encapsulating a crosslinker and a photoinitiator, EM-NG was readily prepared through in situ crosslinking initiated under UV irradiation after internalization. The resulting nanogels loaded with doxorubicin (DOX) displayed enhanced internalization efficiency to the source cells through a specific homotypic affinity in vitro. However, when treated with the non-source cells, the EM-NGs exhibited insignificant difference in therapeutic efficiency compared to a bare HA nanogel with DOX. This study illustrates the potential of utilizing an internalized compartments encapsulated formulation for targeted cancer therapy, and offers guidelines for developing a natural particulate-inspired drug delivery system.Drug delivery systems inspired by natural particulates hold great promise for targeted cancer therapy. An endosome formed by internalization of plasma membrane has a massive amount of membrane proteins and receptors on the surface, which is able to specifically target the homotypic cells. Herein, we describe a simple method to fabricate an internalized compartments encapsulated nanogel with endosome membrane components (EM-NG) from source cancer cells. Following intracellular uptake of methacrylated hyaluronic acid (m-HA) adsorbed SiO2/Fe3O4 nanoparticles encapsulating a crosslinker and a photoinitiator, EM-NG was readily prepared through in situ crosslinking initiated under UV irradiation after internalization. The resulting nanogels loaded with doxorubicin (DOX) displayed enhanced internalization efficiency to the source cells through a specific homotypic affinity in vitro. However, when treated with the non-source cells, the EM-NGs exhibited insignificant difference in therapeutic efficiency compared to a bare HA nanogel with DOX. This study illustrates the potential of utilizing an internalized compartments encapsulated formulation for targeted cancer therapy, and offers guidelines for developing a natural particulate-inspired drug delivery system. Electronic supplementary information (ESI) available: Synthesis of m-HA; synthesis of rhodamine-HA derivative; supplementary data on relative fluorescence intensity of DOX-EN-NGs on HeLa cells. See DOI: 10.1039/c5nr08895j

Anacardic acid enhances the anticancer activity of liposomal mitoxantrone towards melanoma cell lines – in vitro studies

PubMed Central

Legut, Mateusz; Lipka, Dominik; Filipczak, Nina; Piwoni, Adriana; Kozubek, Arkadiusz; Gubernator, Jerzy

2014-01-01

This paper describes a novel formulation of antineoplastic drug: mitoxantrone loaded into liposomal carriers enriched with encapsulated anacardic acid in the liposomal bilayer using a vitamin C gradient. Anacardic acid is a potent epigenetic agent with anticancer activity. This is the first liposomal formulation to combine an actively encapsulated drug and anacardic acid. The liposomes were characterized in terms of basic parameters, such as size, zeta potential, optimal drug-to-lipid ratio, loading time and temperature, and stability at 4°C and in human plasma in vitro. The formulation was found to be stable, and the loading process was rapid and efficient (drug-to-lipid ratio of up to 0.3 with over 90% efficiency in 5 minutes). The cytotoxicity of these formulations was assessed using the human melanoma cell lines A375 and Hs294T and the normal human dermal fibroblast line. The results showed that anacardic acid and to a smaller extent vitamin C significantly increased the cytotoxicity of the drug towards melanoma compared to ammonium sulfate liposomes. On the other hand, vitamin C and anacardic acid both protected normal cells from damage caused by the drug. The formulation combining anacardic acid, vitamin C, and mitoxantrone showed promising results in terms of cytotoxicity and cytoprotection. Therefore, it has potential for anticancer treatment. PMID:24489469

Development and optimization of doxorubicin loaded poly(lactic-co-glycolic acid) nanobubbles for drug delivery into HeLa cells.

PubMed

Deng, Liwei; Li, Li; Yang, Hong; Li, Li; Zhao, Fenglong; Wu, Chunhui; Liu, Yiyao

2014-04-01

Microbubbles (MBs, usually 2-8 microm) as ultrasound contrast agent and drug carrier are promising for ultrasonic imaging and drug delivery. However, MBs posed some limitations due to their large diameters. In the current study, we developed a nanoscale bubbles (nanobubbles, NBs) by encapsulating the doxorubicin (DOX) into poly(lactic-co-glycolic acid) (PLGA) shells (denoted as DOX-PLGA NBs) for drug delivery into cancer cells. The size, morphology, particle stability, drug encapsulation efficiency, and drug payload were determined. The results showed that the DOX-PLGA NBs were uniform (270 +/- 3 nm) and spherical with a smooth surface, and were well dispersed and stable in water. The encapsulation efficiency and payload of DOX increased with its initial loading concentrations. The release behavior of DOX from the DOX-PLGA NBs exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release at both pH 7.4 and pH 4.4, and also presented in a pH-triggered releasing profile. The qualitative analysis of cellular internalization into HeLa cells by inverted fluorescence microscope showed that the cellular uptake of DOX-PLGA NBs was both concentration- and time-dependent. Moreover, the cell viability was also investigated using CCK-8 assay. It was found that DOX-PLGA NBs showed greater HeLa cell growth inhibition effect in vitro compared with free DOX. It was concluded that the DOX-PLGA NBs were biocompatible and appropriate for anti-cancer drug delivery, and were potentially promising as a new therapeutic system for cancer treatment.

Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo

NASA Astrophysics Data System (ADS)

Gou, Maling; Men, Ke; Shi, Huashan; Xiang, Mingli; Zhang, Juan; Song, Jia; Long, Jianlin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, Zhiyong

2011-04-01

Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 +/- 0.011) with a mean particle size of 27.3 +/- 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 +/- 1.02%, and drug loading of 12.95 +/- 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t1/2 and AUC of curcuminin vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesisin vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cellsin vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg-1curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

A "ship in a bottle" strategy to load a hydrophilic anticancer drug in porous metal organic framework nanoparticles: efficient encapsulation, matrix stabilization, and photodelivery.

PubMed

di Nunzio, Maria Rosaria; Agostoni, Valentina; Cohen, Boiko; Gref, Ruxandra; Douhal, Abderrazzak

2014-01-23

An essential challenge in the development of nanosized metal organic framework (nanoMOF) materials in biomedicine is to develop a strategy to stabilize their supramolecular structure in biological media while being able to control drug encapsulation and release. We have developed a method to efficiently encapsulate topotecan (TPT, 1), an important cytotoxic drug, in biodegradable nanoMOFs. Once inside the pores, 1 monomers aggregate in a "ship in a bottle" fashion, thus filling practically all of the nanoMOFs' available free volume and stabilizing their crystalline supramolecular structures. Highly efficient results have been found with the human pancreatic cell line PANC1, in contrast with free 1. We also demonstrate that one- and two-photon light irradiation emerges as a highly promising strategy to promote stimuli-dependent 1 release from the nanoMOFs, hence opening new standpoints for further developments in triggered drug delivery.

Nanoformulation for anticancer drug delivery: Enhanced pharmacokinetics and circulation

NASA Astrophysics Data System (ADS)

Parekh, Gaurav

In this study, we have explored the application of the Layer-by-Layer (LbL) assembly technique for improving injectable drug delivery systems of low soluble anticancer drugs (e.g. Camptothecin (CPT), Paclitaxel (PTX) or Doxorubicin (DOX)). For this study, a polyelectrolyte shell encapsulates different types of drug nanocores (e.g. soft core, nanomicelle or solid lipid nanocores).The low soluble drugs tend to crystallize and precipitate in an aqueous medium. This is the reason they cannot be injected and may have low concentrations and low circulation time in the blood. Even though these drugs when present in the cancer microenvironment have high anti-tumor inhibition, the delivery to the tumor site after intravenous administration is a challenge. We have used FDA-approved biopolymers for the process and elaborated formation of 60-90 nm diameter initial cores, which was stabilized by multilayer LbL shells for controlled release and longer circulation. A washless LbL assembly process was applied as an essential advancement in nano-assembly technology using low density nanocore (lipids) and preventing aggregation. This advancement reduced the number of process steps, enhanced drug loading capacity, and prevented the loss of expensive polyelectrolytes. Finally, we elaborated a general nano-encapsulation process, which allowed these three important anticancer drug core-shell nanocapsules with diameters of ca. 100-130 nm (this small size is a record for LbL encapsulation technique) to be stable in the serum and the blood for at least one week, efficient for cancer cell culture studies, injectable to mice with circulation for 4 hrs, and effective in suppressing tumors. This work is divided into three studies. The first study (CHAPTER 4) explores the application of LbL assembly for encapsulating a soft core of albumin protein and CPT anticancer drug. In order to preserve the activity of drug in the core, a unique technique of pH reversal is employed where the first few layers of the LbL shell are assembled at acidic pH 3, and the final layers (2-3) are assembled at a slightly basic pH of 7.4. These LbL-encapsulated nanocores are not stable and immediately aggregate in water or the serum. A final layer of 5 kDa PEG was assembled to improve circulation time. It showed higher colloidal stability in PBS, high drug loading concentration of 0.5 mg/mL, and an improved drug chemical stability in Fetal Bovine Serum with high lactone fraction of 99%. It also showed 3 times improved cytotoxicity against glioblastoma cancer cells. For the first time we applied a new method of the LbL capsule assembly at different pH values, the first 4 bilayers at pH 3, and the following 3 bilayers at pH 7.4. In the second study (CHAPTER 5), the developed LbL assembly for low solubility drug encapsulation was extended for the delivery of PTX loaded in nanomicelle cores. PTX, as a nanomicelle core, is encapsulated with fewer layers of LbL assembly, followed by an extra layer of PEG (PEGylation). A significant improvement was seen in reducing the process steps through reduction in the number of LbL layers, while smaller nano-colloids, ~100 nm, were produced with improved drug loading capacity, higher cytotoxicity, and high mice survival rate. In the third study (CHAPTER 6), we have applied the concepts learned and the techniques developed from the previous two studies to modify the surface of the nanostructured solid lipid carriers (NLC) with LbL architecture, plus extra PEGylation. The NLC are co-loaded with DOX and docosahexaenoic acid (DHA). This study is an attempt to further increase drug circulation time in the blood. We improved the colloidal stability with a narrow distribution size, 128 nm, polydispersity of 0.098, a higher longevity in the blood, a 1.5 times lower accumulation in the liver, a 2.25 times higher accumulation in tumors, and a significant ~3.5 times greater tumor growth inhibition in 4T1 murine tumor model in mice. In conclusion, we developed a general model of an LbL nanoassembly core-shell drug delivery system of three anticancer drugs. The capsules had diameters of ca. 100170 nm, were stable in the serum and the blood for three weeks, were injectable to small animals with a circulation time of 1-4 hrs., and effectively suppressed cancerous tumors in mice.

In vitro and in vivo characterization of doxorubicin and vincristine coencapsulated within liposomes through use of transition metal ion complexation and pH gradient loading.

PubMed

Abraham, Sheela A; McKenzie, Cheryl; Masin, Dana; Ng, Rebecca; Harasym, Troy O; Mayer, Lawrence D; Bally, Marcel B

2004-01-15

There is an opportunity to augment the therapeutic potential of drug combinations through use of drug delivery technology. This report summarizes data obtained using a novel liposomal formulation with coencapsulated doxorubicin and vincristine. The rationale for selecting these drugs is due in part to the fact that liposomal formulations of doxorubicin and vincristine are being separately evaluated as components of drug combinations. Doxorubicin and vincristine were coencapsulated into liposomes using two distinct methods of drug loading. A manganese-based drug loading procedure, which relies on drug complexation with a transition metal, was used to encapsulate doxorubicin. Subsequently the ionophore A23187 was added to induce formation of a pH gradient, which promoted vincristine encapsulation. Plasma elimination studies in mice indicated that the drug:drug ratio before injection [4:1 doxorubicin:vincristine (wt:wt ratio)] changed to 20:1 at the 24-h time point, indicative of more rapid release of vincristine from the liposomes than doxorubicin. Efficacy studies completed in MDA MB-435/LCC6 tumor-bearing mice suggested that at the maximum tolerated dose, the coencapsulated formulation was therapeutically no better than liposomal vincristine. This result was explained in part by in vitro cytotoxicity studies evaluating doxorubicin and vincristine combinations analyzed using the Chou and Talalay median effect principle. These data clearly indicated that simultaneous addition of vincristine and doxorubicin resulted in pronounced antagonism. These results emphasize that in vitro drug combination screens can be used to predict whether a coformulated drug combination will act in an antagonistic or synergistic manner.

Preparation and drug controlled release of porous octyl-dextran microspheres.

PubMed

Hou, Xin; Liu, Yanfei

2015-01-01

In this work, porous octyl-dextran microspheres with excellent properties were prepared by two steps. Firstly, dextran microspheres were synthesized by reversed-phase suspension polymerization. Secondly, octyl-dextran microspheres were prepared by the reaction between dextran microspheres and ethylhexyl glycidyl ether and freezing-drying method. Porous structure of microspheres was formed through the interaction between octyl groups and organic solvents. The structure, morphology, dry density, porosity and equilibrium water content of porous octyl-dextran microspheres were systematically investigated. The octyl content affected the properties of microspheres. The results showed that the dry density of microspheres decreased from 2.35 to 1.21 g/ml, porosity increased from 80.68 to 95.05% with the octyl content increasing from 0.49 to 2.28 mmol/g. Meanwhile, the equilibrium water content presented a peak value (90.18%) when the octyl content was 2.25 mmol/g. Octyl-dextran microspheres showed high capacity. Naturally drug carriers play an important role in drug-delivery systems for their biodegradability, wide raw materials sources and nontoxicity. Doxorubicin (DOX) was used as a drug model to examine the drug-loading capacity of porous octyl-dextran microspheres. The drug-loading efficiency increased with the increase in microspheres/drug ratio, while the encapsulation efficiency decreased. When microspheres/drug mass ratio was 4/1, the drug-loading efficiency and encapsulation efficiency were 10.20 and 51.00%, respectively. The release rate of DOX increased as drug content and porosity increased. In conclusion, porous octyl-dextran microspheres were synthesized successfully and have the potential to serve as an effective delivery system in drug controlled release.

New Method to Prepare Mitomycin C Loaded PLA-Nanoparticles with High Drug Entrapment Efficiency

NASA Astrophysics Data System (ADS)

Hou, Zhenqing; Wei, Heng; Wang, Qian; Sun, Qian; Zhou, Chunxiao; Zhan, Chuanming; Tang, Xiaolong; Zhang, Qiqing

2009-07-01

The classical utilized double emulsion solvent diffusion technique for encapsulating water soluble Mitomycin C (MMC) in PLA nanoparticles suffers from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. In this paper, MMC loaded PLA nanoparticles were prepared by a new single emulsion solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of MMC by formation of MMC-SPC complex. Four main influential factors based on the results of a single-factor test, namely, PLA molecular weight, ratio of PLA to SPC (wt/wt) and MMC to SPC (wt/wt), volume ratio of oil phase to water phase, were evaluated using an orthogonal design with respect to drug entrapment efficiency. The drug release study was performed in pH 7.2 PBS at 37 °C with drug analysis using UV/vis spectrometer at 365 nm. MMC-PLA particles prepared by classical method were used as comparison. The formulated MMC-SPC-PLA nanoparticles under optimized condition are found to be relatively uniform in size (594 nm) with up to 94.8% of drug entrapment efficiency compared to 6.44 μm of PLA-MMC microparticles with 34.5% of drug entrapment efficiency. The release of MMC shows biphasic with an initial burst effect, followed by a cumulated drug release over 30 days is 50.17% for PLA-MMC-SPC nanoparticles, and 74.1% for PLA-MMC particles. The IR analysis of MMC-SPC complex shows that their high liposolubility may be attributed to some weak physical interaction between MMC and SPC during the formation of the complex. It is concluded that the new method is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and longer sustained drug release in comparison to classical method.

Aerosolized Antimicrobial Agents Based on Degradable Dextran Nanoparticles Loaded with Silver Carbene Complexes

PubMed Central

Ornelas-Megiatto, Cátia; Shah, Parth N.; Wich, Peter R.; Cohen, Jessica L.; Tagaev, Jasur A.; Smolen, Justin A.; Wright, Brian D.; Panzner, Matthew J.; Youngs, Wiley J.; Fréchet, Jean M. J.; Cannon, Carolyn L.

2012-01-01

Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH2Cl2 (organic): PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery. PMID:23025592

Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes.

PubMed

Ornelas-Megiatto, Cátia; Shah, Parth N; Wich, Peter R; Cohen, Jessica L; Tagaev, Jasur A; Smolen, Justin A; Wright, Brian D; Panzner, Matthew J; Youngs, Wiley J; Fréchet, Jean M J; Cannon, Carolyn L

2012-11-05

Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH(2)Cl(2) (organic):PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery.

Enhancing the Solubility and Oral Bioavailability of Poorly Water-Soluble Drugs Using Monoolein Cubosomes.

PubMed

Ali, Md Ashraf; Kataoka, Noriko; Ranneh, Abdul-Hackam; Iwao, Yasunori; Noguchi, Shuji; Oka, Toshihiko; Itai, Shigeru

2017-01-01

Monoolein cubosomes containing either spironolactone (SPI) or nifedipine (NI) were prepared using a high-pressure homogenization technique and characterized in terms of their solubility and oral bioavailability. The mean particle size, polydispersity index (PDI), zeta potential, solubility and encapsulation efficiency (EE) values of the SPI- and NI-loaded cubosomes were determined to be 90.4 nm, 0.187, -13.4 mV, 163 µg/mL and 90.2%, and 91.3 nm, 0.168, -12.8 mV, 189 µg/mL and 93.0%, respectively, which were almost identical to those of the blank cubosome. Small-angle X-ray scattering analyses confirmed that the SPI-loaded, NI-loaded and blank cubosomes existed in the cubic space group Im3̄m. The lattice parameters of the SPI- and NI-loaded cubosomes were 147.6 and 151.6 Å, respectively, making them almost identical to that of blank cubosome (151.0 Å). The in vitro release profiles of the SPI- and NI-loaded cubosomes showed that they released less than 5% of the drugs into various media over 12-48 h, indicating that most of the drug remained encapsulated within the cubic phase of their lipid bilayer. Furthermore, the in vivo pharmacokinetic results suggested that these cubosomes led to a considerable increase in the systemic oral bioavailability of the drugs compared with pure dispersions of the same materials. Notably, the stability results indicated that the mean particle size and PDI values of these cubosomes were stable for at least 4 weeks. Taken together, these results demonstrate that monoolein cubosomes represent promising drug carriers for enhancing the solubility and oral bioavailability of poorly water-soluble drugs.

PET/NIRF/MRI triple functional iron oxide nanoparticles.

PubMed

Xie, Jin; Chen, Kai; Huang, Jing; Lee, Seulki; Wang, Jinhua; Gao, Jinhao; Li, Xingguo; Chen, Xiaoyuan

2010-04-01

Engineered nanoparticles with theranostic functions have attracted a lot of attention for their potential role in the dawning era of personalized medicine. Iron oxide nanoparticles (IONPs), with their advantages of being non-toxic, biodegradable and inexpensive, are candidate platforms for the buildup of theranostic nanostructures; however, progress in using them has been limited largely due to inefficient drug loading and delivery. In the current study, we utilized dopamine to modify the surface of IONPs, yielding nanoconjugates that can be easily encapsulated into human serum albumin (HSA) matrices (clinically utilized drug carriers). This nanosystem is well-suited for dual encapsulation of IONPs and drug molecules, because the encapsulation is achieved in a way that is similar to common drug loading. To assess the biophysical characteristics of this novel nanosystem, the HSA coated IONPs (HSA-IONPs) were dually labeled with (64)Cu-DOTA and Cy5.5, and tested in a subcutaneous U87MG xenograft mouse model. In vivo positron emission tomography (PET)/near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) tri-modality imaging, and ex vivo analyses and histological examinations were carefully conducted to investigate the in vivo behavior of the nanostructures. With the compact HSA coating, the HSA-IONPs manifested a prolonged circulation half-life; more impressively, they showed massive accumulation in lesions, high extravasation rate, and low uptake of the particles by macrophages at the tumor area. Published by Elsevier Ltd.

Controllable delivery of hydrophilic and hydrophobic drugs from electrospun poly(lactic-co-glycolic acid)/mesoporous silica nanoparticles composite mats.

PubMed

Song, Botao; Wu, Chengtie; Chang, Jiang

2012-11-01

Co-delivery of several drugs has been regarded as an alternative strategy for achieving enhanced therapeutic effect. In this study, a co-delivery system based on the electrospun poly(lactic-co-glycolic acid) (PLGA)/mesoporous silica nanoparticles (MSNs) composite mat was designed for the co-encapsulation and prolonged release of one hydrophilic and one hydrophobic drug simultaneously. MSNs were chosen to load the hydrophobic model drug fluorescein (FLU) and hydrophilic model drug rhodamine B (RHB), respectively (named as RHB-loaded MSNs and FLU-loaded MSNs). Two kinds of drug-loaded MSNs were incorporated into the polymer matrix to form a fibrous structure by blending electrospinning. The effect of the weight ratios for the two kinds of drug-loaded MSNs and the initial PLGA concentrations on the drug release kinetics were systematically investigated. The results showed that both model drugs RHB and FLU maintained sustained delivery with controllable release kinetics during the releasing period, and the release kinetics was closely dependent on the loading ratios of two drug-loaded MSNs and the initial PLGA concentrations in the composite mats. The results suggest that the co-drug delivery system may be used for wound dressing that requires the combined therapy of several kinds of drugs. Copyright © 2012 Wiley Periodicals, Inc.

Formulation, characterization and pharmacokinetics of praziquantel-loaded hydrogenated castor oil solid lipid nanoparticles.

PubMed

Xie, Shuyu; Pan, Baoliang; Wang, Ming; Zhu, Luyan; Wang, Fenghua; Dong, Zhao; Wang, Xiaofang; Zhou, WenZhong

2010-07-01

The purpose of this study was to formulate praziquantel (PZQ)-loaded hydrogenated castor oil (HCO) solid lipid nanoparticles (SLN) to enhance the bioavailability and prolong the systemic circulation of the drug. PZQ was encapsulated into HCO nanoparticles by a hot homogenization and ultrasonication method. The physicochemical characteristics of SLN were investigated by optical microscope, scanning electron microscopy and photon correlation spectroscopy. Pharmacokinetics were studied after oral, subcutaneous and intramuscular administration in mice. The diameter, polydispersivity index, zeta potential, encapsulation efficiency and loading capacity of the nanoparticles were 344.0 +/- 15.1 nm, 0.31 +/- 0.08, -16.7 +/- 0.5 mV, 62.17 +/- 6.53% and 12.43 +/- 1.31%, respectively. In vitro release of PZQ-loaded HCO-SLN exhibited an initial burst release followed by a sustained release. SLN increased the bioavailability of PZQ by 14.9-, 16.1- and 2.6-fold, and extended the mean residence time of the drug from 7.6, 6.6 and 8.2 to 95.9, 151.6 and 48.2 h after oral, subcutaneous and intramuscular administration, respectively. The PZQ-loaded HCO-SLN could be a promising formulation to enhance the pharmacological activity of PZQ.

Preparation and in vitro characterization of SN-38-loaded, self-forming polymeric depots as an injectable drug delivery system.

PubMed

Manaspon, Chawan; Hongeng, Suradej; Boongird, Atthaporn; Nasongkla, Norased

2012-10-01

This work describes the preparation and characterization of anticancer-loaded injectable polymeric depots that consisted of D,L-lactide (LA), ε-caprolactone (CL), and poly(ethylene glycol) (PEG) or [poly(ε-caprolactone)-random-poly(D,L-lactide)]-block-poly(ethylene glycol)-block-[poly(ε-caprolactone)-random-poly(D,L-lactide)] (PLEC) copolymers for malignant gliomas treatment. PLECs were polymerized with different percentages of LA to deliver 7-ethyl-10-hydroxycamptothecin (SN-38), a highly potent anticancer drug. SN-38-loaded depots could form directly in phosphate buffer saline with more than 98% encapsulation efficiency. The release rate of SN-38 from depots was found to depend on the amount of LA in PLECs, loading content of SN-38 in the depots, and depot weight. Encapsulation of SN-38 inside depots could enhance the stability of SN-38 where all of SN-38 released after 60 days was in an active form. Depots without SN-38 were evaluated as noncytotoxic against U-87MG, whereas SN-38-loaded depots showed cytotoxic effect as a function of concentration. Copyright © 2012 Wiley Periodicals, Inc.

PEG-coumarin nanoaggregates as π-π stacking derived small molecule lipophile containing self-assemblies for anti-tumour drug delivery.

PubMed

Behl, Gautam; Kumar, Parveen; Sikka, Manisha; Fitzhenry, Laurence; Chhikara, Aruna

2018-03-01

Polymeric self-assemblies formed by non-covalent interactions such as hydrophobic interactions, hydrogen bonding, π-π stacking, host-guest and electrostatic interactions have been utilised widely and exhibit controlled release of encapsulated drug. Beside carrier-carrier interactions, small molecule amphiphiles exhibiting carrier-drug interactions have recently been an area of interest for cancer drug delivery, as most of the hydrophobic anti-tumour drugs are aromatic and exhibit π-π conjugated structure. In the present study PEG-coumarin (PC) conjugates forming self-assembled nanoaggregates were synthesised with PEG (polyethylene glycol) as hydrophilic block and coumarin as small molecule lipophilic segment. Curcumin (CUR) as model conjugated aromatic drug was loaded in to the nanoaggregates via dual hydrophobic and π-π stacking interactions. The interactions between the conjugates and CUR, drug release profile and in vitro anti-tumour efficacy were investigated in detail. CUR-loaded nanoaggregate self-assembly was driven by π-π interactions and a maximum loading level of about 18 wt.% (~60 % encapsulation efficiency) was achieved. The average hydrodynamic diameter (D av ) was in the range of 120-160 nm and a spherical morphology was observed by transmission electron microscopy (TEM). A sustained release of CUR was observed for 90 h. Cytotoxicity evaluation of CUR-loaded nanoaggregates on pancreatic cancer cell lines indicated higher efficacy, IC 50 ~11 and ~15 μM as compared to free CUR, IC 50 ~14 and ~20 μM on human pancreatic carcinoma (MIA PaCa-2) and human pancreatic duct epithelioid carcinoma (PANC-1) cell lines respectively. PC conjugates provided a new strategy of fabricating nanoparticles for drug delivery and may form the basis for the development of advanced biomaterials in near future.

Preparation and Evaluation of Multiple Nanoemulsions Containing Gadolinium (III) Chelate as a Potential Magnetic Resonance Imaging (MRI) Contrast Agent.

PubMed

Sigward, Estelle; Corvis, Yohann; Doan, Bich-Thuy; Kindsiko, Kadri; Seguin, Johanne; Scherman, Daniel; Brossard, Denis; Mignet, Nathalie; Espeau, Philippe; Crauste-Manciet, Sylvie

2015-09-01

The objective was to develop, characterize and assess the potentiality of W1/O/W2 self-emulsifying multiple nanoemulsions to enhance signal/noise ratio for Magnetic Resonance Imaging (MRI). For this purpose, a new formulation, was designed for encapsulation efficiency and stability. Various methods were used to characterize encapsulation efficiency ,in particular calorimetric methods (Differential Scanning Calorimetry (DSC), thermogravimetry analysis) and ultrafiltration. MRI in vitro relaxivities were assessed on loaded DTPA-Gd multiple nanoemulsions. Characterization of the formulation, in particular of encapsulation efficiency was a challenge due to interactions found with ultrafiltration method. Thanks to the specifically developed DSC protocol, we were able to confirm the formation of multiple nanoemulsions, differentiate loaded from unloaded nanoemulsions and measure the encapsulation efficiency which was found to be quite high with a 68% of drug loaded. Relaxivity studies showed that the self-emulsifying W/O/W nanoemulsions were positive contrast agents, exhibiting higher relaxivities than those of the DTPA-Gd solution taken as a reference. New self-emulsifying multiple nanoemulsions that were able to load satisfactory amounts of contrasting agent were successfully developed as potential MRI contrasting agents. A specific DSC protocol was needed to be developed to characterize these complex systems as it would be useful to develop these self-formation formulations.

Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems.

PubMed

Jelezova, Ivelina; Drakalska, Elena; Momekova, Denitsa; Shalimova, Natalia; Momekov, Georgi; Konstantinov, Spiro; Rangelov, Stanislav; Pispas, Stergios

2015-10-12

Curcumin is a perspective drug candidate with pleiotropic antineoplastic activity, whose exceptionally low aqueous solubility and poor pharmacokinetic properties have hampered its development beyond the preclinical level. A possible approach to overcome these limitations is the encapsulation of curcumin into nano-carriers, incl. liposomes. The present contribution is focused on feasibility of using hybrid pH-sensitive liposomes, whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with PEGylated tert-butylcalix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. The inclusion complexes were encapsulated in dipalmithoylphosphathydilcholine:cholesterol liposomes, whose membranes were grafted with a poly(isoprene-b-acrylic acid) diblock copolymer to confer pH-sensitivity. The liposomes were characterized by DLS, ζ-potential measurements, cryo-TEM, curcumin encapsulation efficacy, loading capacity, and in vitro release as a function of pH. Free and formulated curcumin were further investigated for cytotoxicity, apoptosis-induction and caspase-8, and 9 activation in chemosensitive HL-60 and its resistant sublines HL-60/Dox and HL-60/CDDP. Formulated curcumin was superior cytotoxic and apoptogenic agent vs. the free drug. The mechanistic assay demonstrated that the potent proapoptotic effects of pH-sensitive liposomal curcumin presumably mediated via recruitment of both extrinsic and intrinsic apoptotic pathways in both HL-60 and HL-60/CDDP cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of biodegradable drug delivery system to treat addiction.

PubMed

Mandal, T K

1999-06-01

Opiate addiction is a serious problem that has now spread worldwide to all levels of society. Buprenorphine has been used for several years for the treatment of opiate addiction. The objective of this project was to develop sustained-release biodegradable microcapsules for the parenteral delivery of buprenorphine. Biodegradable microcapsules of buprenorphine/poly(lactide-co-glycolide) were prepared using two main procedures based on an in-water drying process in a complex emulsion system. These procedures differ in the way the organic solvent was eliminated: evaporation or extraction. The effect of drug loading and the effect of partial saturation of the aqueous phase with the core material during the in-water solvent evaporation were also studied. The efficiency of encapsulation increased from 11% to 34% when the drug loading was decreased from 20% to 5%. There was no significant change in the efficiency of encapsulation when the aqueous phase was partially saturated with buprenorphine. In changing the solvent removal process from evaporation to extraction, no significant change in the efficiency of encapsulation was observed. The microcapsules prepared by the solvent evaporation were smooth and spherical. However, the microcapsules prepared by the extraction of the organic solvent lost their surface smoothness and became slightly irregular and porous compared with the other batches. The average particle size of the microcapsules was between 14 and 49 microns. The cumulative drug release was between 2% and 4% within the first 24 hr. A sustained drug release continued over 45 days.

Polydopamine-functionalized nanographene oxide: a versatile nanocarrier for chemotherapy and photothermal therapy

NASA Astrophysics Data System (ADS)

Zhang, Xinyuan; Nan, Xu; Shi, Wei; Sun, Yanan; Su, Huiling; He, Yuan; Liu, Xin; Zhang, Zhong; Ge, Dongtao

2017-07-01

For releasing both drug and heat to selected sites, a combination of chemotherapy and photothermal therapy in one system is a more effective way to destroy cancer cells than monotherapy. Graphene oxide (GO) with high drug-loading efficiency and near-infrared (NIR) absorbance has great potential in drug delivery and photothermal therapy, but it is difficult to load drugs with high solubility. Herein, we develop a versatile drug delivery nanoplatform based on GO for integrated chemotherapy and photothermal therapy by a facile method of simultaneous reduction and surface functionalization of GO with poly(dopamine) (PDA). Due to the excellent adhesion of PDA, both low and high solubility drugs can be encapsulated in the PDA-functionalized GO nanocomposite (rGO-PDA). The fabricated nanocomposite exhibits good biocompatibility, excellent photothermal performance, high drug loading capacity, an outstanding sustained release property, and efficient endocytosis. Moreover, NIR laser irradiation facilitates the release of loaded drugs from rGO-PDA. These features make the rGO-PDA nanocomposite achieve excellent in vivo synergistic antitumor therapeutic efficacy.

Development of Metronidazole-Loaded Colon-Targeted Microparticulate Drug Delivery System.

PubMed

Kumar, Manoj; Awasthi, Rajendra

2015-01-01

Crohn’s disease and ulcerative colitis are the main autoimmune inflammatory bowel diseases. Metronidazole is the most commonly used drug for the treatment of Crohn’s disease. However, the pharmacokinetic profile of this drug indicates that the largest amount of the drug is absorbed from the upper part of the intestines and very little concentration of the drugs reaches the colon.Objectives: The aim of this investigation was to formulate metronidazole loaded microspheres for the efficient therapy of inflammatory bowel diseases.Material and Methods: Microspheres were prepared using the emulsification-solvent evaporation method. The effect of Eudragit S100 concentration and the ratio of liquid paraffin (light: heavy) on percentage yield, particle size, morphology, drug encapsulation and in vitro drug release was examined. Drug-polymer interaction was investigated using Fourier Transformed Infrared Spectroscopy (FTIR). The results showed that the particle had good flow properties, encapsulation efficiency (56.11 ・} 1.51–81.02 ・} 2.14%)and cumulative drug release (64.14 ・} 0.83–79.69 ・} 2.45%) in a phosphate buffer (pH 6.8) after 10 h of the dissolution study.An increased particle size was observed with an increasing polymer concentration. It was observed that the Eudragit had a positive effect on the drug encapsulation and negative effect on drug release. Aggregation of drug-polymer droplets was observed at a lower level of magnesium stearate during microsphere preparation. The results of FTIR spectroscopy revealed the absence of any drug-polymer interactions. However, slight peak shifting and suppression in peak height was observed.This might be due to the minor ionic interactions. The microspheres were discrete, spherical and free-flowing. The spherical shape of the microspheres was confirmed from SEM photomicrographs. The developed microspheres showed a controlled drug release and were found to follow Higuchi’s model. The release mechanism of metronidazole from the microspheres was Fickian diffusion without swelling. The results suggest that the developed microspheres could enhance drug entrapment, and inflect the drug release.

Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier

PubMed Central

Tian, Shuangyan; Li, Juan; Tao, Qi; Zhao, Yawen; Lv, Zhufen; Yang, Fan; Duan, Haoyun; Chen, Yanzhong; Zhou, Qingjun; Hou, Dongzhi

2018-01-01

Background Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. Materials and methods To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion–solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. Results Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. Conclusion The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma. PMID:29391798

Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier.

PubMed

Tian, Shuangyan; Li, Juan; Tao, Qi; Zhao, Yawen; Lv, Zhufen; Yang, Fan; Duan, Haoyun; Chen, Yanzhong; Zhou, Qingjun; Hou, Dongzhi

2018-01-01

Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion-solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma.

[Fabrication of a new composite scaffold material for delivering rifampicin and its sustained drug release in rats].

PubMed

Ma, Xue-Ming; Lin, Zhen; Zhang, Jia-Wei; Sang, Chao-Hui; Qu, Dong-Bin; Jiang, Jian-Ming

2016-03-01

To fabricate a new composite scaffold material as an implant for sustained delivery of rifampicin and evaluate its performance of sustained drug release and biocompatibility. The composite scaffold material was prepared by loading poly(lactic-co-glycolic) acid (PLGA) microspheres that encapsulated rifampicin in a biphasic calcium composite material with a negative surface charge. The in vitro drug release characteristics of the microspheres and the composite scaffold material were evaluated; the in vivo drug release profile of the composite scaffold material implanted in a rat muscle pouch was evaluated using high-performance liquid chromatography. The biochemical parameters of the serum and liver histopathologies of the rats receiving the transplantation were observed to assess the biocompatibility of the composite scaffold material. The encapsulation efficiency and drug loading efficiency of microspheres were (56.05±5.33)% and (29.80±2.88)%, respectively. The cumulative drug release rate of the microspheres in vitro was (94.19±5.4)% at 28 days, as compared with the rate of (82.23±6.28)% of composite scaffold material. The drug-loaded composite scaffold material showed a good performance of in vivo drug release in rats, and the local drug concentration still reached 16.18±0.35 µg/g at 28 days after implantation. Implantation of the composite scaffold material resulted in transient and reversible liver injury, which was fully reparred at 28 days after the implantation. The composite scaffold material possesses a good sustained drug release capacity and a good biocompatibility, and can serve as an alternative approach to conventional antituberculous chemotherapy.

Targeting doxorubicin encapsulated in stealth liposomes to solid tumors by non thermal diode laser.

PubMed

Ghannam, Magdy M; El Gebaly, Reem; Fadel, Maha

2016-04-05

The use of liposomes as drug delivery systems is the most promising technique for targeting drug especially for anticancer therapy. In this study sterically stabilized liposomes was prepared from DPPC/Cholesterol/PEG-PE encapsulated doxorubicin. The effect of lyophilization on liposomal stability and hence expiration date were studied. Moreover, the effect of diode laser on the drug released from liposomesin vitro and in vivo in mice carrying implanted solid tumor were also studied. The results indicated that lyophilization of the prepared liposomes encapsulating doxorubicin led to marked stability when stored at 5 °C and it is possible to use the re-hydrated lyophilized liposomes within 12 days post reconstitution. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells is a promising method in cancer therapy. We can conclude that lyophilization of the liposomes encapsulating doxorubicin lead to marked stability for the liposomes when stored at 5 °C. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells through the use of photosensitive sterically stabilized liposomes loaded with doxorubicin is a promising method. It proved to be applicable and successful for treatment of Ehrlich solid tumors implanted in mice and eliminated toxic side effects of doxorubicin.

Electrospray of multifunctional microparticles for image-guided drug delivery

NASA Astrophysics Data System (ADS)

Zhang, Leilei; Yan, Yan; Mena, Joshua; Sun, Jingjing; Letson, Alan; Roberts, Cynthia; Zhou, Chuanqing; Chai, Xinyu; Ren, Qiushi; Xu, Ronald

2012-03-01

Anti-VEGF therapies have been widely explored for the management of posterior ocular disease, like neovascular age-related macular degeneration (AMD). Loading anti-VEGF therapies in biodegradable microparticles may enable sustained drug release and improved therapeutic outcome. However, existing microfabrication processes such as double emulsification produce drug-loaded microparticles with low encapsulation rate and poor antibody bioactivity. To overcome these limitations, we fabricate multifunctional microparticles by both single needle and coaxial needle electrospray. The experimental setup for the process includes flat-end syringe needles (both single needle and coaxial needle), high voltage power supplies, and syringe pumps. Microparticles are formed by an electrical field between the needles and the ground electrode. Droplet size and morphology are controlled by multiple process parameters and material properties, such as flow rate and applied voltage. The droplets are collected and freezing dried to obtain multifunctional microparticles. Fluorescent beads encapsulated poly(DL-lactide-co-glycolide) acid (PLGA) microparticles are injected into rabbits eyes through intravitreal injection to test the biodegradable time of microparticles.

Nanoscale coordination polymers for anticancer drug delivery

NASA Astrophysics Data System (ADS)

Phillips, Rachel Huxford

This dissertation reports the synthesis and characterization of nanoscale coordination polymers (NCPs) for anticancer drug delivery. Nanoparticles have been explored in order to address the limitations of small molecule chemotherapeutics. NCPs have been investigated as drug delivery vehicles as they can exhibit the same beneficial properties as the bulk metal-organic frameworks as well as interesting characteristics that are unique to nanomaterials. Gd-MTX (MTX = methotrexate) NCPs with a MTX loading of 71.6 wt% were synthesized and stabilized by encapsulation within a lipid bilayer containing anisamide (AA), a small molecule that targets sigma receptors which are overexpressed in many cancer tissues. Functionalization with AA allows for targeted delivery and controlled release to cancer cells, as shown by enhanced efficacy against leukemia cells. The NCPs were doped with Ru(bpy)32+ (bpy = 2,2'-bipyridine), and this formulation was utilized as an optical imaging agent by confocal microscopy. NCPs containing the chemotherapeutic pemetrexed (PMX) were synthesized using different binding metals. Zr-based materials could not be stabilized by encapsulation with a lipid bilayer, and Gd-based materials showed that PMX had degraded during synthesis. However, Hf-based NCPs containing 19.7 wt% PMX were stabilized by a lipid coating and showed in vitro efficacy against non-small cell lung cancer (NSCLC) cell lines. Enhanced efficacy was observed for formulations containing AA. Additionally, NCP formulations containing the cisplatin prodrug disuccinatocisplatin were prepared; one of these formulations could be stabilized by encapsulation within a lipid layer. Coating with a lipid layer doped with AA rendered this formulation an active targeting agent. The resulting formulation proved more potent than free cisplatin in NSCLC cell lines. Improved NCP uptake was demonstrated by confocal microscopy and competitive binding assays. Finally, a Pt(IV) oxaliplatin prodrug was synthesized and incorporated in different NCPs using various binding metals. A moderate drug loading of 44.9 wt% was determined for Zr-based NCPs. This drug loading, along with a diameter less than 200 nm, make these particles promising candidates for further stabilization via lipid encapsulation.

PLGA nanoparticles introduction into mitoxantrone-loaded ultrasound-responsive liposomes: In vitro and in vivo investigations.

PubMed

Xin, Yuxuan; Qi, Qi; Mao, Zhenmin; Zhan, Xiaoping

2017-08-07

A novel ultrasound-responsive liposomal system for tumor targeting was prepared in order to increase the antitumor efficacy and decrease serious side effects. In this paper, PLGA nanoparticles were used ultrasound-responsive agents instead of conventional microbubbles. The PLGA-nanoparticles were prepared by an emulsion solvent evaporation method. The liposomes were prepared by a lipid film hydration method. Particle size, zeta potential, encapsulation efficiency and drug loading capacity of the liposomes were studied by light scattering analysis and dialysis. Transmission electron microscopy (TEM) and atomic force microscope (AFM) were used to investigate the morphology of liposomes. The release in vitro was carried out in the pH 7.4 phosphate buffer solutions, as a result, liposome L3 encapsulating PLGA-nanoparticles displayed good stability under simulative physiological conditions and quickly responsive release under the ultrasound. The release in vivo was carried out on the rats, as a result, liposome L3 showed higher bioavailability than traditional intravenous injectable administration, and liposome L3 showed higher elimination ratio after stimulation by ultrasound than L3 without stimulation. Thus, the novel ultrasound-responsive liposome encapsulating PLGA-nanoparticles has a potential to be developed as a new drug delivery system for anti-tumor drug. Copyright © 2017 Elsevier B.V. All rights reserved.

Large-scale preparation of clove essential oil and eugenol-loaded liposomes using a membrane contactor and a pilot plant.

PubMed

Sebaaly, Carine; Greige-Gerges, Hélène; Agusti, Géraldine; Fessi, Hatem; Charcosset, Catherine

2016-01-01

Based on our previous study where optimal conditions were defined to encapsulate clove essential oil (CEO) into liposomes at laboratory scale, we scaled-up the preparation of CEO and eugenol (Eug)-loaded liposomes using a membrane contactor (600 mL) and a pilot plant (3 L) based on the principle of ethanol injection method, both equipped with a Shirasu Porous Glass membrane for injection of the organic phase into the aqueous phase. Homogenous, stable, nanometric-sized and multilamellar liposomes with high phospholipid, Eug loading rates and encapsulation efficiency of CEO components were obtained. Saturation of phospholipids and drug concentration in the organic phase may control the liposome stability. Liposomes loaded with other hydrophobic volatile compounds could be prepared at large scale using the ethanol injection method and a membrane for injection.

Microfabrication of curcumin-loaded microparticles using coaxial electrohydrodynamic atomization

NASA Astrophysics Data System (ADS)

Yuan, Shuai; Si, Ting; Liu, Zhongfa; Xu, Ronald X.

2014-03-01

Encapsulation of curcumin in PLGA microparticles is performed by a coaxial electrohydrodynamic atomization device. To optimize the process, the effects of different control parameters on morphology and size distribution of resultant microparticles are studied systemically. Four main flow modes are identified as the applied electric field intensity increases. The stable cone-jet configuration is found to be available for fabricating monodisperse microparticles with core-shell structures. The results are compared with those observed in traditional emulsion. The drug-loading efficiency is also checked. The present system is advantageous for the enhancement of particle size distribution and drug-loading efficiency in various applications such as drug delivery, biomedicine and image-guided therapy.

Poly(L-lactide)/halloysite nanotube electrospun mats as dual-drug delivery systems and their therapeutic efficacy in infected full-thickness burns.

PubMed

Zhang, Xiazhi; Guo, Rui; Xu, Jiqing; Lan, Yong; Jiao, Yanpeng; Zhou, Changren; Zhao, Yaowu

2015-11-01

In this study, poly(L-lactide) (PLLA)/halloysite nanotube (HNT) electrospun mats were prepared as a dual-drug delivery system. HNTs were used to encapsulate polymyxin B sulphate (a hydrophilic drug). Dexamethasone (a hydrophobic drug) was directly dissolved in the PLLA solution. The drug-loaded HNTs with optimised encapsulation efficiency were then mixed with the PLLA solution for subsequent electrospinning to form composite dual-drug-loaded fibre mats. The structure, morphology, degradability and mechanical properties of the electrospun composite mats were characterised in detail. The results showed that the HNTs were uniformly distributed in the composite PLLA mats. The HNTs content in the mats could change the morphology and average diameter of the electrospun fibres. The HNTs improved both the tensile strength of the PLLA electrospun mats and their degradation ratio. The drug-release kinetics of the electrospun mats were investigated using ultraviolet-visible spectrophotometry. The HNTs/PLLA ratio could be varied to adjust the release of polymyxin B sulphate and dexamethasone. The antibacterial activity in vitro of the mats was evaluated using agar diffusion and turbidimetry tests, which indicated the antibacterial efficacy of the dual-drug delivery system against Gram-positive and -negative bacteria. Healing in vivo of infected full-thickness burns and infected wounds was investigated by macroscopic observation, histological observation and immunohistochemical staining. The results indicated that the electrospun mats were capable of co-loading and co-delivering hydrophilic and hydrophobic drugs, and could potentially be used as novel antibacterial wound dressings. © The Author(s) 2015.

Flash NanoPrecipitation (FNP) for bioengineering nanoparticles to enhance the bioavailability

NASA Astrophysics Data System (ADS)

Feng, Jie; Zhang, Yingyue; McManus, Simone; Prud'Homme, Robert

2017-11-01

Nanoparticles for the delivery of therapeutics have been one of the successful areas in biomedical nanotechnology. Nanoparticles improve bioavailability by 1) the higher surface-to-volume ratios, enhancing dissolution rates, and 2) trapping drug molecules in higher energy, amorphous states for a higher solubility. However, conventional direct precipitation to prepare nanoparticles has the issues of low loading and encapsulation efficiency. Here we demonstrate a kinetically controlled and rapid-precipitation process called Flash NanoPrecipitation (FNP), to offer a multi-phase mixing platform for bioengineering nanoparticles. With the designed geometry in the micro-mixer, we can generate nanoparticles with a narrow size distribution, while maintaining high loading and encapsulation efficiency. By controlling the time scales in FNP, we can tune the nanoparticle size and the robustness of the process. Remarkably, the dissolution rates of the nanoparticles are significantly improved compared with crystalline drug powders. Furthermore, we investigate how to recover the drug-loaded nanoparticles from the aqueous dispersions. Regarding the maintenance of the bioavailability, we discuss the advantages and disadvantages of each drying process. These results suggest that FNP offers a versatile and scalable nano-fabrication platform for biomedical engineering.

Antibiotic release from biodegradable PHBV microparticles.

PubMed

Sendil, D; Gürsel, I; Wise, D L; Hasirci, V

1999-05-20

For the treatment of periodontal diseases, design of a controlled release system seemed very appropriate for an effective, long term result. In this study a novel, biodegradable microbial polyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PHBV of various valerate contents containing a well established antibiotic, tetracycline, known to be effective against many of the periodontal disease related microorganisms, was used in the construction of a controlled release system. Tetracycline was loaded in the PHBV microspheres and microcapsules both in its acidic (TC) and in neutral form (TCN). Microcapsules of PHBV were prepared under different conditions using w/o/w double emulsion and their properties such as encapsulation efficiency, loading, release characteristics, and morphological properties were investigated. It was found that concentration of emulsifiers polyvinyl alcohol (PVA) and gelatin (varied between 0-4%) influenced the encapsulation efficiency appreciably. In order to increase encapsulation efficiency (from the obtained range of 18.1-30.1%) and slow down the release of the highly soluble tetracycline.HCl, it was neutralized with NaOH. Encapsulation efficiency of neutralized tetracycline was much higher (51.9-65.3%) due to the insoluble form of the drug used during encapsulation. The release behaviour of neither of the drugs was found to be of zero order. Rather the trends fitted reasonably well to Higuchi's approach for release from spherical micropheres. Biodegradability was not an appreciable parameter in the release from microcapsules because release was complete before any signs of degradation were observed.

Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles.

PubMed

Gupta, Biki; Poudel, Bijay Kumar; Pathak, Shiva; Tak, Jin Wook; Lee, Hee Hyun; Jeong, Jee-Heon; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2016-06-01

Imatinib (IMT), an anticancer agent, inhibits receptor tyrosine kinases and is characterized by poor aqueous solubility, extensive first-pass metabolism, and rapid clearance. The aims of the current study are to prepare imatinib-loaded solid lipid nanoparticles (IMT-SLN) and study the effects of associated formulation variables on particle size and drug encapsulation on IMT-SLN using an experimental design. IMT-SLN was optimized by use of a "combo" approach involving Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD screening resulted in the determination of organic-to-aqueous phase ratio (O/A), drug-to-lipid ratio (D/L), and amount of Tween® 20 (Tw20) as three significant variables for particle size (S z), drug loading (DL), and encapsulation efficiency (EE) of IMT-SLN, which were used for optimization by BBD, yielding an optimized criteria of O/A = 0.04, D/L = 0.03, and Tw20 = 2.50% w/v. The optimized IMT-SLN exhibited monodispersed particles with a size range of 69.0 ± 0.9 nm, ζ-potential of -24.2 ± 1.2 mV, and DL and EE of 2.9 ± 0.1 and 97.6 ± 0.1% w/w, respectively. Results of in vitro release study showed a sustained release pattern, presumably by diffusion and erosion, with a higher release rate at pH 5.0, compared to pH 7.4. In conclusion, use of the combo experimental design approach enabled clear understanding of the effects of various formulation variables on IMT-SLN and aided in the preparation of a system which exhibited desirable physicochemical and release characteristics.

Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer.

PubMed

Zhang, Bo; Song, Yunmei; Wang, Tianqi; Yang, Shaomei; Zhang, Jing; Liu, Yongjun; Zhang, Na; Garg, Sanjay

2017-01-01

Combinational nanomedicine is becoming a topic of much interest in cancer therapy, although its translation into the clinic remains extremely challenging. One of the main obstacles lies in the difficulty to efficiently co-deliver immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co-delivery abilities between co-loaded LEs and mixture formulation. Multiple oxaliplatin/irinotecan drug-phospholipid complexes (DPCs) were formulated. Co-loaded LEs were prepared using DPC technique to efficiently encapsulate both drugs. Co-loaded LEs exhibited uniform particle size distribution, desired stability and synchronous release profiles in both drugs. Co-loaded LEs demonstrated superior anti-tumor activity compared with the simple solution mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers could co-deliver both drugs into the same cells more efficiently and exhibited the optimized synergistic effect. These results indicate that co-loaded LEs could be a desired formulation for enhanced cancer therapy with potential application prospects. The comparison between co-loaded LEs and mixture formulation is significant for pharmaceutical designs aimed at co-delivery of multiple drugs.

Evaluation of self-assembled HCPT-loaded PEG-b-PLA nanoparticles by comparing with HCPT-loaded PLA nanoparticles.

PubMed

Yang, Xiangrui; Wu, Shichao; Wang, Yange; Li, Yang; Chang, Di; Luo, Yin; Ye, Shefang; Hou, Zhenqing

2014-12-01

We present a dialysis technique to prepare the 10-hydroxycamptothecin (HCPT)-loaded nanoparticles (NPs) using methoxypolyethylene glycol-poly(D,L-lactide) (PEG-b-PLA) and PLA, respectively. Both HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs were characterized by differential scanning calorimetry (DSC), dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The results showed that the HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs presented a hydrodynamic particle size of 120.1 and 226.8 nm, with a polydispersity index of 0.057 and 0.207, a zeta potential of -31.2 and -45.7 mV, drug encapsulation efficiency of 44.52% and 44.94%, and drug-loaded content of 7.42% and 7.49%, respectively. The HCPT-loaded PEG-b-PLA NPs presented faster drug release rate compared to the HCPT-loaded PLA NPs. The HCPT-loaded PEG-b-PLA NPs presented higher cytotoxicity than the HCPT-loaded PLA NPs. These results suggested that the HCPT-loaded PEG-b-PLA NPs presented better characteristics for drug delivery compared to HCPT-loaded PLA NPs.

Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

PubMed

Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

2016-07-01

Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ramizol® encapsulation into extended release PLGA micro- and nanoparticle systems for subcutaneous and intramuscular administration: in vitro and in vivo evaluation.

PubMed

Wright, Leah; Rao, Shasha; Thomas, Nicky; Boulos, Ramiz A; Prestidge, Clive A

2018-04-11

Novel antibiotic Ramizol ® is advancing to clinical trials for the treatment of gastrointestinal Clostridium difficile associated disease. Despite this, previous studies have shown a rapid plasma clearance upon intravenous administration and low oral bioavailability indicating pure drug is unsuitable for systemic infection treatment following oral dosing. The current study aims to investigate the development of poly-lactic-(co-glycolic) acid (PLGA) particles to overcome this limitation and increase the systemic half-life following subcutaneous and intramuscular dosing. The development of new antibiotic treatments will help in combatting the rising incidence of antimicrobial resistance. Ramizol ® was encapsulated into PLGA nano and microparticles using nanoprecipitation and emulsification solvent evaporation techniques. Formulations were analyzed for particle size, loading level and encapsulation efficiency as well as in vitro drug release profiles. Final formulation was advanced to in vivo pharmacokinetic studies in Sprague-Dawley rats. Formulation technique showed major influence on particle size and loading levels with optimal loading of 9.4% and encapsulation efficiency of 92.06%, observed using emulsification solvent evaporation. Differences in formulation technique were also linked with subsequent differences in release profiles. Pharmacokinetic studies in Sprague-Dawley rats confirmed extended absorption and enhanced bioavailability following subcutaneous and intramuscular dosing with up to an 8-fold increase in T max and T 1/2 when compared to the oral and IV routes. Subcutaneous and intramuscular dosing of PLGA particles successfully increased systemic half-life and bioavailability of Ramizol ® . This formulation will allow further development of Ramizol ® for systemic infection eradication.

Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

NASA Astrophysics Data System (ADS)

Jain-Gupta, Neeta; Pothayee, Nipon; Pothayee, Nikorn; Tyler, Ronald; Caudell, David L.; Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S.; Sriranganathan, Nammalwar

2013-11-01

Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30-32 weight percentage of gentamicin. The zeta potential changed from -39 to -13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log10), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log10). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B. melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

Development of thermosensitive poly(n-isopropylacrylamide-co-((2-dimethylamino) ethyl methacrylate))-based nanoparticles for controlled drug release

NASA Astrophysics Data System (ADS)

Peng, Cheng-Liang; Tsai, Han-Min; Yang, Shu-Jyuan; Luo, Tsai-Yueh; Lin, Chia-Fu; Lin, Wuu-Jyh; Shieh, Ming-Jium

2011-07-01

Thermosensitive nanoparticles based on poly(N-isopropylacrylamide-co-((2-dimethylamino)ethylmethacrylate)) (poly(NIPA-co-DMAEMA)) copolymers were successfully fabricated by free radical polymerization. The lower critical solution temperature (LCST) of the synthesized nanoparticles was 41 °C and a temperature above which would cause the nanoparticles to undergo a volume phase transition from 140 to 100 nm, which could result in the expulsion of encapsulated drugs. Therefore, we used the poly(NIPA-co-DMAEMA) nanoparticles as a carrier for the controlled release of a hydrophobic anticancer agent, 7-ethyl-10-hydroxy-camptothecin (SN-38). The encapsulation efficiency and loading content of SN-38-loaded nanoparticles at an SN-38/poly(NIPA-co-DMAEMA) ratio of 1/10 (D/P = 1/10) were about 80% and 6.293%, respectively. Moreover, the release profile of SN-38-loaded nanoparticles revealed that the release rate at 42 °C (above LCST) was higher than that at 37 °C (below LCST), which demonstrated that the release of SN-38 could be controlled by increasing the temperature. The cytotoxicity of the SN-38-loaded poly(NIPA-co-DMAEMA) nanoparticles was investigated in human colon cancer cells (HT-29) to compare with the treatment of an anticancer drug, Irinotecan® (CPT-11). The antitumor efficacy evaluated in a C26 murine colon tumor model showed that the SN-38-loaded nanoparticles in combination with hyperthermia therapy efficiently suppressed tumor growth. The results indicate that these thermo-responsive nanoparticles are potential carriers for controlled drug delivery.

A new strategy to sustained release of ocular drugs by one-step drug-loaded microcapsule manufacturing in hydrogel punctal plugs.

PubMed

Xie, Jiajun; Wang, Changjun; Ning, Qingyao; Gao, Qi; Gao, Changyou; Gou, Zhongru; Ye, Juan

2017-11-01

To design an injectable hyaluronate (HA)-based hydrogel system that contains drug-loaded microcapsules as resorbable plugs to deliver ocular drugs. In-situ drug-loaded, core-shell-structured chitosan (CS)@HA microcapsules were fabricated via HA hydrosol collecting in electrospun bead-rich CS fibers under continuous stirring. An injectable and cytocompatible hydrogel system with different degrees of chemical crosslinking maintained viscoelastic and sustained drug release for a long-term period of time at body temperature in vitro. With the addition of adipic dihydrazide (ADH) or 1-Ethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (EDCI), HA hydrosols transited from liquid to solid state at the gel point, with the G'/G″ ratio varying between 1.43 and 5.32 as a function of crosslinker concentration in the hydrogel phase. Ofloxacin (OFL) release from the mechanically mixed hydrosol system (CS-HA-A0-E0) and the micro-encapsulated hydrosol formulation (CS@HA-A0-E0) were respectively over 80% and 51% of the total drug load leaching out within 24 h. As for the drug-mixed hydrogel systems with low (CS-HA-A0.06-E0.15) and high (CS-HA-A0.06-E0.30) crosslinking density, the OFL release rate reached 38.5 and 46.6% respectively, while the micro-encapsulated hydrogel systems with low (CS@HA-A0.06-E0.15) and high (CS@HA-A0.6-E0.30) showed only (11.9 ± 2.7)% and (17.4 ± 3.5)% drug release respectively. A one-step in-situ drug-capsulizing method is developed to fabricate a resorbable hydrogel punctal plug with extended drug release. The chemistry of the crosslinking reaction involves the formation of highly biocompatible HA derivatives. Thus, the hydrogel can be used directly in the tear drainage canalicular system.

Fabrication of a microfluidic device for studying the in situ drug-loading/release behavior of graphene oxide-encapsulated hydrogel beads.

PubMed

Veerla, Sarath Chandra; Kim, Da Reum; Yang, Sung Yun

2018-01-01

Controlled drug delivery system is highly important for not only prolonged the efficacy of drug but also cellular development for tissue engineering. A number of biopolymer composites and nanostructured carriers behave been used for the controlled drug delivery of therapeutics. Recently, in vitro microfluidic devices that mimic the human body have been developed for drug-delivery applications. A microfluidic channel was fabricated via a two-step process: (i) polydimethyl siloxane (PDMS) and curing agent were poured with a 10:2 mass ratio onto an acrylic mold with two steel pipes, and (ii) calcium alginate beads were synthesized using sodium alginate and calcium chloride solutions. Different amounts (10, 25, 50 μg) of graphene oxide (GO) were then added by Hummers method, and studies on the encapsulation and release of the model drug, risedronate (Ris), were performed using control hydrogel beads (pH 6.3), GO-containing beads (10GO, 25GO and 50GO), and different pH conditions. MC3T3 osteoblastic cells were cultured in a microchannel with Ris-loaded GO-hydrogel beads, and their proliferation, viability, attachment and spreading were assessed for a week. The spongy and textured morphology of pristine hydrogel beads was converted to flowery and rod-shaped structures in drug-loaded hydrogel beads at reduced pH (6.3) and at a lower concentration (10 μg) of GO. These latter 10GO drug-loaded beads rapidly released their cargo owing to the calcium phosphate deposited on the surface. Notably, beads containing a higher amount of GO (50GO) exhibited an extended drug-release profile. We further found that MC3T3 cells proliferated continuously in vitro in the microfluidic channel containing the GO-hydrogel system. MTT and live/dead assays showed similar proliferative potential of MC3T3 cells. Therefore, a microfluidic device with microchannels containing hydrogel beads formulated with different amounts of GO and tested under various pH conditions could be a promising system for controlled drug release. The GO and drug (risedronate, Rig) were directed loaded into a hydrogel placed in a microchannel. Through interactions such as hydrogen bonding between Go and the Rig-loaded GO-hydrogel beads, the bead-loaded microfluidic device supported MC3T3 proliferation and development as osteoblast without additional osteogenic differentiation supplements.

Drug-in-cyclodextrin-in-liposomes: A novel drug delivery system for flurbiprofen.

PubMed

Zhang, Lina; Zhang, Qi; Wang, Xin; Zhang, Wenji; Lin, Congcong; Chen, Fen; Yang, Xinggang; Pan, Weisan

2015-08-15

A novel delivery system based on drug-cyclodextrin (CD) complexation and liposomes has been developed to improve therapeutic effect. Three different means, i.e., co-evaporation (COE), co-ground (GR) and co-lyophilization (COL) and three different CDs (β-CD, HP-β-CD and SBE-β-CD) were contrasted to investigate the characteristics of the end products. FP/FP-CD loaded liposomes were obtained by thin layer evaporation technique. Size, zeta potential and encapsulation efficiency were investigated by light scattering analysis and minicolumn centrifugation. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) showed the amorphous form of complexes and spherical morphology of FP-HP-β-CD COE loaded liposomes. The pH 7.4 phosphate buffer solution (PBS) was selected as the medium for the in vitro release. Wistar rats were put into use to study the pharmacokinetic behavior in vivo. FP-HP-β-CD COE loaded liposomes showed the better physicochemical characters that followed the average particle size, polydispersity index, zeta potential and mean encapsulation efficiency 158±10 nm, 0.19±0.1, -12.4±0.1 mW and 56.1±0.5%, separately. The relative bioavailability of FP-HP-β-CD COE loaded liposomes was 420%, 201% and 402% compared with FP solution, FP-HP-β-CD and FP-liposomes, respectively. In conclusion, the novel delivery system improved the relative bioavailability of FP significantly and provided a perspective way for delivery of insoluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based model of osteoarthritis.

PubMed

Yeh, Chih-Chang; Su, Yu-Han; Lin, Yu-Jhe; Chen, Pin-Jyun; Shi, Chung-Sheng; Chen, Cheng-Nan; Chang, Hsin-I

2015-01-01

Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression.

Antitumor effects of hydroxycamptothecin-loaded poly[ethylene glycol]-poly [gamma-benzyl-L-glutamate] micelles against oral squamous cell carcinoma.

PubMed

Ding, Xue-Qiang; Chen, Dan; Wang, An-Xun; Li, Su; Chen, Yu; Wang, Ji

2007-01-01

Therapeutic use of hydroxycamptothecin (HCPT), a promising antitumor agent, is limited by its poor solubility and rapid destruction. Amphiphilic block copolymer micelle carriers possess significant potential for improving drug solubility and stability. Poly[ethylene glycol]-poly[gamma-benzyl-L-glutamate] (PEG-PBLG) micelles were prepared and loaded with the active lactone form of HCPT using an uncomplicated dialysis method. HPLC and scanning electron microscopy studies revealed an encapsulation efficiency of 56.8% and a core-shell figure with a mean diameter of 200 nm. Encapsulated HCPT lactone was compared with the less active, open ring-carboxylated HCPT-Na+ soluble form generated in vivo from the free active lactone for activity against oral squamous cell carcinoma. Cytotoxicity in vitro was measured in cultured Tca8113 cells by the MTT assay and microscopy techniques. The golden hamster cheek pouch squamous cell carcinoma model was employed for in vivo studies; encapsulated lactone and open ring-carboxylated forms of HCPT were administered intraperitoneally, followed by determinations of tumor growth rate and inhibition ratio. PEG-PBLG micelles were not cytotoxic in vitro. At 48 h of treatment, open ring-carboxylated HCPT proved significantly more cytotoxic in vitro than encapsulated HCPT lactone. At 96 h, however, the open ring-carboxylated and encapsulated drugs displayed comparable in vitro cytotoxicities. In the in vivo squamous cell carcinoma model, encapsulated HCPT lactone produced greater and more prolonged tumor suppression compared to the open ring-carboxylated form. The antitumor effects of HCPT/PEG-PBLG micelles against oral squamous cell carcinoma in vivo are concluded to be superior to those exerted by open ring-carboxylated HCPT.

Surface modification of endovascular stents with rosuvastatin and heparin-loaded biodegradable nanofibers by electrospinning.

PubMed

Janjic, Milka; Pappa, Foteini; Karagkiozaki, Varvara; Gitas, Christakis; Ktenidis, Kiriakos; Logothetidis, Stergios

2017-01-01

This study describes the development of drug-loaded nanofibrous scaffolds as a nanocoating for endovascular stents for the local and sustained delivery of rosuvastatin (Ros) and heparin (Hep) to injured artery walls after endovascular procedures via the electrospinning process. The proposed hybrid covered stents can promote re-endothelialization; improve endothelial function; reduce inflammatory reaction; inhibit neointimal hyperplasia of the injured artery wall, due to well-known pleiotropic actions of Ros; and prevent adverse events such as in-stent restenosis (ISR) and stent thrombosis (ST), through the antithrombotic action of Hep. Biodegradable nanofibers were prepared by dissolving cellulose acetate (AC) and Ros in N , N -dimethylacetamide (DMAc) and acetone-based solvents. The polymeric solution was electrospun (e-spun) into drug-loaded AC nanofibers onto three different commercially available stents (Co-Cr stent, Ni-Ti stent, and stainless steel stent), resulting in nonwoven matrices of submicron-sized fibers. Accordingly, Hep solution was further used for fibrous coating onto the engineered Ros-loaded stent. The functional encapsulation of Ros and Hep drugs into polymeric scaffolds further underwent physicochemical analysis. Morphological characterization took place via scanning electron microscopy (SEM) and atomic force microscopy (AFM) analyses, while scaffolds' wettability properties were obtained by contact angle (CA) measurements. The morphology of the drug-loaded AC nanofibers was smooth, with an average diameter of 200-800 nm, and after CA measurement, we concluded to the superhydrophobic nature of the engineered scaffolds. In vitro release rates of the pharmaceutical drugs were determined using a high-performance liquid chromatography assay, which showed that after the initial burst, drug release was controlled slowly by the degradation of the polymeric materials. These results imply that AC nanofibers encapsulated with Ros and Hep drugs have great potential in the development of endovascular grafts with anti-thrombogenic properties that can accelerate the re-endothelialization, reduce the neointimal hyperplasia and inflammatory reaction, and improve the endothelial function.

Preparation of a novel composite nanofiber gel-encapsulated human placental extract through layer-by-layer self-assembly

PubMed Central

LIU, GUOHUI; CHEN, XI; ZHOU, WU; YANG, SHUHUA; YE, SHUNAN; CAO, FAQI; LIU, YI; XIONG, YUAN

2016-01-01

Aqueous human placenta extract (HPE) has been previously used to treat chronic soft tissue ulcer; however, the optimal dosage of HPE has yet to be elucidated. The present study investigated a novel nanofiber gel composed through layer-by-layer (LbL) self-assembly, in which HPE was encapsulated. IKVAV, RGD, RAD16 and FGL-PA were screened and combined to produce an optimal vehicle nanofiber gel through LbL assembly. Subsequently, the aqueous HPE was encapsulated into this nanofiber at the appropriate concentration, and the morphology, particle size, drug loading efficacy, encapsulation rate, release efficiency and structure validation were detected. The encapsulation efficiency of all three HPE samples was >90%, the nanofiber gel exhibited a slow releasing profile, and the structure of HPE encapsulated in the nanofiber gel was unvaried. In conclusion, this type of novel composite nanocapsules may offer a promising delivery system for HPE. PMID:27073463

Practical preparation procedures for docetaxel-loaded nanoparticles using polylactic acid-co-glycolic acid.

PubMed

Keum, Chang-Gu; Noh, Young-Wook; Baek, Jong-Suep; Lim, Ji-Ho; Hwang, Chan-Ju; Na, Young-Guk; Shin, Sang-Chul; Cho, Cheong-Weon

2011-01-01

Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), are the most intensively investigated polymers for drug delivery systems. The objective of this study was to explore fully the development of a PLGA nanoparticle drug delivery system for alternative preparation of a commercial formulation. In our nanoparticle fabrication, our purpose was to compare various preparation parameters. Docetaxel-loaded PLGA nanoparticles were prepared by a single emulsion technique and solvent evaporation. The nanoparticles were characterized by various techniques, including scanning electron microscopy for surface morphology, dynamic light scattering for size and zeta potential, x-ray photoelectron spectroscopy for surface chemistry, and high-performance liquid chromatography for in vitro drug release kinetics. To obtain a smaller particle, 0.2% polyvinyl alcohol, 0.03% D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), 2% Poloxamer 188, a five-minute sonication time, 130 W sonication power, evaporation with magnetic stirring, and centrifugation at 8000 rpm were selected. To increase encapsulation efficiency in the nanoparticles, certain factors were varied, ie, 2-5 minutes of sonication time, 70-130 W sonication power, and 5-25 mg drug loading. A five-minute sonication time, 130 W sonication power, and a 10 mg drug loading amount were selected. Under these conditions, the nanoparticles reached over 90% encapsulation efficiency. Release kinetics showed that 20.83%, 40.07%, and 51.5% of the docetaxel was released in 28 days from nanoparticles containing Poloxamer 188, TPGS, or polyvinyl alcohol, respectively. TPGS and Poloxamer 188 had slower release kinetics than polyvinyl alcohol. It was predicted that there was residual drug remaining on the surface from x-ray photoelectron spectroscopy. Our research shows that the choice of surfactant is important for controlled release of docetaxel.

An alternative choice of lidocaine-loaded liposomes: lidocaine-loaded lipid-polymer hybrid nanoparticles for local anesthetic therapy.

PubMed

Wang, Jianguo; Zhang, Laizhu; Chi, Huimin; Wang, Shilei

2016-05-01

The skin permeation enhancement of local anesthetics by newer innovative nanotechnologies has been an appealing field recently. However, which nanocarrier is better for drug loading and has better stability? Therefore, the aim of our study was to compare two kinds of nanocarriers: liposomes and lipid-polymer hybrid nanoparticles (LPNs) for lidocaine (LA) delivery. LA-loaded liposomes (LA-LPs) and LPNs (LA-LPNs) were prepared. Two kinds of nanocarriers were characterized in terms of particle size, zeta potential, drug encapsulation efficiency (EE), drug release, and stability. Their in vitro skin permeation was studied using a Franz diffusion cell mounted with depilated mouse skin in vitro. In vivo local anesthetic effects of LA containing formulations were evaluated by tail flick latency (TFL) test using a tail-flick measuring device. Compared with LA-LPs, LA-LPNs showed significantly better in vitro skin permeation ability and in vivo local anesthetic effects. The results demonstrated that LPNs could improve the efficacy of drugs to higher levels than LPs and free drugs, thus could serve as an effective drug system for LA loading for local anesthetic therapy.

Efficient co-delivery of immiscible hydrophilic/hydrophobic chemotherapeutics by lipid emulsions for improved treatment of cancer

PubMed Central

Zhang, Bo; Song, Yunmei; Wang, Tianqi; Yang, Shaomei; Zhang, Jing; Liu, Yongjun; Zhang, Na; Garg, Sanjay

2017-01-01

Combinational nanomedicine is becoming a topic of much interest in cancer therapy, although its translation into the clinic remains extremely challenging. One of the main obstacles lies in the difficulty to efficiently co-deliver immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co-delivery abilities between co-loaded LEs and mixture formulation. Multiple oxaliplatin/irinotecan drug–phospholipid complexes (DPCs) were formulated. Co-loaded LEs were prepared using DPC technique to efficiently encapsulate both drugs. Co-loaded LEs exhibited uniform particle size distribution, desired stability and synchronous release profiles in both drugs. Co-loaded LEs demonstrated superior anti-tumor activity compared with the simple solution mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers could co-deliver both drugs into the same cells more efficiently and exhibited the optimized synergistic effect. These results indicate that co-loaded LEs could be a desired formulation for enhanced cancer therapy with potential application prospects. The comparison between co-loaded LEs and mixture formulation is significant for pharmaceutical designs aimed at co-delivery of multiple drugs. PMID:28435264

Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

NASA Astrophysics Data System (ADS)

Li, Fengxia; Li, Xiaoli; Li, Bin

2011-11-01

In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 μm. Magnetic Fe 3O 4 was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h.

Oxcarbazepine-loaded polymeric nanoparticles: development and permeability studies across in vitro models of the blood–brain barrier and human placental trophoblast

PubMed Central

Lopalco, Antonio; Ali, Hazem; Denora, Nunzio; Rytting, Erik

2015-01-01

Encapsulation of antiepileptic drugs (AEDs) into nanoparticles may offer promise for treating pregnant women with epilepsy by improving brain delivery and limiting the transplacental permeability of AEDs to avoid fetal exposure and its consequent undesirable adverse effects. Oxcarbazepine-loaded nanoparticles were prepared by a modified solvent displacement method from biocompatible polymers (poly(lactic-co-glycolic acid) [PLGA] with or without surfactant and PEGylated PLGA [Resomer® RGPd5055]). The physical properties of the developed nanoparticles were determined with subsequent evaluation of their permeability across in vitro models of the blood–brain barrier (hCMEC/D3 cells) and human placental trophoblast cells (BeWo b30 cells). Oxcarbazepine-loaded nanoparticles with encapsulation efficiency above 69% were prepared with sizes ranging from 140–170 nm, polydispersity indices below 0.3, and zeta potential values below -34 mV. Differential scanning calorimetry and X-ray diffraction studies confirmed the amorphous state of the nanoencapsulated drug. The apparent permeability (Pe) values of the free and nanoencapsulated oxcarbazepine were comparable across both cell types, likely due to rapid drug release kinetics. Transport studies using fluorescently-labeled nanoparticles (loaded with coumarin-6) demonstrated increased permeability of surfactant-coated nanoparticles. Future developments in enzyme-prodrug therapy and targeted delivery are expected to provide improved options for pregnant patients with epilepsy. PMID:25792832

Oxcarbazepine-loaded polymeric nanoparticles: development and permeability studies across in vitro models of the blood-brain barrier and human placental trophoblast.

PubMed

Lopalco, Antonio; Ali, Hazem; Denora, Nunzio; Rytting, Erik

2015-01-01

Encapsulation of antiepileptic drugs (AEDs) into nanoparticles may offer promise for treating pregnant women with epilepsy by improving brain delivery and limiting the transplacental permeability of AEDs to avoid fetal exposure and its consequent undesirable adverse effects. Oxcarbazepine-loaded nanoparticles were prepared by a modified solvent displacement method from biocompatible polymers (poly(lactic-co-glycolic acid) [PLGA] with or without surfactant and PEGylated PLGA [Resomer(®) RGPd5055]). The physical properties of the developed nanoparticles were determined with subsequent evaluation of their permeability across in vitro models of the blood-brain barrier (hCMEC/D3 cells) and human placental trophoblast cells (BeWo b30 cells). Oxcarbazepine-loaded nanoparticles with encapsulation efficiency above 69% were prepared with sizes ranging from 140-170 nm, polydispersity indices below 0.3, and zeta potential values below -34 mV. Differential scanning calorimetry and X-ray diffraction studies confirmed the amorphous state of the nanoencapsulated drug. The apparent permeability (Pe ) values of the free and nanoencapsulated oxcarbazepine were comparable across both cell types, likely due to rapid drug release kinetics. Transport studies using fluorescently-labeled nanoparticles (loaded with coumarin-6) demonstrated increased permeability of surfactant-coated nanoparticles. Future developments in enzyme-prodrug therapy and targeted delivery are expected to provide improved options for pregnant patients with epilepsy.

Preparation and in vitro evaluation of heparin-loaded polymeric nanoparticles.

PubMed

Jiao, Y Y; Ubrich, N; Marchand-Arvier, M; Vigneron, C; Hoffman, M; Maincent, P

2001-01-01

Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated with two biodegradable polymers (poly-E-caprolactone [PCL] and poly (D, L-lactic-co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradable positively charged polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation method, using a high-pressure homogenization device. The encapsulation efficiency and heparin release profiles were studied as a function of the type of polymers employed (alone or in combination) and the concentration of heparin. Optimal encapsulation efficiency was observed when 5000 IU of heparin were incorporated in the first emulsion. High drug entrapment efficiency was observed in both Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA and PCL nanoparticles (<14%). The use of the two types of Eudragit in combination with PCL and PLAGA increased the encapsulation efficiency compared with these two biodegradable polymers used alone; however, the in vitro drug release was not modified and remained low. On the other hand, the addition of esterase to the dissolution medium resulted in a significant increase in heparin release. The in vitro biological activity of released heparin, evaluated by measuring the anti-Xa activity by a colorimetric assay, was conserved after the encapsulation process.

Encapsulation and controlled release of rapamycin from polycaprolactone nanoparticles prepared by membrane micromixing combined with antisolvent precipitation.

PubMed

Othman, Rahimah; Vladisavljevic, Goran T; Nagy, Zoltan K; Holdich, Richard Graham

2016-09-30

Rapamycin loaded polycaprolactone nanoparticles (RAPA-PCL NPs) with a low polydispersity index of 0.006-0.073 were produced by anti-solvent precipitation using a ringed stainless steel membrane with 10-μm diameter laser-drilled pores. The organic phase composed of 6 g L -1 of PCL and 0.6-3.0 g L -1 of RAPA in acetone was injected through the membrane at 140 L m -2 h -1 into 0.2 wt% aqueous polyvinyl alcohol solution stirred at 1300 rpm, resulting in a Z-average mean of 189-218 nm, a drug encapsulation efficiency of 98.8-98.9 % and a drug loading in the NPs of 9-33 %. The encapsulation of RAPA was confirmed by UV-Vis spectroscopy, XRD, DSC, and ATR-FTIR. The disappearance of sharp characteristic peaks of crystalline RAPA in the XRD pattern of RAPA-PCL NPs revealed that the drug was molecularly dispersed in the polymer matrix or present in individual amorphous domains. The rate of drug release in pure water was negligible due to low aqueous solubility of RAPA. RAPA-PCL NPs released more than 91 % of their drug cargo after 2.5 h in the release medium composed of 0.78-1.5 M of the hydrotropic agent N,N-diethylnicotinamide (DENA), 10 vol% of ethanol, and 2 vol% of Tween 20 in phosphate buffered saline. The release rate of RAPA was faster when the concentra-tion of DENA in the dissolution medium was higher. The dissolution of RAPA was slower when the drug was embedded in the PCL matrix of the NPs than dispersed in the form of pure RAPA nanocrystals.

Highly water-soluble, porous, and biocompatible boron nitrides for anticancer drug delivery.

PubMed

Weng, Qunhong; Wang, Binju; Wang, Xuebin; Hanagata, Nobutaka; Li, Xia; Liu, Dequan; Wang, Xi; Jiang, Xiangfen; Bando, Yoshio; Golberg, Dmitri

2014-06-24

Developing materials for "Nano-vehicles" with clinically approved drugs encapsulated is envisaged to enhance drug therapeutic effects and reduce the adverse effects. However, design and preparation of the biomaterials that are porous, nontoxic, soluble, and stable in physiological solutions and could be easily functionalized for effective drug deliveries are still challenging. Here, we report an original and simple thermal substitution method to fabricate perfectly water-soluble and porous boron nitride (BN) materials featuring unprecedentedly high hydroxylation degrees. These hydroxylated BNs are biocompatible and can effectively load anticancer drugs (e.g., doxorubicin, DOX) up to contents three times exceeding their own weight. The same or even fewer drugs that are loaded on such BN carriers exhibit much higher potency for reducing the viability of LNCaP cancer cells than free drugs.

Nanoprecipitation process: From encapsulation to drug delivery.

PubMed

Martínez Rivas, Claudia Janeth; Tarhini, Mohamad; Badri, Waisudin; Miladi, Karim; Greige-Gerges, Hélène; Nazari, Qand Agha; Galindo Rodríguez, Sergio Arturo; Román, Rocío Álvarez; Fessi, Hatem; Elaissari, Abdelhamid

2017-10-30

Drugs encapsulation is a suitable strategy in order to cope with the limitations of conventional dosage forms such as unsuitable bioavailability, stability, taste, and odor. Nanoprecipitation technique has been used in the pharmaceutical and agricultural research as clean alternative for other drug carrier formulations. This technique is based on precipitation mechanism. Polymer precipitation occurs after the addition of a non-solvent to a polymer solution in four steps mechanism: supersaturation, nucleation, growth by condensation, and growth by coagulation that leads to the formation of polymer nanoparticles or aggregates. The scale-up of laboratory-based nanoprecipitation method shows a good reproducibility. In addition, flash nanoprecipitation is a good strategy for industrial scale production of nanoparticles. Nanoprecipitation is usually used for encapsulation of hydrophobic or hydrophilic compounds. Nanoprecipitation was also shown to be a good alternative for the encapsulation of natural compounds. As a whole, process and formulation related parameters in nanoprecipitation technique have critical effect on nanoparticles characteristics. Biodegradable or non-biodegradable polymers have been used for the preparation of nanoparticles intended to in vivo studies. Literature studies have demonstrated the biodistribution of the active loaded nanoparticles in different organs after administration via various routes. In general, in vitro drug release from nanoparticles prepared by nanoprecipitation includes two phases: a first phase of "burst release" which is followed by a second phase of prolonged release. Moreover, many encapsulated active molecules have been commercialized in the pharmaceutical market. Copyright © 2017 Elsevier B.V. All rights reserved.

Penetration of blood-brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system.

PubMed

Zou, Dan; Wang, Wei; Lei, Daoxi; Yin, Ying; Ren, Peng; Chen, Jinju; Yin, Tieying; Wang, Bochu; Wang, Guixue; Wang, Yazhou

2017-01-01

For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.

Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

PubMed Central

Vicari, Luisa; Musumeci, Teresa; Giannone, Ignazio; Adamo, Luana; Conticello, Concetta; De Maria, Ruggero; Pignatello, Rosario; Puglisi, Giovanni; Gulisano, Massimo

2008-01-01

Background PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor® EL (polyethoxylated castor oil) and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration. Methods In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC. Results NS loaded with 3% PTX (w/w) had a mean size < 250 nm and a polydispersity index of 0.4 after freeze-drying with 0.5% HP-Cyd as cryoprotector. PTX encapsulation efficiency was 30% and NS showed a prolonged drug release in vitro. An increase of the cytotoxic effect of PTX-NS was observed with respect to free PTX in all cell lines tested. Conclusion These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies. PMID:18657273

Self-degrading niosomes for encapsulation of hydrophilic and hydrophobic drugs: An efficient carrier for cancer multi-drug delivery.

PubMed

Sharma, Varsha; Anandhakumar, Sundaramurthy; Sasidharan, Manickam

2015-11-01

In this study, we have examined the encapsulation and release of hydrophilic and hydrophobic drugs in self-degrading niosomes as a unique method for anticancer therapy. Niosomes were prepared by amphiphilic self-assembly of Tween 80 and cholesterol through film hydration method. Encapsulation studies with two active molecules curcumin and doxorubicin hydrochloride (Dox) showed that curcumin is supposed to accumulate in the shell whereas Dox accumulates in the inner aqueous core of the niosome. Confocal studies indicated that nile red adsorbs preferentially to the head group of the Tween 80 and forms two separate layers in the shell. It was also seen that the niosomes undergo self-degradation in PBS through a sequential process, forming interconnected pores followed by complete collapse after 1week. The release profile shows two phases: i) initial Dox release in the first two days, followed by ii) curcumin release over 7days. Enhanced (synergistic) cytotoxicity was observed for dual-drug loaded niosomes against HeLa cell lines. Thus these niosomes are shown to offer a promising delivery system for hydrophobic and hydrophilic drugs collectively. Copyright © 2015 Elsevier B.V. All rights reserved.

A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies.

PubMed

Nallamothu, Ramakrishna; Wood, George C; Kiani, Mohammad F; Moore, Bob M; Horton, Frank P; Thoma, Laura A

2006-01-01

Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion process. Cyclic arginine-glycine-aspartic acid (RGD) peptides with affinity for alphav beta3-integrins overexpressed on tumor vascular endothelial cells were coupled to the distal end of polyethylene glycol (PEG) on the liposomes sterically stabilized with PEG (non-targeted liposomes; LCLs). Effect of lipid concentration, drug-to-lipid ratio, cholesterol, and DSPE-PEG content in the formulation on CA4 loading and its release from the liposomes was studied. Total liposomal CA4 levels obtained increased with increasing lipid concentration in the formulation. As the drug-to-lipid ratio increased from 10:100 to 20:100, total drug in the liposome formulation increased from 1.05+/-0.11 mg/mL to 1.55+/-0.13 mg/mL, respectively. When the drug-to-lipid ratio was further raised to 40:100, the total drug in liposome formulation did not increase, but the amount of free drug increased significantly, thereby decreasing the percent of entrapped drug. Increasing cholesterol content in the formulation decreased drug loading. In vitro drug leakage from the liposomes increased with increase in drug-to-lipid ratio or DSPE-PEG content in the formulation; whereas increasing cholesterol content of the formulation up to 30 mol-percent, decreased CA4 leakage from the liposomes. Ligand coupling to the liposome surface increased drug leakage as a function of ligand density. Optimized liposome formulation with 100 mM lipid concentration, 20:100 drug-to-lipid ratio, 30 mol-percent cholesterol, 4 mol-percent DSPE-PEG, and 1 mol-percent DSPE-PEG-maleimide content yielded 1.77+/-0.14 mg/mL liposomal CA4 with 85.70+/-1.71% of this being entrapped in the liposomes. These liposomes, with measured size of 123.84+/-41.23 nm, released no significant amount of the encapsulated drug over 48 h at 37 degrees C.

The presence of glutamate residues on the PAS sequence of the stimuli-sensitive nano-ferritin improves in vivo biodistribution and mitoxantrone encapsulation homogeneity.

PubMed

Falvo, Elisabetta; Malagrinò, Francesca; Arcovito, Alessandro; Fazi, Francesco; Colotti, Gianni; Tremante, Elisa; Di Micco, Patrizio; Braca, Aldo; Opri, Roberta; Giuffrè, Alessandro; Fracasso, Giulio; Ceci, Pierpaolo

2018-04-10

A genetically engineered human ferritin heavy chain (HFt)-based construct has been recently shown by our group to efficiently entrap and deliver doxorubicin to cancer cells. This construct, named HFt-MP-PAS, contained a tumor-selective sequence (MP) responsive to proteolytic cleavage by tumor proteases (MMPs), located between each HFt subunit and an outer shielding polypeptide sequence rich in proline (P), serine (S) and alanine (A) residues (PAS). HFt-MP-PAS displayed excellent therapeutic efficacy in xenogenic pancreatic and head and neck cancer models in vivo, leading to a significant increase in overall animal survivals. Here we report a new construct obtained by the genetic insertion of two glutamate residues in the PAS sequence of HFt-MP-PAS. Such new construct, named HFt-MP-PASE, is characterized by improved performances as drug biodistribution in a xenogenic pancreatic cancer model in vivo. Moreover, HFt-MP-PASE efficiently encapsulates the anti-cancer drug mitoxantrone (MIT), and the resulting MIT-loaded nanoparticles proved to be more soluble and monodispersed than the HFt-MP-PAS counterparts. Importantly, in vitro MIT-loaded HFt-MP-PASE kills several cancer cell lines of different origin (colon, breast, sarcoma and pancreas) at least as efficiently as the free drug. Finally, our MIT loaded protein nanocages allowed in vivo an impressive incrementing of the drug accumulation in the tumor with respect to the free drug. Copyright © 2018 Elsevier B.V. All rights reserved.

Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model

PubMed Central

Chen, Yan; Zheng, Xue-Lian; Fang, Dai-Long; Yang, Yang; Zhang, Jin-Kun; Li, Hui-Li; Xu, Bei; Lei, Yi; Ren, Ke; Song, Xiang-Rong

2014-01-01

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic. PMID:24552875

Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles

PubMed Central

Pakulska, Malgosia M.; Elliott Donaghue, Irja; Obermeyer, Jaclyn M.; Tuladhar, Anup; McLaughlin, Christopher K.; Shendruk, Tyler N.; Shoichet, Molly S.

2016-01-01

Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules. PMID:27386554

Solubilization Behavior of Polyene Antibiotics in Nanomicellar System: Insights from Molecular Dynamics Simulation of the Amphotericin B and Nystatin Interactions with Polysorbate 80.

PubMed

Mobasheri, Meysam; Attar, Hossein; Rezayat Sorkhabadi, Seyed Mehdi; Khamesipour, Ali; Jaafari, Mahmoud Reza

2015-12-24

Amphotericin B (AmB) and Nystatin (Nys) are the drugs of choice for treatment of systemic and superficial mycotic infections, respectively, with their full clinical potential unrealized due to the lack of high therapeutic index formulations for their solubilized delivery. In the present study, using a coarse-grained (CG) molecular dynamics (MD) simulation approach, we investigated the interaction of AmB and Nys with Polysorbate 80 (P80) to gain insight into the behavior of these polyene antibiotics (PAs) in nanomicellar solution and derive potential implications for their formulation development. While the encapsulation process was predominantly governed by hydrophobic forces, the dynamics, hydration, localization, orientation, and solvation of PAs in the micelle were largely controlled by hydrophilic interactions. Simulation results rationalized the experimentally observed capability of P80 in solubilizing PAs by indicating (i) the dominant kinetics of drugs encapsulation over self-association; (ii) significantly lower hydration of the drugs at encapsulated state compared with aggregated state; (iii) monomeric solubilization of the drugs; (iv) contribution of drug-micelle interactions to the solubilization; (v) suppressed diffusivity of the encapsulated drugs; (vi) high loading capacity of the micelle; and (vii) the structural robustness of the micelle against drug loading. Supported from the experimental data, our simulations determined the preferred location of PAs to be the core-shell interface at the relatively shallow depth of 75% of micelle radius. Deeper penetration of PAs was impeded by the synergistic effects of (i) limited diffusion of water; and (ii) perpendicular orientation of these drug molecules with respect to the micelle radius. PAs were solvated almost exclusively in the aqueous poly-oxyethylene (POE) medium due to the distance-related lack of interaction with the core, explaining the documented insensitivity of Nys solubilization to drug-core compatibility in detergent micelles. Based on the obtained results, the dearth of water at interior sites of micelle and the large lateral occupation space of PAs lead to shallow insertion, broad radial distribution, and lack of core interactions of the amphiphilic drugs. Hence, controlled promotion of micelle permeability and optimization of chain crowding in palisade layer may help to achieve more efficient solubilization of the PAs.

PTX-loaded three-layer PLGA/CS/ALG nanoparticle based on layer-by-layer method for cancer therapy.

PubMed

Wang, Fang; Yuan, Jian; Zhang, Qian; Yang, Siqian; Jiang, Shaohua; Huang, Chaobo

2018-05-17

Poly (lactic-co-glycolic acid) (PLGA) nanoparticles are an ideal paclitaxel (PTX)-carrying system due to its biocompatibility and biodegradability. But it possessed disadvantage of drug burst release. In this research, a layer-by-layer deposition of chitosan (CS) and sodium alginate (ALG) was applied to modify the PLGA nanoparticles. The surface charges and morphology of the PLGA, PLGA/CS and PLGA/CS/ALG particles was measured by capillary electrophoresis and SEM and TEM, respectively. The drug encapsulation and loading efficiency were confirmed by ultraviolet spectrophotometer. The nanoparticles were stable and exhibited controlled drug release performance, with good cytotoxicity to human lung carcinoma cells (HepG 2). Cumulatively, our research suggests that this kind of three-layer nanoparticle with LbL-coated shield has great properties to act as a novel drug-loaded system.

Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo.

PubMed

Gou, MaLing; Men, Ke; Shi, HuaShan; Xiang, MingLi; Zhang, Juan; Song, Jia; Long, JianLin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, ZhiYong

2011-04-01

Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 ± 0.011) with a mean particle size of 27.3 ± 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 ± 1.02%, and drug loading of 12.95 ± 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t(1/2) and AUC of curcumin in vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesis in vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cells in vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg(-1) curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

Characterization and anticancer potential of ferulic acid-loaded chitosan nanoparticles against ME-180 human cervical cancer cell lines

NASA Astrophysics Data System (ADS)

Panwar, Richa; Sharma, Asvene K.; Kaloti, Mandeep; Dutt, Dharm; Pruthi, Vikas

2016-08-01

Ferulic acid (FA) is a widely distributed hydroxycinnamic acid found in various cereals and fruits exhibiting potent antioxidant and anticancer activities. However, due to low solubility and permeability, its availability to biological systems is limited. Non-toxic chitosan-tripolyphosphate pentasodium (CS-TPP) nanoparticles (NPs) are used to load sparingly soluble molecules and drugs, increasing their bioavailability. In the present work, we have encapsulated FA into the CS-TPP NPs to increase its potential as a therapeutic agent. Different concentrations of FA were tested to obtain optimum sized FA-loaded CS-TPP nanoparticles (FA/CS-TPP NPs) by ionic gelation method. Nanoparticles were characterized by scanning electron microscopy, Fourier transformation infrared spectroscopy (FTIR), thermogravimetric analyses and evaluated for their anticancer activity against ME-180 human cervical cancer cell lines. The FTIR spectra confirmed the encapsulation of FA and thermal analysis depicted its degradation profile. A concentration-dependent relationship between FA encapsulation efficiency and FA/CS-TPP NPs diameter was observed. Smooth and spherical FA-loaded cytocompatible nanoparticles with an average diameter of 125 nm were obtained at 40 µM FA conc. The cytotoxicity of 40 µM FA/CS-TPP NPs against ME-180 cervical cancer cell lines was found to be higher as compared to 40 µM native FA. Apoptotic morphological changes as cytoplasmic remnants and damaged wrinkled cells in ME-180 cells were visualized using scanning electron microscopic and fluorescent microscopic techniques. Data concluded that chitosan enveloped FA nanoparticles could be exploited as an excellent therapeutic drug against cancer cells proliferation.

Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy.

PubMed

Zhang, Wenli; Li, Caibin; Jin, Ya; Liu, Xinyue; Wang, Zhiyu; Shaw, John P; Baguley, Bruce C; Wu, Zimei; Liu, Jianping

2018-11-01

To improve drug retention in carriers for amphiphilic asulacrine (ASL), a novel active loading method using micelle gradient was developed to fabricate the ASL-loaded multiseed liposomes (ASL-ML). The empty ML were prepared by hydrating a thin film with empty micelles. Then the micelles in liposomal compartment acting as 'micelle pool' drove the drug to be loaded after the outer micelles were removed. Some reasoning studies including critical micelle concentration (CMC) determination, influencing factors tests on entrapment efficiency (EE), structure visualization, and drug release were carried out to explore the mechanism of active loading, ASL location, and the structure of ASL-ML. Comparisons were made between pre-loading and active loading method. Finally, the extended drug retention capacity of ML was evaluated through pharmacokinetic, drug tissue irritancy, and in vivo anti-tumor activity studies. Comprehensive results from fluorescent and transmission electron microscope (TEM) observation, encapsulation efficiency (EE) comparison, and release studies demonstrated the formation of ML-shell structure for ASL-ML without inter-carrier fusion. The location of drug mainly in inner micelles as well as the superiority of post-loading to the pre-loading method , in which drug in micelles shifted onto the bilayer membrane was an additional positive of this delivery system. It was observed that the drug amphiphilicity and interaction of micelles with drug were the two prerequisites for this active loading method. The extended retention capacity of ML has been verified through the prolonged half-life, reduced paw-lick responses in rats, and enhanced tumor inhibition in model mice. In conclusion, ASL-ML prepared by active loading method can effectively load drug into micelles with expected structure and improve drug retention.

Enhanced colloidal stability, solubility and rapid dissolution of resveratrol by nanocomplexation with soy protein isolate.

PubMed

Pujara, Naisarg; Jambhrunkar, Siddharth; Wong, Kuan Yau; McGuckin, Michael; Popat, Amirali

2017-02-15

The polyphenolic compound resveratrol has received significant attention due to its many pharmacological actions such as anti-cancer, anti-inflammatory, antioxidant and antimicrobial activities. However, poor solubility and stability are major impediments for resveratrol's clinical effectiveness. In this work we have encapsulated resveratrol into soy protein isolate nanoparticles using a simple rotary evaporation technique. Resveratrol-loaded nanoparticles were around 100nm in diameter and negatively charged. Nano-encapsulated resveratrol was found to be in amorphous form and showed more than two times higher solubility with significantly increased dissolution when compared to free resveratrol. Finally, an in-vitro NF-κB inhibition assay revealed that encapsulated resveratrol was stable and retained bioactivity. This new formulation of resveratrol has the potential to boost the clinical effectiveness of this drug and could be utilised for other poorly soluble hydrophobic drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Polymer Coated Echogenic Lipid Nanoparticles with Dual Release Triggers

PubMed Central

Nahire, Rahul; Haldar, Manas K.; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H.; Katti, Kalpana S.; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

2013-01-01

Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 minutes simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging. PMID:23394107

Neuropeptide Y Y1 receptors meditate targeted delivery of anticancer drug with encapsulated nanoparticles to breast cancer cells with high selectivity and its potential for breast cancer therapy.

PubMed

Li, Juan; Shen, Zheyu; Ma, Xuehua; Ren, Wenzhi; Xiang, Lingchao; Gong, An; Xia, Tian; Guo, Junming; Wu, Aiguo

2015-03-11

By enabling nanoparticle-based drug delivery system to actively target cancer cells with high selectivity, active targeted molecules have attracted great attention in the application of nanoparticles for anticancer drug delivery. However, the clinical application of most active targeted molecules in breast cancer therapy is limited, due to the low expression of their receptors in breast tumors or coexpression in the normal and tumor breast tissues. Here, a neuropeptide Y Y1 receptors ligand PNBL-NPY, as a novel targeted molecule, is conjugated with anticancer drug doxorubicin encapsulating albumin nanoparticles to investigate the effect of Y1 receptors on the delivery of drug-loaded nanoparticles to breast cancer cells and its potential for breast cancer therapy. The PNBL-NPY can actively recognize and bind to the Y1 receptors that are significantly overexpressed on the surface of the breast cancer cells, and the drug-loaded nanoparticles are delivered directly into the cancer cells through internalization. This system is highly selective and able to distinguish the breast cancer cells from the normal cells, due to normal breast cells that express Y2 receptors only. It is anticipated that this study may provide a guidance in the development of Y1 receptor-based nanoparticulate drug delivery system for a safer and more efficient breast cancer therapy.

Modifying the release of leuprolide from spray dried OED microparticles.

PubMed

Alcock, R; Blair, J A; O'Mahony, D J; Raoof, A; Quirk, A V

2002-08-21

A range of oligosaccharide ester derivatives (OEDs) have been designed as drug delivery matrices for controlled release. The synthetic hormone analogue, leuprolide, was encapsulated within these matrices using hydrophobic ion pairing and solvent spray drying. The particles produced modified the release of leuprolide in vitro (dissolution in phosphate buffered saline) and in vivo (subcutaneous and pulmonary delivery in the rat). Release rate was dependent on drug loading and could be manipulated by choice of OED and by combining different OEDs in different ratios. Leuprolide encapsulated in the OEDs retained biological activity as evidenced by elevation in plasma luteinising hormone levels following subcutaneous injection of leuprolide recovered from OED particles in vitro prior to in vivo administration.

Improvement of dissolution behavior of poorly water soluble drugs by biodegradable polymeric submicron carriers containing sparingly methylated β-cyclodextrin.

PubMed

Singhavi, Dilesh J; Khan, Shagufta; Yeole, Pramod G

2013-04-01

The objective of this study was to develop submicron carriers of two drugs that are practically insoluble in water, i.e. meloxicam and aceclofenac, to improve their dissolution behavior. The phase solubility of the drugs was studied using different concentrations of sparingly methylated β-cyclodextrin, Kleptose(®) Crysmeβ (Crysmeb), in the presence and absence of 0.2 % w/v water-soluble chitosan. Drug-loaded submicron particles (SMPs) were prepared using chitosan chlorhydrate and Crysmeb by the ionotropic gelation method. The SMPs were characterized in terms of powder X-ray diffraction, Fourier transforms infrared spectroscopy, size determination, process yield, drug loading, encapsulation efficiency, surface morphology and in vitro release. The drug loading in the SMPs was enhanced in the presence of Crysmeb. The in vitro drug release was found to be enhanced with SMPs prepared using higher concentrations of Crysmeb. These results indicate that SMPs formed from chitosan chlorhydrate and Crysmeb are promising submicron carriers for enhancing the dissolution of meloxicam and aceclofenac.

Synthesis of polymer-lipid nanoparticles for image-guided delivery of dual modality therapy.

PubMed

Mieszawska, Aneta J; Kim, YongTae; Gianella, Anita; van Rooy, Inge; Priem, Bram; Labarre, Matthew P; Ozcan, Canturk; Cormode, David P; Petrov, Artiom; Langer, Robert; Farokhzad, Omid C; Fayad, Zahi A; Mulder, Willem J M

2013-09-18

For advanced treatment of diseases such as cancer, multicomponent, multifunctional nanoparticles hold great promise. In the current study we report the synthesis of a complex nanoparticle (NP) system with dual drug loading as well as diagnostic properties. To that aim we present a methodology where chemically modified poly(lactic-co-glycolic) acid (PLGA) polymer is formulated into a polymer-lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the polymeric core and an anti-angiogenic drug sorafenib (SRF) in the lipidic corona. The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In addition, a near-infrared (NIR) Cy7 dye was incorporated in the coating. To fabricate the NP we used a microfluidics-based technique that offers unique NP synthesis conditions, which allowed for encapsulation and fine-tuning of optimal ratios of all the NP components. NP phantoms could be visualized with computed tomography (CT) and near-infrared (NIR) fluorescence imaging. We observed timed release of the encapsulated drugs, with fast release of the corona drug SRF and delayed release of a core drug DOX. In tumor bearing mice intravenously administered NPs were found to accumulate at the tumor site by fluorescence imaging.

Doxorubicin loaded superparamagnetic PLGA-iron oxide multifunctional microbubbles for dual-mode US/MR imaging and therapy of metastasis in lymph nodes.

PubMed

Niu, Chengcheng; Wang, Zhigang; Lu, Guangming; Krupka, Tianyi M; Sun, Yang; You, Yufang; Song, Weixiang; Ran, Haitao; Li, Pan; Zheng, Yuanyi

2013-03-01

Current strategies for tumor-induced sentinel lymph node detection and metastasis therapy have limitations. In this work, we co-encapsulated iron oxide nanoparticles and chemotherapeutic drug into poly(lactic-co-glycolic acid) (PLGA) microbubbles to form multifunctional polymer microbubbles (MPMBs) for both tumor lymph node imaging and therapy. Fe(3)O(4) nanoparticles and doxorubicin (DOX) co-encapsulated PLGA microbubbles were prepared and filled with perfluorocarbon gas. Enhancement of ultrasound (US)/magnetic resonance (MR) imaging and US triggered drug delivery were evaluated both in vitro and in vivo. The MPMBs exhibited characters like narrow size distribution and smooth surface with a mean diameter of 868.0 ± 68.73 nm. In addition, varying the concentration of Fe(3)O(4) nanoparticles in the bubbles did not significantly influence the DOX encapsulation efficiency or drug loading efficiency. Our in vitro results demonstrated that these MPMBs could enhance both US and MR imaging which was further validated in vivo showing that these MPMBs enhanced tumor lymph nodes signals. The anti-tumor effect of MPMBs mediated chemotherapy was assessed in vivo using end markers like tumor proliferation index, micro blood vessel density and micro lymphatic vessel density, which were shown consistently the lowest after the MPMBs plus sonication treatment compared to controls. In line with these findings, the tumor cell apoptotic index was found the largest after the MPMBs plus sonication treatment. In conclusion, we have successfully developed a doxorubicin loaded superparamagnetic PLGA-Iron Oxide multifunctional theranostic agent for dual-mode US/MR Imaging of lymph node, and for low frequency US triggered therapy of metastasis in lymph nodes, which might provide a strategy for the imaging and chemotherapy of primary tumor and their metastases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Use of fibrin sealants for the localized, controlled release of cefazolin

PubMed Central

Tredwell, Stephen; Jackson, John K.; Hamilton, Donald; Lee, Vivian; Burt, Helen M.

2006-01-01

Background Fibrin sealants are used increasingly in surgery to reduce bleeding and improve wound healing. They have great potential as biocompatible, biodegradable drug delivery systems, because the sealant may adhere to the target tissue and allow controlled release of the drug over an extended period. We investigated the encapsulation, stability and controlled release of erythromycin and cefazolin from Beriplast fibrin sealants (Aventis Behring Canada). Methods Drug-loaded clots were cast in glass vials and allowed to set. We observed the clots for drug precipitation and aggregation, and we assessed the effect of drug encapsulation on clot strength. Drug stability and release from the clots in phosphate buffered saline (PBS) was quantified by ultraviolet and visible violet absorbance spectroscopy and high-performance liquid chromatography. Results Erythromycin was found to release slowly from the fibrin clots over the first 2 hours but then degrade rapidly. Cefazolin was found to be very stable in clots in PBS (97% stable at 2 d and 93% stable at 5 d). The drug released in a controlled manner over 2 days, with most being released during the first day. The dose of drug released could be varied by changing the amount placed in the thrombin solution. Clot thickness had no effect on the rate of cefazolin release. Conclusion Overall, the 2-day release profile and the excellent stability of the drug suggest that cefazolin-loaded fibrin sealants may offer an effective route of postoperative antibiotic delivery. PMID:17152573

Stability of hepatoprotecting agent IFC-305 encapsulated into sol-gel titania nanoparticles and drug release evaluation: water and drug concentration effect.

PubMed

Albarran, L; López, T; Quintana, P; Chagoya, V

2012-03-01

IFC-305 was encapsulated into nanostructured titania and functionalized with OH groups by the sol-gel process using titanium n-butoxide, to be used in a drug delivery system for the treatment of liver cancer. Synthesis was carried out at different molar hydrolysis ratios: 4, 8, 16 and 24 mol of water; and drug concentration of 10, 20 and 30%. Characterization of IFC-titania reservoirs was carried out by Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermal analysis (DTA-TGA), scanning electron microscopy (SEM), and N2 adsorption-desorption isotherms (BET), confirms that IFC-305 is entrapped and stabilized in the TiO2-OH matrix. Drug liberation in vitro was determined by UV spectrometry over a period of 1000 h. This study demonstrated that the higher water content and the higher amount of loaded IFC, favored hydrogen bonding between titania-OH surface and IFC-NH groups, increasing the rate of drug release.

Fabrication of Polymeric Micelles with Aggregation-Induced Emission and Forster Resonance Energy Transfer for Anticancer Drug Delivery.

PubMed

Hao, Na; Sun, Changzhen; Wu, Zhengfei; Xu, Long; Gao, Wenxia; Cao, Jun; Li, Li; He, Bin

2017-07-19

With the aim of obtaining effective cancer therapy with simultaneous cellular imaging, dynamic drug-release monitoring, and chemotherapeutic treatment, a polymeric micelle with aggregation-induced emission (AIE) imaging and a Forster resonance energy transfer (FRET) effect was fabricated as the drug carrier. An amphiphilic conjugate of 1H-pyrrole-1-propanoicacid (MAL)-poly(ethylene glycol) (PEG)-Tripp-bearing AIE molecules were synthesized and self-assembled into micelles to load the anticancer drug doxorubicin (DOX). Spherical DOX-loaded micelles with the mean size of 106 nm were obtained with good physiological stability (CMC, 12.5 μg/mL), high drug-loading capacity (10.4%), and encapsulation efficiency (86%). The cellular uptake behavior of DOX-loaded MAL-PEG-Tripp micelles was visible for high-quality intracellular imaging due to the AIE property. The delivery of DOX from the drug-loaded micelles was dynamic monitored by the FRET effect between the DOX and MAL-PEG-Tripp. Both in vitro (IC50, 2.36 μg/mL) and in vivo anticancer activity tests revealed that the DOX-loaded MAL-PEG-Tripp micelles exhibited promising therapeutic efficacy to cancer with low systematic toxicity. In summary, this micelle provided an effective way to fabricate novel nanoplatform for intracellular imaging, drug-delivery tracing, and chemotherapy.

Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells

PubMed Central

Li, Xian; Li, Hao; Yi, Wei; Chen, Jianyu; Liang, Biling

2013-01-01

Purpose To research the acid-triggered core cross-linked folate-poly(ethylene glycol)-b-poly[N-(N′,N′-diisopropylaminoethyl) glutamine] (folated-PEG-P[GA-DIP]) amphiphilic block copolymer for targeted drug delivery and magnetic resonance imaging (MRI) in liver cancer cells. Methods As an appropriate receptor of protons, the N,N-diisopropyl tertiary amine group (DIP) was chosen to conjugate with the side carboxyl groups of poly(ethylene glycol)-b-poly (L-glutamic acid) to obtain PEG-P(GA-DIP) amphiphilic block copolymers. By ultrasonic emulsification, PEG-P(GA-DIP) could be self-assembled to form nanosized micelles loading doxorubicin (DOX) and superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution. When PEG-P(GA-DIP) nanomicelles were combined with folic acid, the targeted effect of folated-PEG-P(GA-DIP) nanomicelles was evident in the fluorescence and MRI results. Results To further increase the loading efficiency and the cell-uptake of encapsulated drugs (DOX and SPIONs), DIP (pKa≈6.3) groups were linked with ~50% of the side carboxyl groups of poly(L-glutamic acid) (PGA), to generate the core cross-linking under neutral or weakly acidic conditions. Under the acidic condition (eg, endosome/lysosome), the carboxyl groups were neutralized to facilitate disassembly of the P(GA-DIP) blocks’ cross-linking, for duly accelerating the encapsulated drug release. Combined with the tumor-targeting effect of folic acid, specific drug delivery to the liver cancer cells and MRI diagnosis of these cells were greatly enhanced. Conclusion Acid-triggered and folate-decorated nanomicelles encapsulating SPIONs and DOX, facilitate the targeted MRI diagnosis and therapeutic effects in tumors. PMID:23976852

Aqueous-core PEG-coated PLA nanocapsules for an efficient entrapment of water soluble anticancer drugs and a smart therapeutic response.

PubMed

Cosco, Donato; Paolino, Donatella; De Angelis, Francesco; Cilurzo, Felisa; Celia, Christian; Di Marzio, Luisa; Russo, Diego; Tsapis, Nicolas; Fattal, Elias; Fresta, Massimo

2015-01-01

Novel PEGylated PLA nanocapsules (PEG-AcPLA nanocapsules), loading high percentage of water soluble drugs have been formulated by using multiple emulsion technique without using conventional stabilizers. In particular, sodium deoxycholate hydrate has been used to obtain nanocapsules having a mean diameter of about 200 nm and a polydispersity index of ∼ 0.1. Gemcitabine hydrochloride (GEM) was used as a model of hydrophilic drug. GEM-loaded PEG-AcPLA nanocapsules demonstrated a high encapsulation efficacy and the drug-release followed a zero-order kinetic. MTT-assay evidenced an increased antitumor effect of GEM-loaded PEG-AcPLA nanocapsules compared to the free drug on different cancer cell lines and confocal laser scanning microscopy showed a significant improvement of cell interaction at 6h of incubation. In vivo anticancer activity of GEM-loaded PEG-AcPLA nanocapsules using two xenograft murine models of human solid tumors further supported the efficacy of this nano-drug, thus providing preliminary results about the potential clinical application of this innovative nanotherapeutic. Copyright © 2014 Elsevier B.V. All rights reserved.

Predicting drug loading in PLA-PEG nanoparticles.

PubMed

Meunier, M; Goupil, A; Lienard, P

2017-06-30

Polymer nanoparticles present advantageous physical and biopharmaceutical properties as drug delivery systems compared to conventional liquid formulations. Active pharmaceutical ingredients (APIs) are often hydrophobic, thus not soluble in conventional liquid delivery. Encapsulating the drugs in polymer nanoparticles can improve their pharmacological and bio-distribution properties, preventing rapid clearance from the bloodstream. Such nanoparticles are commonly made of non-toxic amphiphilic self-assembling block copolymers where the core (poly-[d,l-lactic acid] or PLA) serves as a reservoir for the API and the external part (Poly-(Ethylene-Glycol) or PEG) serves as a stealth corona to avoid capture by macrophage. The present study aims to predict the drug affinity for PLA-PEG nanoparticles and their effective drug loading using in silico tools in order to virtually screen potential drugs for non-covalent encapsulation applications. To that end, different simulation methods such as molecular dynamics and Monte-Carlo have been used to estimate the binding of actives on model polymer surfaces. Initially, the methods and models are validated against a series of pigments molecules for which experimental data exist. The drug affinity for the core of the nanoparticles is estimated using a Monte-Carlo "docking" method. Drug miscibility in the polymer matrix, using the Hildebrand solubility parameter (δ), and the solvation free energy of the drug in the PLA polymer model is then estimated. Finally, existing published ALogP quantitative structure-property relationships (QSPR) are compared to this method. Our results demonstrate that adsorption energies modelled by docking atomistic simulations on PLA surfaces correlate well with experimental drug loadings, whereas simpler approaches based on Hildebrand solubility parameters and Flory-Huggins interaction parameters do not. More complex molecular dynamics techniques which use estimation of the solvation free energies both in PLA and in water led to satisfactory predictive models. In addition, experimental drug loadings and Log P are found to correlate well. This work can be used to improve the understanding of drug-polymer interactions, a key component to designing better delivery systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and evaluation of a novel drug delivery: Soluplus®/TPGS mixed micelles loaded with piperine in vitro and in vivo.

PubMed

Ding, Yingying; Wang, Changyuan; Wang, Yutong; Xu, Youwei; Zhao, Jing; Gao, Meng; Ding, Yanfang; Peng, Jinyong; Li, Lei

2018-05-27

Although piperine can inhibit cells of tumors, the poor water solubility restricted its clinical application. This paper aimed to develop mixed micelles based on Soluplus ® and D-α-tocopherol polyethylene glycol succinate (TPGS) to improve the aqueous solubility and anti-cancer effect. Piperine-loaded mixed micelles were prepared using a thin-film hydration method, and their physicochemical properties were characterized. The cellular uptake of the micelles was confirmed by confocal laser scanning microscopy in A549 lung cancer cells and HepG 2 liver cancer cells. In addition, cytotoxicity of the piperine mixed micelles was studied in A549 lung cancer cells and HepG 2 liver cancer cells. Free piperine or piperine-loaded Soluplus ® /TPGS mixed micelles were administered at an equivalent dose of piperine at 3.2 mg/kg via a single intravenous injection in the tail vain for the pharmacokinetic study in vivo. The diameter of piperine-loaded Soluplus ® /TPGS (4:1) mixed micelles was about 61.9 nm and the zeta potential -1.16 ± 1.06 mV with 90.9% of drug encapsulation efficiency and 4.67% of drug-loading efficiency. Differential scanning calorimetry (DSC) studies confirmed that piperine is encapsulated by the Soluplus ® /TPGS. The release results in vitro showed that the piperine-loaded Soluplus ® /TPGS mixed micelles presented sustained release behavior compared to the free piperine. The mixed micelles exhibited better antitumor efficacy compared to free piperine and physical mixture against in A549 and HepG 2 cells by MTT assay. The pharmacokinetic study revealed that the AUC of piperine-loaded mixed micelles was 2.56 times higher than that of piperine and the MRT for piperine-loaded mixed micelles was 1.2-fold higher than piperine (p < .05). The results of the study suggested that the piperine-loaded mixed micelles developed might be a potential nano-drug delivery system for cancer chemotherapy. These results demonstrated that piperine-loaded Soluplus ® /TPGS mixed micelles are an effective strategy to deliver piperine for cancer therapy.

A multifunctional biphasic suspension of mesoporous silica encapsulated with YVO4:Eu3+ and Fe3O4 nanoparticles: synergistic effect towards cancer therapy and imaging.

PubMed

Shanta Singh, N; Kulkarni, Hrishikesh; Pradhan, Lina; Bahadur, D

2013-02-15

Polyol mediated synthesized luminescent YVO(4):Eu(3+) nanoparticles (NPs) have been encapsulated in mesoporous silica nanoparticles (MSNs) using the sol-gel process. X-ray diffraction and Fourier transform infrared spectroscopy along with transmission electron microscopy confirm the encapsulation of the YVO(4):Eu(3+) NPs in the SiO(2) matrix. N(2) adsorption/desorption analysis confirms the mesoporous nature of the MSNs and YVO(4):Eu(3+)-MSNs. No significant quenching of the YVO(4):Eu(3+) luminescence is observed for YVO(4):Eu(3+)-MSNs. This nanocomposite has been tested as a potential drug carrier. Efficient loading of doxorubicin hydrochloride (DOX), a typical anticancer drug, is observed which reaches up to 93% in 8 mg ml(-1) of YVO(4):Eu(3+)-MSNs. pH sensitive release of DOX is observed, with 54% release for pH 4.3 and 31% in a physiological environment (pH 7.4). Both MSNs and YVO(4):Eu(3+)-MSNs nanocomposites do not show accountable toxicity to two cell lines, i.e. HeLa and MCF-7. However, as desired, toxicity is observed when cells are incubated with DOX loaded YVO(4):Eu(3+)-MSNs. Laser scanning confocal microscopy images confirm the uptake of the nanocomposite in both cell lines. The morphology of the cells (MCF-7) changes after incubation with DOX loaded YVO(4):Eu(3+)-MSNs, indicating an interaction of DOX with the cells. More cytotoxicity to both cell lines with ∼90% killing is observed due to the synergistic effect of magnetic fluid hyperthermia and chemotherapy using a biphasic suspension of superparamagnetic iron oxide magnetic nanoparticles and DOX loaded YVO(4):Eu(3+)-MSNs. In addition, an AC magnetic field triggers an enhanced drug release.

Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

PubMed Central

Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

2014-01-01

To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells. PMID:24591829

Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells.

PubMed

Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

2014-01-01

To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.

Formulation, optimization and evaluation of curcumin-β-cyclodextrin-loaded sponge for effective drug delivery in thermal burns chemotherapy.

PubMed

Kaur, Navdeep; Garg, Tarun; Goyal, Amit K; Rath, Goutam

2016-09-01

The present study was designed to determine the role of curcumin-β-cyclodextrin-loaded sponge on burn wound healing in rats. Curcumin-β-cyclodextrin complex was prepared by the solvent evaporation encapsulation method. Molecular inclusion complex of curcumin-β-cyclodextrin was incorporated into gelatin sponge. The developed sponge was characterized for drug entrapment, drug release and morphology. The biological activity of optimized formulation was determined on burn wounds which were made on rats. The burn wound healing efficacy was analyzed through physical and histological changes observed at the wound sites. There was a significant decrease in rate of wound contraction in experimental groups then the control group. Curcumin-β-cyclodextrin-loaded sponge treated wound was found to heal in rate comparable to marketed formulation with no sign of adverse consequence. The result clearly substantiates the beneficial effects of curcumin-β-cyclodextrin-loaded sponge in the acceleration of wound healing.

Micro-Encapsulated Porphyrins and Phthalocyanines - New Formulations in Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Ion, R. M.

2017-06-01

Photodynamic therapy (PDT), as an innovative method for cancer tretament is based on a concerted action of some drugs, called sensitizers, which generate reactive oxygen species via a photochemical mechanism, leading to cellular necrosis or apoptosis. The present work aims at loading some sensitizers, as porphyrins (P) and phthalocyanines (Pc) into alginate particles. Particles were prepared by dropping alginate into an aqueous solution containing P or Pc and CaCl2, which allows the formation of particles through ionic crosslinking. It was obtained P or Pc loaded alginate beads with an average diameter of about 100 μm. For these systems, this paper analyses the spectroscopic properties, encapsulation into microcapsules, controlled releasing action and their photosensitizer capacity (singlet oxygen generation).

Synthesis, characterization and in vitro studies of doxorubicin-loaded magnetic nanoparticles grafted to smart copolymers on A549 lung cancer cell line.

PubMed

Akbarzadeh, Abolfazl; Samiei, Mohammad; Joo, Sang Woo; Anzaby, Maryam; Hanifehpour, Younes; Nasrabadi, Hamid Tayefi; Davaran, Soodabeh

2012-12-18

The aim of present study was to develop the novel methods for chemical and physical modification of superparamagnetic iron oxide nanoparticles (SPIONs) with polymers via covalent bonding entrapment. These modified SPIONs were used for encapsulation of anticancer drug doxorubicin. At first approach silane-grafted magnetic nanoparticles was prepared and used as a template for polymerization of the N-isopropylacrylamide (NIPAAm) and methacrylic acid (MAA) via radical polymerization. This temperature/pH-sensitive copolymer was used for preparation of DOX-loaded magnetic nanocomposites. At second approach Vinyltriethoxysilane-grafted magnetic nanoparticles were used as a template to polymerize PNIPAAm-MAA in 1, 4 dioxan and methylene-bis-acrylamide (BIS) was used as a cross-linking agent. Chemical composition and magnetic properties of Dox-loaded magnetic hydrogel nanocomposites were analyzed by FT-IR, XRD, and VSM. The results demonstrate the feasibility of drug encapsulation of the magnetic nanoparticles with NIPAAm-MAA copolymer via covalent bonding. The key factors for the successful prepardtion of magnetic nanocomposites were the structure of copolymer (linear or cross-linked), concentration of copolymer and concentration of drug. The influence of pH and temperature on the release profile of doxorubicin was examined. The in vitro cytotoxicity test (MTT assay) of both magnetic DOx-loaded nanoparticles was examined. The in vitro tests showed that these systems are no toxicity and are biocompatible. IC50 of DOx-loaded Fe3O4 nanoparticles on A549 lung cancer cell line showed that systems could be useful in treatment of lung cancer.

Disulfiram-loaded mixed nanoparticles with high drug-loading and plasma stability by reducing the core crystallinity for intravenous delivery.

PubMed

Zhuo, Xuezhi; Lei, Tian; Miao, Linlin; Chu, Wei; Li, Xiaowen; Luo, Lifeng; Gou, Jingxin; Zhang, Yu; Yin, Tian; He, Haibing; Tang, Xing

2018-05-30

To develop an injectable formulation and improve the stability of disulfiram (DSF), DSF was encapsulated into mixed nanoparticles (DSF-NPs) through a high-pressure homogenization method. The Flory-Huggins interaction parameters (χ FH ) were calculated to predict the miscibility between DSF and the hydrophobic core, resulting in PCL 5000 selected as the hydrophobic block to encapsulate the DSF, as PCL 5000 had a lower χ FH 3.39 and the drug loading of the nanoparticles prepared by mPEG 5000 -PCL 5000 was relatively higher. mPEG 5000 -PCL 5000 and PCL 5000 were blended to reduce the leakage of DSF during preparation, as well as increase the stability of the nanoparticles. The cargo-loading capacity of the nanoparticles was improved from 3.35% to 5.50% by reducing the crystallinity of the PCL nanoparticle core, and the crystallinity decreased from 51.13% to 25.15% after adding medium chain triglyceride (MCT). The DSF-NPs prepared by the above method had a small particle size of 98.1 ± 10.54 nm, with a polydispersity index (PDI) of 0.036, as well as drug loading of 5.50%. Furthermore, DSF-NPs containing MCT showed higher stability than DSF-NPs without MCT and DSF-sol (DSF dissolved in Cremophor EL and ethanol) in water and 90% plasma-containing PBS. The pharmacokinetics proved that DSF-NPs containing MCT enhanced the DSF concentration in the blood. Finally, DSF-NPs effectively inhibited H22 xenograft tumor growth in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

Glucose-Responsive Supramolecular Vesicles Based on Water-Soluble Pillar[5]arene and Pyridylboronic Acid Derivatives for Controlled Insulin Delivery.

PubMed

Gao, Lei; Wang, Tingting; Jia, Keke; Wu, Xuan; Yao, Chenhao; Shao, Wei; Zhang, Dongmei; Hu, Xiao-Yu; Wang, Leyong

2017-05-11

The stimuli-responsive behavior of supramolecular nanocarriers is crucial for their potential applications as smart drug delivery systems. We hereby constructed a glucose-responsive supramolecular drug delivery system based on the host-guest interaction between a water-soluble pillar[5]arene (WP5) and a pyridylboronic acid derivative (G) for insulin delivery and controlled release under physiological conditions. The approach represents the ideal treatment of diabetes mellitus. The drug loading and in vitro drug release experiments demonstrated that large molecular weight insulin could be encapsulated into the vesicles with high loading efficiency, which, to our knowledge, is the first example of small-size supramolecular vesicles with excellent encapsulation capacity of a large protein molecule. Moreover, FITC-labeled insulin was used to evaluate the release behavior of insulin, and it was demonstrated that high glucose concentration could facilitate the quick release of insulin, suggesting a smart drug delivery system for potential application in controlled insulin release only under hyperglycemic conditions. Finally, we demonstrated that these supramolecular nanocarriers have good cytocompatibility, which is essential for their further biomedical applications. The present study provides a novel strategy for the construction of glucose-responsive smart supramolecular drug delivery systems, which has potential applications for the treatment of diabetes mellitus. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Precision spherical nucleic acids for delivery of anticancer drugs† †Electronic supplementary information (ESI) available: DNA nanoparticle design and assembly, evaluation of BKM120 encapsulation, structural characterization, stability and shelf-life of drug-loaded structures, cellular uptake in cancer cells, in vitro cell studies, HSA binding experiments and in vivo studies. See DOI: 10.1039/c7sc01619k Click here for additional data file. Click here for additional data file. Click here for additional data file.

PubMed Central

Bousmail, Danny; Amrein, Lilian; Fakhoury, Johans J.; Fakih, Hassan H.; Hsu, John C. C.

2017-01-01

We report a spherical nucleic acid (SNA) system for the delivery of BKM120, an anticancer drug for treatment of chronic lymphocytic leukemia (CLL). While promising for cancer treatment, this drug crosses the blood–brain barrier causing significant side-effects in patients. The DNA nanoparticle encapsulates BKM120 in high efficiency, and is unparalleled in its monodispersity, ease of synthesis and stability in different biological media and in serum. These DNA nanostructures demonstrate efficient uptake in human cervical cancer (HeLa) cells, and increased internalization of cargo. In vitro studies show that BKM120-loaded nanoparticles promote apoptosis in primary patient CLL lymphocytes, and act as sensitizers of other antitumor drugs, without causing non-specific inflammation. Evaluation of this drug delivery system in vivo shows long circulation times up to 24 hours, full body distribution, accumulation at tumor sites and minimal leakage through the blood–brain barrier. Our results demonstrate the great potential of these delivery vehicles as a general platform for chemotherapeutic drug delivery. PMID:28989655

Hydrophobically modified glycol chitosan nanoparticles-encapsulated camptothecin enhance the drug stability and tumor targeting in cancer therapy.

PubMed

Min, Kyung Hyun; Park, Kyeongsoon; Kim, Yoo-Shin; Bae, Sang Mun; Lee, Seulki; Jo, Hyung Gon; Park, Rang-Woon; Kim, In-San; Jeong, Seo Young; Kim, Kwangmeyung; Kwon, Ick Chan

2008-05-08

To prepare a water-insoluble camptothecin (CPT) delivery carrier, hydrophobically modified glycol chitosan (HGC) nanoparticles were constructed by chemical conjugation of hydrophobic 5beta-cholanic acid moieties to the hydrophilic glycol chitosan backbone. Insoluble anticancer drug, CPT, was easily encapsulated into HGC nanoparticles by a dialysis method and the drug loading efficiency was above 80%. CPT-encapsulated HGC (CPT-HGC) nanoparticles formed nano-sized self-aggregates in aqueous media (280-330 nm in diameter) and showed sustained release of CPT for 1 week. Also, HGC nanoparticles effectively protected the active lactone ring of CPT from the hydrolysis under physiological condition, due to the encapsulation of CPT into the hydrophobic cores in the HGC nanoparticles. The CPT-HGC nanoparticles exhibited significant antitumor effects and high tumor targeting ability towards MDA-MB231 human breast cancer xenografts subcutaneously implanted in nude mice. Tumor growth was significantly inhibited after i.v. injection of CPT-HGC nanoparticles at doses of 10 mg/kg and 30 mg/kg, compared to free CPT at dose of 30 mg/kg. The significant antitumor efficacy of CPT-HGC nanoparticles was attributed to the ability of the nanoparticles to show both prolonged blood circulation and high accumulation in tumors, as confirmed by near infrared (NIR) fluorescence imaging systems. Thus, the delivery of CPT to tumor tissues at a high concentration, with the assistance of HGC nanoparticles, exerted a potent therapeutic effect. These results reveal the promising potential of HGC nanoparticles-encapsulated CPT as a stable and effective drug delivery system in cancer therapy.

Development and characterisation of chitosan films impregnated with insulin loaded PEG-b-PLA nanoparticles (NPs): a potential approach for buccal delivery of macromolecules.

PubMed

Giovino, Concetta; Ayensu, Isaac; Tetteh, John; Boateng, Joshua S

2012-05-30

Mucoadhesive chitosan based films, incorporated with insulin loaded nanoparticles (NPs) made of poly(ethylene glycol)methyl ether-block-polylactide (PEG-b-PLA) have been developed and characterised. Blank-NPs were prepared by double emulsion solvent evaporation technique with varying concentrations of the copolymer (5 and 10%, w/v). The optimised formulation was loaded with insulin (model protein) at initial loadings of 2, 5 and 10% with respect to copolymer weight. The developed NPs were analysed for size, size distribution, surface charge, morphology, encapsulation efficiency and drug release. NPs showing negative (ζ)-potential (<-6 mV) with average diameter> 300 nm and a polydispersity index (P.I.) of ≈ 0.2, irrespective of formulation process, were achieved. Insulin encapsulation efficiencies of 70% and 30% for NPs-Insulin-2 and NPs-Insulin-5 were obtained, respectively. The in vitro release behaviour of both formulations showed a classic biphasic sustained release of protein over 5 weeks which was influenced by pH of the release medium. Optimised chitosan films embedded with 3mg of insulin loaded NPs were produced by solvent casting with homogeneous distribution of NPs in the mucoadhesive matrix, which displayed excellent physico-mechanical properties. The drug delivery system has been designed as a novel platform for potential buccal delivery of macromolecules. Copyright © 2012 Elsevier B.V. All rights reserved.

Biodegradable thermoresponsive polymeric magnetic nanoparticles: a new drug delivery platform for doxorubicin

NASA Astrophysics Data System (ADS)

Andhariya, Nidhi; Chudasama, Bhupendra; Mehta, R. V.; Upadhyay, R. V.

2011-04-01

The use of nanoparticles as drug delivery systems for anticancer therapeutics has great potential to revolutionize the future of cancer therapy. The aim of this study is to construct a novel drug delivery platform comprising a magnetic core and biodegradable thermoresponsive shell of tri-block-copolymer. Oleic acid-coated Fe3O4 nanoparticles and hydrophilic anticancer drug "doxorubicin" are encapsulated with PEO-PLGA-PEO (polyethylene oxide-poly d, l lactide-co-glycolide-polyethylene oxide) tri-block-copolymer. Structural, magnetic, and physical properties of Fe3O4 core are determined by X-ray diffraction, vibrating sample magnetometer, and transmission electron microscopy techniques, respectively. The hydrodynamic size of composite nanoparticles is determined by dynamic light scattering and is found to be 36.4 nm at 25 °C. The functionalization of magnetic core with various polymeric chain molecules and their weight proportions are determined by Fourier transform infrared spectroscopy and thermogravimetric analysis, respectively. Encapsulation of doxorubicin into the polymeric magnetic nanoparticles, its loading efficiency, and kinetics of drug release are investigated by UV-vis spectroscopy. The loading efficiency of drug is 89% with a rapid release for the initial 7 h followed by the sustained release over a period of 36 h. The release of drug is envisaged to occur in response to the physiological temperature by deswelling of thermoresponsive PEO-PLGA-PEO block-copolymer. This study demonstrates that temperature can be exploited successfully as an external parameter to control the release of drug.

Micelle-templated, poly(lactic-co-glycolic acid) nanoparticles for hydrophobic drug delivery.

PubMed

Nabar, Gauri M; Mahajan, Kalpesh D; Calhoun, Mark A; Duong, Anthony D; Souva, Matthew S; Xu, Jihong; Czeisler, Catherine; Puduvalli, Vinay K; Otero, José Javier; Wyslouzil, Barbara E; Winter, Jessica O

2018-01-01

Poly(lactic- co -glycolic acid) (PLGA) is widely used for drug delivery because of its biocompatibility, ability to solubilize a wide variety of drugs, and tunable degradation. However, achieving sub-100 nm nanoparticles (NPs), as might be desired for delivery via the enhanced permeability and retention effect, is extremely difficult via typical top-down emulsion approaches. Here, we present a bottom-up synthesis method yielding PLGA/block copolymer hybrids (ie, "PolyDots"), consisting of hydrophobic PLGA chains entrapped within self-assembling poly(styrene- b -ethylene oxide) (PS- b -PEO) micelles. PolyDots exhibit average diameters <50 nm and lower polydispersity than conventional PLGA NPs. Drug encapsulation efficiencies of PolyDots match conventional PLGA NPs (ie, ~30%) and are greater than those obtained from PS- b -PEO micelles (ie, ~7%). Increasing the PLGA:PS- b -PEO weight ratio alters the drug release mechanism from chain relaxation to erosion controlled. PolyDots are taken up by model glioma cells via endocytotic mechanisms within 24 hours, providing a potential means for delivery to cytoplasm. PolyDots can be lyophilized with minimal change in morphology and encapsulant functionality, and can be produced at scale using electrospray. Encapsulation of PLGA within micelles provides a bottom-up route for the synthesis of sub-100 nm PLGA-based nanocarriers with enhanced stability and drug-loading capacity, and tunable drug release, suitable for potential clinical applications.

Development of nanostructured lipid carrier for dacarbazine delivery

NASA Astrophysics Data System (ADS)

Almousallam, Musallam; Moia, Claudia; Zhu, Huijun

2015-09-01

Dacarbazine (Dac) is one of the most commonly used chemotherapy drugs for treating various cancers. However, its poor water solubility, short half-life in blood circulation, low response rate and high side effect limit its application. This study aimed to improve the drug solubility and prolong drug release by developing nanostructured lipid carriers (NLCs) for Dac delivery. The NLC and Dac-encapsulated NLC were synthesized with precirol ATO 5 and isopropyl myristate as lipids, tocopheryl polyethylene glycol succinate, soybean lecithin and Kolliphor P 188 as co-surfactants. The NLCs with controlled size were achieved using high shear dispersion following solidification of oil-in-water emulsion. For Dac encapsulation, the smallest NLC with 155 ± 10 nm in size, 0.2 ± 0.01 polydispersion index and -43.4 ± 2 mV zeta potential was selected. The resultant DLC-Dac possessed size, polydispersion index and zeta potential of 190 ± 10, 0.2 ± 0.01, and -43.5 ± 1.2, respectively. The drug encapsulation efficiency and drug loading were 98.5 % and 14 %, respectively. In vitro drug release study showed a biphasic pattern, with 50 % released in the first 2 h, and the remaining released sustainably for up to 30 h. This is the first report on the development of NLC for Dac delivery, implying that NLC could be a new potential candidate as drug carrier to improve the therapeutic profile of Dac.

Micelle-templated, poly(lactic-co-glycolic acid) nanoparticles for hydrophobic drug delivery

PubMed Central

Nabar, Gauri M; Mahajan, Kalpesh D; Calhoun, Mark A; Duong, Anthony D; Souva, Matthew S; Xu, Jihong; Czeisler, Catherine; Puduvalli, Vinay K; Otero, José Javier; Wyslouzil, Barbara E; Winter, Jessica O

2018-01-01

Purpose Poly(lactic-co-glycolic acid) (PLGA) is widely used for drug delivery because of its biocompatibility, ability to solubilize a wide variety of drugs, and tunable degradation. However, achieving sub-100 nm nanoparticles (NPs), as might be desired for delivery via the enhanced permeability and retention effect, is extremely difficult via typical top-down emulsion approaches. Methods Here, we present a bottom-up synthesis method yielding PLGA/block copolymer hybrids (ie, “PolyDots”), consisting of hydrophobic PLGA chains entrapped within self-assembling poly(styrene-b-ethylene oxide) (PS-b-PEO) micelles. Results PolyDots exhibit average diameters <50 nm and lower polydispersity than conventional PLGA NPs. Drug encapsulation efficiencies of PolyDots match conventional PLGA NPs (ie, ~30%) and are greater than those obtained from PS-b-PEO micelles (ie, ~7%). Increasing the PLGA:PS-b-PEO weight ratio alters the drug release mechanism from chain relaxation to erosion controlled. PolyDots are taken up by model glioma cells via endocytotic mechanisms within 24 hours, providing a potential means for delivery to cytoplasm. PolyDots can be lyophilized with minimal change in morphology and encapsulant functionality, and can be produced at scale using electrospray. Conclusion Encapsulation of PLGA within micelles provides a bottom-up route for the synthesis of sub-100 nm PLGA-based nanocarriers with enhanced stability and drug-loading capacity, and tunable drug release, suitable for potential clinical applications. PMID:29391794

Liposomes Size Engineering by Combination of Ethanol Injection and Supercritical Processing.

PubMed

Santo, Islane Espirito; Campardelli, Roberta; Albuquerque, Elaine Cabral; Vieira De Melo, Silvio A B; Reverchon, Ernesto; Della Porta, Giovanna

2015-11-01

Supercritical fluid extraction using a high-pressure packed tower is proposed not only to remove the ethanol residue from liposome suspensions but also to affect their size and distribution leading the production of nanosomes. Different operating pressures, temperatures, and gas to liquid ratios were explored and ethanol was successfully extracted up to a value of 400 ppm; liposome size and distribution were also reduced by the supercritical processing preserving their integrity, as confirmed by Z-potential data and Trasmission Electron Microscopy observations. Operating at 120 bar and 38°C, nanosomes with a mean diameter of about 180 ± 40 nm and good storage stability were obtained. The supercritical processing did not interfere on drug encapsulation, and no loss of entrapped drug was observed when the water-soluble fluorescein was loaded as a model compound. Fluorescein encapsulation efficiency was 30% if pure water was used during the supercritical extraction as processing fluid; whereas an encapsulation efficiency of 90% was obtained if the liposome suspension was processed in water/fluorescein solution. The described technology is easy to scale up to an industrial production and merge in one step the solvent extraction, liposome size engineering, and an excellent drug encapsulation in a single operation unit. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel system.

PubMed

Giray, Seda; Bal, Tuğba; Kartal, Ayse M; Kızılel, Seda; Erkey, Can

2012-05-01

A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drug delivery system was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications. Copyright © 2012 Wiley Periodicals, Inc.

Enhanced intracellular delivery and antibacterial efficacy of enrofloxacin-loaded docosanoic acid solid lipid nanoparticles against intracellular Salmonella.

PubMed

Xie, Shuyu; Yang, Fei; Tao, Yanfei; Chen, Dongmei; Qu, Wei; Huang, Lingli; Liu, Zhenli; Pan, Yuanhu; Yuan, Zonghui

2017-01-23

Enrofloxacin-loaded docosanoic acid solid lipid nanoparticles (SLNs) with different physicochemical properties were developed to enhance activity against intracellular Salmonella. Their cellular uptake, intracellular elimination and antibacterial activity were studied in RAW 264.7 cells. During the experimental period, SLN-encapsulated enrofloxacin accumulated in the cells approximately 27.06-37.71 times more efficiently than free drugs at the same extracellular concentration. After incubation for 0.5 h, the intracellular enrofloxacin was enhanced from 0.336 to 1.147 μg/mg of protein as the sizes of nanoparticles were increased from 150 to 605 nm, and from 0.960 to 1.147 μg/mg of protein when the charge was improved from -8.1 to -24.9 mv. The cellular uptake was more significantly influenced by the size than it was by the charge, and was not affected by whether the charge was positive or negative. The elimination of optimal SLN-encapsulated enrofloxacin from the cells was significantly slower than that of free enrofloxacin after removing extracellular drug. The inhibition effect against intracellular Salmonella CVCC541 of 0.24 and 0.06 μg/mL encapsulated enrofloxacin was stronger than 0.6 μg/mL free drug after all of the incubation periods and at 48 h, respectively. Docosanoic acid SLNs are thus considered as a promising carrier for intracellular bacterial treatment.

Dual photo- and pH-responsive supramolecular nanocarriers based on water-soluble pillar[6]arene and different azobenzene derivatives for intracellular anticancer drug delivery.

PubMed

Hu, Xiao-Yu; Jia, Keke; Cao, Yu; Li, Yan; Qin, Shan; Zhou, Fan; Lin, Chen; Zhang, Dongmei; Wang, Leyong

2015-01-12

Two novel types of supramolecular nanocarriers fabricated by the amphiphilic host-guest inclusion complex formed from water-soluble pillar[6]arene (WP6) and azobenzene derivatives G1 or G2 have been developed, in which G1 is structurally similar to G2 but has an extra phenoxy group in its hydrophobic region. Supramolecular micelles can be initially formed by WP6 with G1, which gradually transform into layered structures with liquid-crystalline properties, whereas stable supramolecular vesicles are obtained from WP6 and G2, which exhibit dual photo- and pH-responsiveness. Notably, the resulting WP6⊃G2 vesicles can efficiently encapsulate anticancer drug mitoxantrone (MTZ) to achieve MTZ-loaded vesicles, which maintain good stability in a simulated normal physiological environment, whereas in an acid environment similar to that of tumor cells or with external UV irradiation, the encapsulated drug is promptly released. More importantly, cytotoxicity assay indicates that such vesicles have good biocompatibility and the MTZ-loaded vesicles exhibit comparable anticancer activity to free MTZ, especially with additional UV stimulus, whereas its cytotoxicity for normal cells was remarkably reduced. Flow cytometric analysis further confirms that the cancer cell death caused by MTZ-loaded vesicles is associated with apoptosis. Therefore, the dual pH- and UV-responsive supramolecular vesicles are a potential platform for controlled release and targeted anticancer drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carbamazepine-loaded solid lipid nanoparticles and nanostructured lipid carriers: Physicochemical characterization and in vitro/in vivo evaluation.

PubMed

Scioli Montoto, S; Sbaraglini, M L; Talevi, A; Couyoupetrou, M; Di Ianni, M; Pesce, G O; Alvarez, V A; Bruno-Blanch, L E; Castro, G R; Ruiz, M E; Islan, G A

2018-07-01

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternatives for drug delivery to the central nervous system. In the present work, four different nanoformulations of the antiepileptic drug Carbamazepine (CBZ) were designed and prepared by the homogenization/ultrasonication method, with encapsulation efficiencies ranging from 82.8 to 93.8%. The formulations remained stable at 4 °C for at least 3 months. Physicochemical and microscopic characterization were performed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), atomic force microscopy (AFM); thermal properties by differential scanning calorimetry (DSC), thermogravimetry (TGA) and X-ray diffraction analysis (XRD). The results indicated the presence of spherical shape nanoparticles with a mean particle diameter around 160 nm in a narrow size distribution; the entrapped CBZ displayed an amorphous state. The in vitro release profile of CBZ fitted into a Baker-Lonsdale model for spherical matrices and almost the 100% of the encapsulated drug was released in a controlled manner during the first 24 h. The apparent permeability of CBZ-loaded nanoparticles through a cell monolayer model was similar to that of the free drug. In vivo experiments in a mice model of seizure suggested protection by CBZ-NLC against seizures for at least 2 h after intraperitoneal administration. The developed CBZ-loaded lipid nanocarriers displayed optimal characteristics of size, shape and drug release and possibly represent a promising tool to improve the treatment of refractory epilepsy linked to efflux transporters upregulation. Copyright © 2018 Elsevier B.V. All rights reserved.

Self-assembled stable sponge-type nanocarries for Brucea javanica oil delivery.

PubMed

Zou, Aihua; Li, Yawen; Chen, Yiyin; Angelova, Angelina; Garamus, Vasil M; Li, Na; Drechsler, Markus; Angelov, Borislav; Gong, Yabin

2017-05-01

Sponge-type nanocarriers (spongosomes) are produced upon dispersion of a liquid crystalline sponge phase formed by self-assembly of an amphiphilic lipid in excess aqueous phase. The inner organization of the spongosomes is built-up by randomly ordered bicontinuous lipid membranes and their surfaces are stabilized by alginate chains providing stealth properties and colloidal stability. The present study elaborates spongosomes for improved encapsulation of Brucea javanica oil (BJO), a traditional Chinese medicine that may strongly inhibit proliferation and metastasis of various cancers. The inner structural organization and the morphology characteristics of BJO-loaded nanocarriers at varying quantities of BJO were determined by cryogenic transmission electron microscopy (Cryo-TEM), small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). Additionally, the drug loading and drug release profiles for BJO-loaded spongosome systems also were determined. We found that the sponge-type liquid crystalline lipid membrane organization provides encapsulation efficiency rate of BJO as high as 90%. In vitro cytotoxicity and apoptosis study of BJO spongosome nanoparticles with A549 cells demonstrated enhanced anti-tumor efficiency. These results suggest potential clinical applications of the obtained safe spongosome formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergetic Effect of SLN-Curcumin and LDH-5-Fu on SMMC-7721 Liver Cancer Cell Line

PubMed Central

Zhu, Rongrong; Wu, Xianzheng; Xiao, Yu; Gao, Bo; Xie, Qian

2013-01-01

Abstract Curcumin and 5-Fluorouracil (5-Fu) have been reported to have anticancer potentials and show certain synergetic effect on some cancer cell lines. However, the poor bioavailability and rapid metabolism limited their medical application. In this study, we encapsulated curcumin with solid lipid nanoparticles (SLN), 5-Fu with Layered double hydroxides (LDHs) separately and tested its properties and anticancer potentials. SLN-curcumin and LDH-5-Fu were determined to be 100 and 60 nm by Transmission Electron Microscopy detection, and the loading efficiency were 28%±2.5% and 16.7%±1.8%, individually. Furthermore, SLN-curcumin and LDH-5-Fu showed a significantly synergetic effect on SMMC-7721 cell stronger than plain drugs together, of which the Idrug loaded nano-carriers was only 0.315. FACS analysis revealed that the combination of SLN-curcumin and LDH-5-Fu induced 80.1% apoptosis in SMMC-7721 cells, which were 1.7-folds of the sum of the two plain drug loaded carriers. The results demonstrated the significant synergetic anticancer potentials of nano-encapsulated curcumin and 5-Fu, which could be further explored for the treatment of other carcinoma. PMID:23808828

Pharmacokinetics of quercetin-loaded nanodroplets with ultrasound activation and their use for bioimaging

PubMed Central

Chang, Li-Wen; Hou, Mei-Ling; Hung, Shuo-Hui; Lin, Lie-Chwen; Tsai, Tung-Hu

2015-01-01

Bubble formulations have both diagnostic and therapeutic applications. However, research on nanobubbles/nanodroplets remains in the initial stages. In this study, a nanodroplet formulation was prepared and loaded with a novel class of chemotherapeutic drug, ie, quercetin, to observe its pharmacokinetic properties and ultrasonic bioimaging of specific sites, namely the abdominal vein and bladder. Four parallel groups were designed to investigate the effects of ultrasound and nanodroplets on the pharmacokinetics of quercetin. These groups were quercetin alone, quercetin triggered with ultrasound, quercetin-encapsulated in nanodroplets, and quercetin encapsulated in nanodroplets triggered with ultrasound. Spherical vesicles with a mean diameter of 280 nm were formed, and quercetin was completely encapsulated within. In vivo ultrasonic imaging confirmed that the nanodroplets could be treated by ultrasound. The results indicate that the initial 5-minute serum concentration, area under the concentration–time curve, elimination half-life, and clearance of quercetin were significantly enhanced by nanodroplets with or without ultrasound. PMID:25945049

Facile Fabrication of Microparticles with pH-responsive Macropores for Small Intestine Targeted Drug Formulation.

PubMed

Homayun, Bahman; Sun, Chengmeng; Kumar, Ankit; Montemagno, Carlo; Choi, Hyo-Jick

2018-05-10

Oral drugs present the most convenient, economical, and painless route for self-administration. Despite commercialization of multiple technologies relying on micro- and nanocrystalline drugs, research on microparticles (MPs) based oral biopharmaceuticals delivery systems has still not culminated well enough in commercial products. This is largely due to the drugs being exposed to the destabilizing environment during MP synthesis process, and partly because of complicated process conditions. Hence, we developed a solvent swelling-evaporation method of producing pH-responsive MPs with micron-sized macropores using poly(methacrylic acid-co-ethyl acrylate) in 1:1 ratio (commercial name: Eudragit ® L100-55 polymer). We investigated the effects of temperature and evaporation time on pore formation, freeze-drying induced pore closure, and the release profile of model drugs (fluorescent beads, lactase, and pravastatin sodium) encapsulated MPs in simulated gastrointestinal tract conditions. Encapsulated lactase/pravastatin maintained > 60% of their activity due to the preservation of pore closure, which proved the potential of this proof-of-concept microencapsulation system. Importantly, the presence of macropores on MPs can be beneficial for easy drug loading, and solve the problem of bioactivity loss during the conventional MP fabrication-drug encapsulation steps. Therefore, pH-sensing MPs with macropores can contribute to the development of oral drug formulations for a wide variety of drugs and bio-macromolecules, having a various size ranging from genes to micron-sized ingredients with high therapeutic efficacy. Copyright © 2018. Published by Elsevier B.V.

A Comparison of Aerosolization and Homogenization Techniques for Production of Alginate Microparticles for Delivery of Corticosteroids to the Colon.

PubMed

Samak, Yassmin O; El Massik, Magda; Coombes, Allan G A

2017-01-01

Alginate microparticles incorporating hydrocortisone hemisuccinate were produced by aerosolization and homogenization methods to investigate their potential for colonic drug delivery. Microparticle stabilization was achieved by CaCl 2 crosslinking solution (0.5 M and 1 M), and drug loading was accomplished by diffusion into blank microparticles or by direct encapsulation. Homogenization method produced smaller microparticles (45-50 μm), compared to aerosolization (65-90 μm). High drug loadings (40% wt/wt) were obtained for diffusion-loaded aerosolized microparticles. Aerosolized microparticles suppressed drug release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) prior to drug release in simulated colonic fluid (SCF) to a higher extent than homogenized microparticles. Microparticles prepared using aerosolization or homogenization (1 M CaCl 2 , diffusion loaded) released 5% and 17% of drug content after 2 h in SGF and 4 h in SIF, respectively, and 75% after 12 h in SCF. Thus, aerosolization and homogenization techniques show potential for producing alginate microparticles for colonic drug delivery in the treatment of inflammatory bowel disease. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Synthesis, self-assembly, and drug-loading capacity of well-defined cyclodextrin-centered drug-conjugated amphiphilic A(14)B(7) Miktoarm star copolymers based on poly(epsilon-caprolactone) and poly(ethylene glycol).

PubMed

Gou, Peng-Fei; Zhu, Wei-Pu; Shen, Zhi-Quan

2010-04-12

Novel drug-conjugated amphiphilic A(14)B(7) miktoarm star copolymers composed of 14 poly(epsilon-caprolactone) (PCL) arms and 7 poly(ethylene glycol) (PEG) arms with beta-cyclodextrin (beta-CD) as core moiety were synthesized by the combination of controlled ring-opening polymerization (CROP) and "click" chemistry. (1)H NMR, FT-IR, and SEC-MALLS analyses confirmed the well-defined A(14)B(7) miktoarm star architecture. These amphiphilic miktoarm star copolymers could self-assemble into multimorphological aggregates in aqueous solution, which were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, the drug-loading efficiency and drug-encapsulation efficiency of the drug-conjugated miktoarm star copolymers were higher than those of the corresponding non-drug-conjugated miktoarm star copolymers.

Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia

PubMed Central

Briot, Thomas; Roger, Emilie; Lautram, Nolwenn; Verger, Alexis; Clavreul, Anne; Lagarce, Frederic

2017-01-01

Decitabine is a hydrophilic drug that acts by hypomethylating DNA. Decitabine is used in Europe for the treatment of acute myeloid leukemia (AML) in patients aged ≥65 years. However, it can only be administered intravenously due to very low oral bioavailability and a large distribution volume. Oral administration would allow outpatient treatment, improving quality of life and reducing treatment costs. The present study proposes to develop lipid nanocapsules (LNCs), originally designed for lipophilic drugs, to encapsulate decitabine. Two different formulations of LNCs were designed: LNCs based on a high proportion of Transcutol® HP (THP-LNCs) and LNCs associated with a mixture of Transcutol® HP and Tween® 80 (THP-T80-LNCs). The second formulation had a diameter of 26.5±0.5 nm, high encapsulation efficiency (>85%), and a drug payload of 472±64 µg/mL. Decitabine-loaded THP-T80-LNC cytotoxicity was evaluated on two AML cell lines depending on their decitabine resistance: HEL (not resistant) and HL-60 (resistant). The permeability of decitabine-loaded THP-T80-LNCs was also evaluated on Caco-2 cell monolayers. Decitabine cytotoxicity against HEL and HL-60 was higher when decitabine was loaded in THP-T80-LNCs than when free. Apparent permeability on Caco-2 cell monolayers was also increased, suggesting a potentially useful formulation to increase the oral bioavailability of decitabine. PMID:29200853

Nebulization performance of biodegradable sildenafil-loaded nanoparticles using the Aeroneb Pro: formulation aspects and nanoparticle stability to nebulization.

PubMed

Beck-Broichsitter, Moritz; Kleimann, Pia; Gessler, Tobias; Seeger, Werner; Kissel, Thomas; Schmehl, Thomas

2012-01-17

Polymeric nanoparticles meet the increasing interest for drug delivery applications and hold great promise to improve controlled drug delivery to the lung. Here, we present a series of investigations that were carried out to understand the impact of formulation variables on the nebulization performance of novel biodegradable sildenafil-loaded nanoparticles designed for targeted aerosol therapy of life-threatening pulmonary arterial hypertension. Narrowly distributed poly(D,L-lactide-co-glycolide) nanoparticles (size: ∼200 nm) were prepared by a solvent evaporation technique using poly(vinyl alcohol) (PVA) as stabilizer. The aerodynamic and output characteristics using the Aeroneb Pro nebulizer correlated well with the dynamic viscosity of the employed fluids for nebulization. The nebulization performance was mainly affected by the amount of employed stabilizer, rather than by the applied nanoparticle concentration. Nanoparticles revealed physical stability against forces generated during aerosolization, what is attributed to the adsorbed PVA layer around the nanoparticles. Sildenafil was successfully encapsulated into nanoparticles (encapsulation efficiency: ∼80%). Size, size distribution and sildenafil content of nanoparticles were not affected by nebulization and the in vitro drug release profile demonstrated a sustained sildenafil release over ∼120 min. The current study suggests that the prepared sildenafil-loaded nanoparticles are a promising pharmaceutical for the therapy of pulmonary arterial hypertension. Copyright © 2011 Elsevier B.V. All rights reserved.

Development and evaluation of nanoparticles based on mPEG-PLA for controlled delivery of vinpocetine: in vitro and in vivo studies.

PubMed

Wang, Run; Xu, Yong

2017-02-01

The aim of present study was to develop VIN-loaded mPEG-PLA nanoparticle systems. The VIN mPEG-PLA nanoparticles were prepared using an emulsion solvent evaporation method, and studied their particle size, morphology, encapsulation efficiency and drug-loading coefficient. Moreover, the nanoparticles were evaluated on the drug release behaviors in vitro and bioavailability in vivo. The results show that the spherical nanoparticles obtained were negatively charged with a zeta potential of about -23.4 mV and characterized ∼110 nm with a narrow size distribution. The encapsulation efficiency and drug loading of prepared NPs were 76.4 ± 6.3 and 9.2 ± 2.2% (n=5), respectively. The in vitro release showed that the percent of accumulated dissolution of VIN NPs in phosphate-buffered saline 6.8 over 24 h was <80%, which was almost 100% of VIN in commercial injections. The in vivo study indicated that systemic absorption of VIN was significantly enhanced by incorporating into mPEG-PLA NPs compared with VIN injection (2.87-fold in AUC 0- t ). The results suggested that the form of VIN in mPEG-PLA NPs could enter the body circulation to perform sustained release in vitro and in vivo.

Multifunctional SPIO/DOX-loaded A54 Homing Peptide Functionalized Dextran-g-PLGA Micelles for Tumor Therapy and MR Imaging

NASA Astrophysics Data System (ADS)

Situ, Jun-Qing; Wang, Xiao-Juan; Zhu, Xiu-Liang; Xu, Xiao-Ling; Kang, Xu-Qi; Hu, Jing-Bo; Lu, Chen-Ying; Ying, Xiao-Ying; Yu, Ri-Sheng; You, Jian; Du, Yong-Zhong

2016-10-01

Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 μg. mL-1 and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI. The drug-encapsulation efficiency was about 80% and the in vitro DOX release was prolonged to 72 hours. The DOX/SPIO-loaded micelles could specifically target BEL-7402 cell line. In vitro MRI results also proved the specific binding ability of A54-Dex-PLGA/DOX/SPIO micelles to hepatoma cell BEL-7402. The in vivo MR imaging experiments using a BEL-7402 orthotopic implantation model further validated the targeting effect of DOX/SPIO-loaded micelles. In vitro and in vivo anti-tumor activities results showed that A54-Dex-PLGA/DOX/SPIO micelles revealed better therapeutic effects compared with Dex-PLGA/DOX/SPIO micelles and reduced toxicity compared with commercial adriamycin injection.

Effect of polymer architecture on curcumin encapsulation and release from PEGylated polymer nanoparticles: Toward a drug delivery nano-platform to the CNS.

PubMed

Rabanel, Jean-Michel; Faivre, Jimmy; Paka, Ghislain Djiokeng; Ramassamy, Charles; Hildgen, Patrice; Banquy, Xavier

2015-10-01

We developed a nanoparticles (NPs) library from poly(ethylene glycol)-poly lactic acid comb-like polymers with variable amount of PEG. Curcumin was encapsulated in the NPs with a view to develop a delivery platform to treat diseases involving oxidative stress affecting the CNS. We observed a sharp decrease in size between 15 and 20% w/w of PEG which corresponds to a transition from a large solid particle structure to a "micelle-like" or "polymer nano-aggregate" structure. Drug loading, loading efficacy and release kinetics were determined. The diffusion coefficients of curcumin in NPs were determined using a mathematical modeling. The higher diffusion was observed for solid particles compared to "polymer nano-aggregate" particles. NPs did not present any significant toxicity when tested in vitro on a neuronal cell line. Moreover, the ability of NPs carrying curcumin to prevent oxidative stress was evidenced and linked to polymer architecture and NPs organization. Our study showed the intimate relationship between the polymer architecture and the biophysical properties of the resulting NPs and sheds light on new approaches to design efficient NP-based drug carriers. Copyright © 2015 Elsevier B.V. All rights reserved.

β-casein nanovehicles for oral delivery of chemotherapeutic Drug combinations overcoming P-glycoprotein-mediated multidrug resistance in human gastric cancer cells.

PubMed

Bar-Zeev, Maya; Assaraf, Yehuda G; Livney, Yoav D

2016-04-26

Multidrug resistance (MDR) is a primary obstacle to curative cancer therapy. We have previously demonstrated that β-casein (β-CN) micelles (β-CM) can serve as nanovehicles for oral delivery and target-activated release of hydrophobic drugs in the stomach. Herein we introduce a novel nanosystem based on β-CM, to orally deliver a synergistic combination of a chemotherapeutic drug (Paclitaxel) and a P-glycoprotein-specific transport inhibitor (Tariquidar) individually encapsulated within β-CM, for overcoming MDR in gastric cancer. Light microscopy, dynamic light scattering and zeta potential analyses revealed solubilization of these drugs by β-CN, suppressing drug crystallization. Spectrophotometry demonstrated high loading capacity and good encapsulation efficiency, whereas spectrofluorometry revealed high affinity of these drugs to β-CN. In vitro cytotoxicity assays exhibited remarkable synergistic efficacy against human MDR gastric carcinoma cells with P-glycoprotein overexpression. Oral delivery of β-CN - based nanovehicles carrying synergistic drug combinations to the stomach constitutes a novel efficacious therapeutic system that may overcome MDR in gastric cancer.

Quercetin and doxorubicin co-encapsulated biotin receptor-targeting nanoparticles for minimizing drug resistance in breast cancer.

PubMed

Lv, Li; Liu, Chunxia; Chen, Chuxiong; Yu, Xiaoxia; Chen, Guanghui; Shi, Yonghui; Qin, Fengchao; Ou, Jiebin; Qiu, Kaifeng; Li, Guocheng

2016-05-31

The combination of a chemotherapeutic drug with a chemosensitizer has emerged as a promising strategy for cancers showing multidrug resistance (MDR). Herein we describe the simultaneous targeted delivery of two drugs to tumor cells by using biotin-decorated poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles encapsulating the chemotherapeutic drug doxorubicin and the chemosensitizer quercetin (BNDQ). Next, the potential ability of BNDQ to reverse MDR in vitro and in vivo was investigated. Studies demonstrated that BNDQ was more effectively taken up with less efflux by doxorubicin-resistant MCF-7 breast cancer cells (MCF-7/ADR cells) than by the cells treated with the free drugs, single-drug-loaded nanoparticles, or non-biotin-decorated nanoparticles. BNDQ exhibited clear inhibition of both the activity and expression of P-glycoprotein in MCF-7/ADR cells. More importantly, it caused a significant reduction in doxorubicin resistance in MCF-7/ADR breast cancer cells both in vitro and in vivo, among all the groups. Overall, this study suggests that BNDQ has a potential role in the treatment of drug-resistant breast cancer.

Development and Characterization of Methylene Blue Oleate Salt-Loaded Polymeric Nanoparticles and their Potential Application as a Treatment for Glioblastoma

PubMed Central

Castañeda-Gill, JM; Ranjan, AP; Vishwanatha, JK

2017-01-01

Glioblastoma (GBM) is an aggressive, grade IV brain tumor that develops from astrocytes located within the cerebrum, resulting in poor prognosis and survival rates following an accepted treatment regimen of surgery, radiation, and temozolomide. Thus, development of new therapeutics is necessary. During the last two decades, methylene blue (MB) has received increased attention as a potential neurotherapeutic due to its duality in brain cancers and neurodegenerative diseases. While MB is capable of easily permeating the blood-brain barrier, its therapeutic concentrations in GBM are known to induce off-target cytotoxicity and thus, another mode of drug delivery must be considered. To this end, encapsulation of formerly unusable compounds into nanoparticles (NPs) made from the biodegradable/biocompatible, FDA approved co-polymer poly (lactide-co-glycolide) (PLGA) has been more commonplace when developing novel therapeutics. In this study, we formulated and characterized Pluronic F68-coated PLGA NPs containing a sodium oleate conjugate of MB (MBOS) via solvent displacement. Conjugation of sodium oleate to MB was shown to reduce its release from PLGA NPs compared to unmodified MB, leading to potential improvements in drug accumulation and therapeutic effectiveness. Our drug-loaded NP preparations, which were ~170 nm in size and had drug loading values of ~2%, were shown to reduce cell viability and cell compartment-specific, as well as overall cell, functions equivalenty, if not more so, when compared to free drug in two GBM cell lines. Following bio-distribution analysis of free MBOS compared to its nano-encapsulated counterpart, drug-loaded NPs were shown to more effectively permeate the BBB, which could lead to improvements in therapeutic effectiveness upon further examination in a tumor-bearing mouse model. Based on these results, we believe that the further development and eventual utilization of this nanoformulation could lead to an effective GBM therapy that could extend patient survival rates. PMID:29034126

Conjugation of arginine-glycine-aspartic acid peptides to poly(ethylene oxide)-b-poly(epsilon-caprolactone) micelles for enhanced intracellular drug delivery to metastatic tumor cells.

PubMed

Xiong, Xiao-Bing; Mahmud, Abdullah; Uludağ, Hasan; Lavasanifar, Afsaneh

2007-03-01

An arginine-glycine-aspartic acid (RGD) containing model peptide was conjugated to the surface of poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) micelles as a ligand that can recognize adhesion molecules overexpressed on the surface of metastatic cancer cells, that is, integrins, and that can enhance the micellar delivery of encapsulated hydrophobic drug into a tumor cell. Toward this goal, PEO-b-PCL copolymers bearing acetal groups on the PEO end were synthesized, characterized, and assembled to polymeric micelles. The acetal group on the surface of the PEO-b-PCL micelles was converted to reactive aldehyde under acidic condition at room temperature. An RGD-containing linear peptide, GRGDS, was conjugated on the surface of the aldehyde-decorated PEO-b-PCL micelles by incubation at room temperature. A hydrophobic fluorescent probe, that is, DiI, was physically loaded in prepared polymeric micelles to imitate hydrophobic drugs loaded in micellar carrier. The cellular uptake of DiI loaded GRGDS-modified micelles by melanoma B16-F10 cells was investigated at 4 and 37 degrees C by fluorescent spectroscopy and confocal microscopy techniques and was compared to the uptake of DiI loaded valine-PEO-b-PCL micelles (as the irrelevant ligand decorated micelles) and free DiI. GRGDS conjugation to polymeric micelles significantly facilitated the cellular uptake of encapsulated hydrophobic DiI most probably by intergrin-mediated cell attachment and endocytosis. The results indicate that acetal-terminated PEO-b-PCL micelles are amenable for introducing targeting moieties on the surface of polymeric micelles and that RGD-peptide conjugated PEO-b-PCL micelles are promising ligand-targeted carriers for enhanced drug delivery to metastatic tumor cells.

Transcriptional transactivator peptide modified lidocaine-loaded nanoparticulate drug delivery system for topical anesthetic therapy.

PubMed

Wang, Yan; Wang, Shenhui; Shi, Pengcai

2016-11-01

For the topical anesthetic, transcriptional transactivator peptide (TAT) modified lidocaine (LID) loaded nanostructured lipid carriers (TAT-NLCs-LID) were prepared and then used for improving transdermal delivery of local anesthetic drug. In this study, TAT was conjugated with Distearoyl phosphatidylethanolamine-(polyethylene glycol) 2000 -maleimide (DSPE-PEG 2000 -Mal) to obtain TAT-PEG 2000 -DSPE. TAT-NLCs-LID were successfully prepared and characterized by determination of their particle size, morphology, drug encapsulation efficiency and in vitro drug release behavior. The skin permeation of LID-LNPs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro and in vivo anesthesia effect was evaluated on mice. The results showed that TAT-NLCs-LID have substantially small mean diameter (157.9 nm) and high encapsulation efficiency (81.8%). From the in vitro skin permeation results, transdermal flux of TAT-NLCs-LID was about several times higher than that of LID solution and NLCs-LID. In vivo anesthesia effect evaluation illustrated that TAT-NLCs-LID can enhance the transdermal delivery of LID by reducing the pain threshold in mice. These results indicate that the novel TAT containing drug delivery system is very useful for overcoming the barrier function of the skin and could deliver anesthetic through the skin. TAT-NLCs-LID could function as promising topical anesthetic system.

Enhanced Transdermal Delivery by Combined Application of Dissolving Microneedle Patch on Serum-Treated Skin.

PubMed

Kim, Suyong; Dangol, Manita; Kang, Geonwoo; Lahiji, Shayan F; Yang, Huisuk; Jang, Mingyu; Ma, Yonghao; Li, Chengguo; Lee, Sang Gon; Kim, Chang Hyun; Choi, Young Wook; Kim, So Jeong; Ryu, Ja Hyun; Baek, Ji Hwoon; Koh, Jaesuk; Jung, Hyungil

2017-06-05

Dissolving microneedle (DMN), a transdermal drug delivery system in which drugs are encapsulated in a biodegradable polymeric microstructure, is designed to dissolve after skin penetration and release the encapsulated drugs into the body. However, because of limited loading capacity of drugs within microsized structures, only a small dosage can be delivered, which is often insufficient for patients. We propose a novel DMN application that combines topical and DMN application simultaneously to improve skin permeation efficiency. Drugs in pretreated topical formulation and encapsulated drugs in DMN patch are delivered into the skin through microchannels created by DMN application, thus greatly increasing the delivered dose. We used 4-n-butylresorcinol to treat human hyperpigmentation and found that sequential application of serum formulation and DMNs was successful. In skin distribution experiments using Alexa Fluor 488 and 568 dyes as model drugs, we confirmed that the pretreated serum formulation was delivered into the skin through microchannels created by the DMNs. In vitro skin permeation and retention experiments confirmed that this novel combined application delivered more 4-n-butylresorcinol into the skin than traditional DMN-only and serum-only applications. Moreover, this combined application showed a higher efficacy in reducing patients' melanin index and hyperpigmented regions compared with the serum-only application. As combined application of DMNs on serum-treated skin can overcome both dose limitations and safety concerns, this novel approach can advance developments in transdermal drug delivery.

Microfluidic assembly of monodisperse multistage pH-responsive polymer/porous silicon composites for precisely controlled multi-drug delivery.

PubMed

Liu, Dongfei; Zhang, Hongbo; Herranz-Blanco, Bárbara; Mäkilä, Ermei; Lehto, Vesa-Pekka; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2014-05-28

We report an advanced drug delivery platform for combination chemotherapy by concurrently incorporating two different drugs into microcompoistes with ratiometric control over the loading degree. Atorvastatin and celecoxib were selected as model drugs due to their different physicochemical properties and synergetic effect on colorectal cancer prevention and inhibition. To be effective in colorectal cancer prevention and inhibition, the produced microcomposite contained hypromellose acetate succinate, which is insoluble in acidic conditions but highly dissolving at neutral or alkaline pH conditions. Taking advantage of the large pore volume of porous silicon (PSi), atorvastatin was firstly loaded into the PSi matrix, and then encapsulated into the pH-responsive polymer microparticles containing celecoxib by microfluidics in order to obtain multi-drug loaded polymer/PSi microcomposites. The prepared microcomposites showed monodisperse size distribution, multistage pH-response, precise ratiometric controlled loading degree towards the simultaneously loaded drug molecules, and tailored release kinetics of the loaded cargos. This attractive microcomposite platform protects the payloads from being released at low pH-values, and enhances their release at higher pH-values, which can be further used for colon cancer prevention and treatment. Overall, the pH-responsive polymer/PSi-based microcomposite can be used as a universal platform for the delivery of different drug molecules for combination therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Delivery of drugs bound to erythrocytes: new avenues for an old intravascular carrier

PubMed Central

Villa, Carlos H; Pan, Daniel C; Zaitsev, Sergei; Cines, Douglas B; Siegel, Donald L; Muzykantov, Vladimir R

2015-01-01

For several decades, researchers have used erythrocytes for drug delivery of a wide variety of therapeutics in order to improve their pharmacokinetics, biodistribution, controlled release and pharmacodynamics. Approaches include encapsulation of drugs within erythrocytes, as well as coupling of drugs onto the red cell surface. This review focuses on the latter approach, and examines the delivery of red blood cell (RBC)-surface-bound anti-inflammatory, anti-thrombotic and anti-microbial agents, as well as RBC carriage of nanoparticles. Herein, we discuss the progress that has been made in surface loading approaches, and address in depth the issues relevant to surface loading of RBC, including intrinsic features of erythrocyte membranes, immune considerations, potential surface targets and techniques for the production of affinity ligands. PMID:26228773

Effects of melamine formaldehyde resin and CaCO3 diffuser-loaded encapsulation on correlated color temperature uniformity of phosphor-converted LEDs.

PubMed

Yang, Liang; Lv, Zhicheng; Jiaojiao, Yuan; Liu, Sheng

2013-08-01

Phosphor-free dispensing is the most widely used LED packaging method, but this method results in poor quality in angular CCT uniformity. This study proposes a diffuser-loaded encapsulation to solve the problem; the effects of melamine formaldehyde (MF) resin and CaCO3 loaded encapsulation on correlated color temperature (CCT) uniformity and luminous efficiency reduction of the phosphor-converted LEDs are investigated. Results reveal that MF resin loaded encapsulation has better light diffusion performance compared to MF resin loaded encapsulation at the same diffuser concentration, but CaCO3 loaded encapsulation has better luminous efficiency maintenance. The improvements in angular color uniformity for the LEDs emitting with MF resin and CaCO3 loaded encapsulation can be explained by the increase in photon scattering. The utility of this low cost and controllable mineral diffuser packaging method provides a practical approach for enhancing the angular color uniformity of LEDs. The diffuser mass ratio of 1% MF resin or 10% CaCO3 is the optimum condition to obtain low angular CCT variance and high luminous efficiency.

A combined interfacial and in-situ polymerization strategy to construct well-defined core-shell epoxy-containing SiO2-based microcapsules with high encapsulation loading, super thermal stability and nonpolar solvent tolerance

NASA Astrophysics Data System (ADS)

Jia; Wang; Tian; Li; Xu; Jiao; Cao; Wu

2016-10-01

SiO2-based microcapsules containing hydrophobic molecules exhibited potential applications such as extrinsic self-healing, drug delivery, due to outstanding thermal and chemical stability of SiO2. However, to construct SiO2-based microcapsules with both high encapsulation loading and long-term structural stability is still a troublesome issue, limiting their further utilization. We herein design a single-batch route, a combined interfacial and in-situ polymerization strategy, to fabricate epoxy-containing SiO2-based microcapsules with both high encapsulation loading and long-term structural stability. The final SiO2-based microcapsules preserve high encapsulation loading of 85.7 wt% by controlling exclusively hydrolysis and condensed polymerization at oil/water interface in the initial interfacial polymerization step. In the subsequent in-situ polymerization step, the initial SiO2-based microcapsules as seeds could efficiently harvest SiO2 precursors and primary SiO2 particles to finely tune the SiO2 wall thickness, thereby enhancing long-term structural stability of the final SiO2-based microcapsules including high thermal stability with almost no any weight loss until 250°C, and strong tolerance against nonpolar solvents such as CCl4 with almost unchanged core-shell structure and unchanged core weight after immersing into strong solvents for up to 5 days. These SiO2-based microcapsules are extremely suited for processing them into anticorrosive coating in the presence of nonpolar solvents for self-healing application.

First evaluation of drug-in-cyclodextrin-in-liposomes as an encapsulating system for nerolidol.

PubMed

Azzi, Joyce; Auezova, Lizette; Danjou, Pierre-Edouard; Fourmentin, Sophie; Greige-Gerges, Hélène

2018-07-30

Nerolidol, a naturally occurring sesquiterpene with antimicrobial activities, is a promising candidate as a natural alternative for synthetic preservatives in food. However, its application is limited by low aqueous solubility and stability. In this study, conventional liposomes and drug-in-cyclodextrin-in-liposomes (DCLs) were evaluated for the first time as encapsulating materials for nerolidol. The size, encapsulation efficiency (EE%), loading rate (LR%), photo- and storage stabilities of both systems were characterized. Moreover, the in vitro release of nerolidol from liposomes and DCLs was investigated over time. Nerolidol was efficiently entrapped in both carriers with high EE% and LR% values. In addition, DCLs prolonged the release of nerolidol over one week and enhanced the photostability more effectively than conventional liposomes. Finally, all formulations were stable after 12 months of storage at 4 °C (>60% incorporated nerolidol). Therefore, DCLs are promising carriers for new applications of sesquiterpenes in the pharmaceutical and food industries. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preparation and characterization of polymer nanocomposites coated magnetic nanoparticles for drug delivery applications

NASA Astrophysics Data System (ADS)

Prabha, G.; Raj, V.

2016-06-01

In the present research work, the anticancer drug 'curcumin' is loaded with Chitosan (CS)-polyethylene glycol (PEG)-polyvinylpyrrolidone (PVP) (CS-PEG-PVP) polymer nanocomposites coated with superparamagnetic iron oxide (Fe3O4) nanoparticles. The system can be used for targeted and controlled drug delivery of anticancer drugs with reduced side effects and greater efficiency. The prepared nanoparticles were characterized by Fourier transmission infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Curcumin drug loaded Fe3O4-CS, Fe3O4-CS-PEG and Fe3O4-CS-PEG-PVP nanoparticles exhibited the mean particle size in the range of 183-390 nm with a zeta potential value of 26-41 mV as measured using Malvern Zetasizer. The encapsulation efficiency, loading capacity and in-vitro drug release behavior of curcumin drug loaded Fe3O4-CS, Fe3O4-CS-PEG and Fe3O4-CS-PEG-PVP nanoparticles were studied using UV spectrophotometer. Besides, the cytotoxicity of the prepared nanoparticles using MTT assay was also studied. The curcumin drug release was examined at different pH medium and it was proved that the drug release depends upon the pH medium in addition to the nature of matrix.

The size-reduced Eudragit® RS microparticles prepared by solvent evaporation method - monitoring the effect of selected variables on tested parameters.

PubMed

Vasileiou, Kalliopi; Vysloužil, Jakub; Pavelková, Miroslava; Vysloužil, Jan; Kubová, Kateřina

2018-01-01

Size-reduced microparticles were successfully obtained by solvent evaporation method. Different parameters were applied in each sample and their influence on microparticles was evaluated. As a model drug the insoluble ibuprofen was selected for the encapsulation process with Eudragit® RS. The obtained microparticles were inspected by optical microscopy and scanning electron microscopy. The effect of aqueous phase volume (600, 400, 200 ml) and the concentration of polyvinyl alcohol (PVA; 1.0% and 0.1%) were studied. It was evaluated how those variations and also size can affect microparticle characteristics such as encapsulation efficiency, drug loading, burst effect and microparticle morphology. It was observed that the sample prepared with 600 ml aqueous phase and 1% concentration of polyvinyl alcohol gave the most favorable results.Key words: microparticles solvent evaporation sustained drug release Eudragit RS®.

Controlled Release of Nor-β-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells.

PubMed

Costa, Marcilia P; Feitosa, Anderson C S; Oliveira, Fátima C E; Cavalcanti, Bruno C; da Silva, Eufrânio N; Dias, Gleiston G; Sales, Francisco A M; Sousa, Bruno L; Barroso-Neto, Ito L; Pessoa, Cláudia; Caetano, Ewerton W S; Di Fiore, Stefano; Fischer, Rainer; Ladeira, Luiz O; Freire, Valder N

2016-07-02

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-β-lapachone (NβL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 μm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NβL on PLGA. Finally, the cytotoxic activity of NβL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.

Development and evaluation of a novel topical treatment for acne with azelaic acid-loaded nanoparticles.

PubMed

Reis, Catarina Pinto; Gomes, Ana; Rijo, Patrícia; Candeias, Sara; Pinto, Pedro; Baptista, Marina; Martinho, Nuno; Ascensão, Lia

2013-10-01

Azelaic acid (AzA) is used in the treatment of acne. However, side effects and low compliance have been associated with several topical treatments with AzA. Nanotechnology presents a strategy that can overcome these problems. Polymeric nanoparticles can control drug release and targeting and reduce local drug toxicity. The aim of this study was to produce and evaluate an innovative topical treatment for acne with AzA-loaded poly-DL-lactide/glycolide copolymer nanoparticles. A soft white powder of nanoparticles was prepared. The mean size of loaded nanoparticles was < 400 nm and zeta potential was negative. Spherical nanoparticles were observed by scanning electron microscopy. Encapsulation efficiency was around 80% and a strong interaction between the polymer and the drug was confirmed by differential scanning calorimetric analysis. In vitro drug release studies suggested a controlled and pulsatile release profile. System efficacy tests suggested similar results between the loaded nanoparticles and the nonencapsulated drug against the most common bacteria associated with acne. Cytotoxicity of AzA-loaded nanoparticles was concentration dependent, although not pronounced. The occluded patch test seemed to indicate that the formulation excipients were safe and thus AzA-loaded nanoparticles appear to be an efficient and safe treatment for acne.

Formulation and evaluation of lidocaine base ethosomes for transdermal delivery.

PubMed

Zhu, Xiaoliang; Li, Fuli; Peng, Xuebiao; Zeng, Kang

2013-08-01

Although transdermal preparations of local anesthetics have been used to reduce pain caused by skin surgery, these preparations cannot effectively penetrate through the epidermis because of the barrier formed by the stratum corneum and the thick epidermis. Ethosomes can effectively transport drugs across the skin because of their thermodynamic stability, small size, high encapsulation efficiency, and percutaneous penetration. We evaluated lidocaine base ethosomes by measuring their loading efficiency, encapsulation efficiency, thermodynamic stability, and percutaneous penetration capability in vitro, and their effectiveness and cutaneous irritation in vivo. Lidocaine base ethosomes were prepared using the injection-sonication-filter method. Size, loading efficiency, encapsulation efficiency, and stability were evaluated using a Zetasizer and high performance liquid chromatography. Formulation was determined by measuring the maximum encapsulation efficiency in the orthogonal test. Percutaneous penetration efficiency in vitro was analyzed using a Franz-type diffusion cell experiment. In vivo effectiveness was analyzed using the pinprick test. Cutaneous irritancy tests were performed on white guinea pigs, followed by histopathologic analysis. The results were compared with lidocaine liposomes as well as lidocaine delivered in a hydroethanolic solution. Lidocaine base ethosomes composed of 5% (w/w) egg phosphatidyl choline, 35% (w/w) ethanol, 0.2% (w/w) cholesterol, 5% (w/w) lidocaine base, and ultrapure water had a mean maximum encapsulation of 51% ± 4%, a mean particle size of 31 ± 3 nm, and a mean loading efficiency of 95.0% ± 0.1%. The encapsulation efficiency of lidocaine base ethosomes remained stable for 60 days at 25°C ± 1°C (95% confidence interval [CI], -1.12% to 1.34%; P = 0.833). The transdermal flux of lidocaine base differed significantly for the 3 preparations (F = 120, P < 0.001), being significantly greater from ethosomes than from liposomes (95% corrected CI, 1129-1818 µg/(cm(2)·h); P < 0.001), and from hydroethanolic solution (95% corrected CI, 1468-2157 µg/(cm(2)·h); P < 0.001). Lidocaine base ethosomes had a shorter onset time and longer duration in vivo than did lidocaine base liposomes or lidocaine delivered in a hydroethanolic solution. Lidocaine base ethosomes showed no evidence of dermal irritation in guinea pigs. Ethosomes are potential carriers of local anesthetics across the skin and may have applicability for other percutaneous drugs that require rapid onset.

Preparation of solid lipid nanoparticles from W/O/W emulsions: preliminary studies on insulin encapsulation.

PubMed

Gallarate, Marina; Trotta, Michele; Battaglia, Luigi; Chirio, Daniela

2009-08-01

A method to produce solid lipid nanoparticles (SLN) from W/O/W multiple emulsions was developed applying the solvent-in-water emulsion-diffusion technique. Insulin was chosen as hydrophilic peptide drug to be dissolved in the acidic inner aqueous phase of multiple emulsions and to be consequently carried in SLN. Several partially water-miscible solvents with low toxicity were screened in order to optimize emulsions and SLN composition, after assessing that insulin did not undergo any chemical modification in the presence of the different solvents and under the production process conditions. SLN of spherical shape and with mean diameters in the 600-1200 nm range were obtained by simple water dilution of the W/O/W emulsion. Best results, in terms of SLN mean diameter and encapsulation efficiencies, were obtained using glyceryl monostearate as lipid matrix, butyl lactate as a solvent, and soy lecithin and Pluronic F68 as surfactants. Encapsulation efficiencies up to 40% of the loaded amount were obtained, owing to the actual multiplicity of the system; the use of multiple emulsion-derived SLN can be considered a useful strategy to encapsulate a hydrophilic drug in a lipid matrix.

Encapsulation of a proteasome inhibitor with gold-polysaccharide nanocarriers

NASA Astrophysics Data System (ADS)

Coelho, Sílvia Castro; Rocha, Sandra; Sampaio, Paula; Pereira, Maria Carmo; Coelho, Manuel A. N.

2014-04-01

Organic-inorganic hybrid nanoparticles are potential effective systems for drug delivery in cancer therapy and diagnosis. Chitosan-gum arabic with entrapped gold nanoparticles were developed as a carrier for an anticancer drug bortezomib. The nanosystem was designed to enhance the proteasome inhibitor activity in pancreatic cell lines, S2-013 and hTERT-HPNE. The hydrodynamic diameter of chitosan-gum arabic-gold nanoparticles loaded with bortezomib is around 330 nm. Laser scanning confocal microscopy images show the uptake of the gold nanoparticle/bortezomib encapsulated in chitosan-gum arabic matrix and the fast internalization of these nano combinations into pancreatic cells. Cytotoxic assays assessed that positively charged nanosystems reduce the cell growth and cell proliferation of S2-013s, but the same effect was not observed in cytotoxic response in hTERT-HPNE cells. The outcomes of this study demonstrate the capacity of chitosan-gum arabic nanocarriers to deliver gold nanoparticles/anticancer drug and to increase the permeation and retention effect in S2-013 cells and minimize drug side effects in HPNE cells.

Preparation and characterization of bee venom-loaded PLGA particles for sustained release.

PubMed

Park, Min-Ho; Jun, Hye-Suk; Jeon, Jong-Woon; Park, Jin-Kyu; Lee, Bong-Joo; Suh, Guk-Hyun; Park, Jeong-Sook; Cho, Cheong-Weon

2016-12-14

Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients' quality of life by reducing the number of injections required.

Development of native and modified banana starch nanoparticles as vehicles for curcumin.

PubMed

Acevedo-Guevara, Leonardo; Nieto-Suaza, Leonardo; Sanchez, Leidy T; Pinzon, Magda I; Villa, Cristian C

2018-05-01

In recent years, starch nanoparticles have been of great interest for drug delivery due to their relatively easy synthesis, biocompatibility, and vast amount of botanical sources. Native and acetylated starch obtained from green bananas were used for synthesis of curcumin-loaded starch nanoparticles. Mean particle size, encapsulation efficiency, and curcumin release in simulated gastric and intestinal fluids were studied. Both nanosystems showed sizes lower than 250 nm and encapsulation efficiency above 80%, with acetylated banana starch nanoparticles having the capacity to encapsulate more curcumin molecules. Both FTIR and XRD analyses showed that starch acetylation allows stronger hydrogen bond interaction between curcumin and the starch matrix, thus, higher encapsulation efficiency. Finally, curcumin release studies showed that acetylated banana starch nanoparticles allowed more controlled release, probably due to their stronger hydrogen bond interaction with curcumin. Copyright © 2018. Published by Elsevier B.V.

Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.

PubMed

Alibolandi, Mona; Taghdisi, Seyed Mohammad; Ramezani, Pouria; Hosseini Shamili, Fazileh; Farzad, Sara Amel; Abnous, Khalil; Ramezani, Mohammad

2017-03-15

In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.1% and 93.67% respectively. The in vitro release of camptothecin from the formulation was provided the sustained release of encapsulated camptothecin during 4days. Comparative in vitro cytotoxicity experiments demonstrated that the targeted camptothecin loaded-pegylated dendrimers had higher antiproliferation activity, towards nucleolin-positive HT29 and C26 colorectal cancer cells than nucleolin-negative CHO cell line. Fluorscence microscopy and flow cytometry also confirmed the enhanced cellular uptake of AS1411 targeted pegylated-dendrimer. In vivo study in C26 tumor-bearing BALB/C mice revealed that the AS1411-functionalized camptothecin loaded pegylated dendrimers improved antitumor activity and survival rate of the encapsulated camptothecin. Conjugation of AS1411 aptamer to the camptothecin loaded-pegylated dendrimer surface provides site-specific delivery of camptothecin, inhibit C26 tumor growth in vivo and significantly decrease systemic toxicity. These results suggested that the new nucleolin-targeted pegylated PAMAM dendrimer as a delivery system for camptothecin have the potential for the treatment of nucleolin-overexpressed colorectal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

The impact of calcium carbonate as pore forming agent and drug entrapment method towards drug dissolution mechanism of amoxicillin trihydrate encapsulated by chitosan-methyl cellulose semi-IPN hydrogel for floating drug delivery system

NASA Astrophysics Data System (ADS)

Dewantara, Fauzi; Budianto, Emil

2018-04-01

Chitosan-methyl cellulose semi-IPN hydrogel is used as floating drug delivery system, and calcium carbonate also added as pore forming agent. The hydrogel network arranged by not only using biopolymer chitosan and methyl cellulose, but also the crosslink agent that is glutaraldehyde. Amoxicillin trihydrate entrapped into the polymer network with two different method, in situ loading and post loading. Furthermore both method has been tested for drug entrapment efficiency along with drug dissolution test, and the result for drug entrapment efficiency is in situ loading method has highest value of 100%, compared to post loading method which has value only 71%. Moreover, at the final time of drug dissolution test shows in situ loading method has value of 96% for total accumulative of drug dissolution, meanwhile post loading method has 72%. The value of drug dissolution test from both method is used for analyzing drug dissolution mechanism of amoxicillin trihydrate from hydrogel network with four mathematical drug mechanism models as parameter. The polymer network encounter destructive degradation causes by acid solution which used as dissolution medium, and the level of degradation is observed with optical microscope. However the result shows that degradation of the polymer network doesn't affect drug dissolution mechanism directly. Although the pore forming agent causes the pore inside the hydrogel network create interconnection and it was quite influential to drug dissolution mechanism. Interconnected pore is observed with Scanning Electron Microscope (SEM) and shows that the amount and area of interconnected pore inside the hydrogel network is increasing as drug dissolution goes on.

Dual responsive PNIPAM-chitosan targeted magnetic nanopolymers for targeted drug delivery

NASA Astrophysics Data System (ADS)

Yadavalli, Tejabhiram; Ramasamy, Shivaraman; Chandrasekaran, Gopalakrishnan; Michael, Isaac; Therese, Helen Annal; Chennakesavulu, Ramasamy

2015-04-01

A dual stimuli sensitive magnetic hyperthermia based drug delivery system has been developed for targeted cancer treatment. Thermosensitive amine terminated poly-N-isopropylacrylamide complexed with pH sensitive chitosan nanoparticles was prepared as the drug carrier. Folic acid and fluorescein were tagged to the nanopolymer complex via N-hydroxysuccinimide and ethyl-3-(3-dimethylaminopropyl)carbodiimide reaction to form a fluorescent and cancer targeting magnetic carrier system. The formation of the polymer complex was confirmed using infrared spectroscopy. Gadolinium doped nickel ferrite nanoparticles prepared by a hydrothermal method were encapsulated in the polymer complex to form a magnetic drug carrier system. The proton relaxation studies on the magnetic carrier system revealed a 200% increase in the T1 proton relaxation rate. These magnetic carriers were loaded with curcumin using solvent evaporation method with a drug loading efficiency of 86%. Drug loaded nanoparticles were tested for their targeting and anticancer properties on four cancer cell lines with the help of MTT assay. The results indicated apoptosis of cancer cell lines within 3 h of incubation.

Ultrasound-mediated drug delivery using liposomes modified with a thermosensitive polymer.

PubMed

Ninomiya, Kazuaki; Kawabata, Shinya; Tashita, Hiroyuki; Shimizu, Nobuaki

2014-01-01

Ultrasound-mediated drug delivery was established using liposomes that were modified with the thermosensitive polymer (TSP) poly(NIPMAM-co-NIPAM), which sensitized the liposomes to high temperatures. TSP-modified liposomes (TSP liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation at 0.5 W/cm(2) for 120 s as well as the case under incubation at 42 °C for 15 min. In addition, uptake of the drug released from TSP liposomes by cancer cells was enhanced by ultrasound irradiation. In a cell injury assay using doxorubicin (DOX)-loaded TSP liposomes and ultrasound irradiation, cell viability of HepG2 cells at 6 h after ultrasound irradiation (1 MHz, 0.5 W/cm(2) for 30 s) with DOX-loaded TSP liposomes (TSP/lipid ratio=1) was 60%, which was significantly lower than that of the control conditions such as DOX-loaded TSP liposomes alone and DOX-loaded intact liposomes under ultrasound irradiation. Copyright © 2013 Elsevier B.V. All rights reserved.

Ion-Pairing Contribution to the Liposomal Transport of Topotecan as Revealed by Mechanistic Modeling.

PubMed

Fugit, Kyle D; Anderson, Bradley D

2017-04-01

Actively loaded liposomal formulations of anticancer agents have been widely explored due to their high drug encapsulation efficiencies and prolonged drug retention. Mathematical models to predict and optimize drug loading and release kinetics from these nanoparticle formulations would be useful in their development and may allow researchers to tune release profiles. Such models must account for the driving forces as influenced by the physicochemical properties of the drug and the microenvironment, and the liposomal barrier properties. This study employed mechanistic modeling to describe the active liposomal loading and release kinetics of the anticancer agent topotecan (TPT). The model incorporates ammonia transport resulting in generation of a pH gradient, TPT dimerization, TPT lactone ring-opening and -closing interconversion kinetics, chloride transport, and transport of TPT-chloride ion-pairs to describe the active loading and release kinetics of TPT in the presence of varying chloride concentrations. Model-based predictions of the kinetics of active loading at varying loading concentrations of TPT and release under dynamic dialysis conditions were in reasonable agreement with experiments. These findings identify key attributes to consider in optimizing and predicting loading and release of liposomal TPT that may also be applicable to liposomal formulations of other weakly basic pharmaceuticals. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Polyelectrolyte Multilayer Film Coated Silver Nanorods: An Effective Carrier System for Externally Activated Drug Delivery

NASA Astrophysics Data System (ADS)

Paramasivam, Gokul; Sharma, Varsha; Sundaramurthy, Anandhakumar

2017-08-01

Nanoparticle anisotropy offers unique functions and features in comparison with spherical nanoparticles (NPs) and makes anisotropic nanoparticles (ANPs) promising candidates in applications like drug delivery, imaging, biosensing and theranostics. Presence of surface active groups (e.g. amine, and carboxylate groups) on their surface provides binding sites for ligands or other biomolecules, and hence, this could be targeted for specific part or cells in our body. In the quest of such surface modification, functionalization of ANPs along Layer-by-Layer (LbL) coating of oppositely charged polyelectrolytes (PE) reduces cellular toxicity and promotes easy encapsulation of drugs. In this work, we report the silver nanorods (AgNRs) synthesis by adsorbate directed synthetic approach using cetyltrimethyl ammonium bromide (CTAB). The formed ANPs is investigated by scanning electron microscopy (SEM) and UV-Visible (UV-Vis) spectroscopy revealing the shaping of AgNRs of 3-16 nm aspect ratio with some presence of triangles. These NRs were further coated with bio polymers of chitosan (CH) and dextran sulphate (DS) through LbL approach and used for encapsulation of water soluble anti-bacterial drugs like ciprofloxacin hydrochloride (CFH). The encapsulation of drugs and profiles of drug release were investigated and compared to that of spherical silver nanoparticles (AgNPs). The added advantages of the proposed drug delivery system (DDS) can be externally activated to release the loaded drug and used as contrast agents for biological imaging under exposure to NIR light. Such system shows unique and attractive characteristics required for drug delivery and bioimaging thus offering the scope for further development as theranostic material.

Evaluation of hypericin-loaded solid lipid nanoparticles: physicochemical properties, photostability and phototoxicity.

PubMed

Youssef, Tareq; Fadel, Maha; Fahmy, Rania; Kassab, Kawser

2012-01-01

Hypericin (HYP), a natural photosensitizer, has powerful photo-oxidizing ability, tumor-seeking characteristics, and minimal dark toxicity; nevertheless, it has proven high lipid solubility compared to its sparingly water soluble nature. Therefore, its formulation into solid lipid nanoparticles (SLNs) has attracted increasing attention as a potential drug-delivery carrier. Two HYP-loaded SLNs formulations were prepared utilizing microemulsion-based technique. Thereafter, the physicochemical properties of the formulations were investigated and evaluated. HYP-loaded SLNs showed spherical shape with mean particle size ranging from 200-300 nm for both formulations (FA and FB). The encapsulation efficiencies reached above 80% and FA showed significant higher encapsulation than FB (P<0.05), also, the thermal analysis using differential scanning calorimetry (DSC) indicated good compatibility between hypericin and lipids forming the cores in both formulations. Spectroscopic measurements of the photostability study showed that hypericin encapsulation into SLNs improved its photostability, compared to free HYP in 0.1% ethanolic solution. However, photocytotoxicity studies on HepG2 cells revealed an evident inhibition of the photodynamic efficacy of HYP-loaded SLNs, compared to free HYP. In conclusion, although the elevated entrapment efficiency of HYP into SLNs increased its photostability, it decreased its phototoxicity which might be due to the quenching deactivation of HYP molecules resulting from SLN compactness and thickness structure. © 2012 Informa Healthcare USA, Inc.

Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation, characterization, plasma, and kidney pharmacokinetics.

PubMed

Wei, Yinghui; Luo, Xiaoting; Guan, Jiani; Ma, Jianping; Zhong, Yicong; Luo, Jingwen; Li, Fanzhu

2017-11-01

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6 ± 5.95 nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71 ± 3.02%, and the drug loading was 1.56 ± 0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC kidney /AUC plasma  = 0.586 ± 0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.

Microfluidic assisted one-step fabrication of porous silicon@acetalated dextran nanocomposites for precisely controlled combination chemotherapy.

PubMed

Liu, Dongfei; Zhang, Hongbo; Mäkilä, Ermei; Fan, Jin; Herranz-Blanco, Bárbara; Wang, Chang-Fang; Rosa, Ricardo; Ribeiro, António J; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2015-01-01

An advanced nanocomposite consisting of an encapsulated porous silicon (PSi) nanoparticle and an acid-degradable acetalated dextran (AcDX) matrix (nano-in-nano), was efficiently fabricated by a one-step microfluidic self-assembly approach. The obtained nano-in-nano PSi@AcDX composites showed improved surface smoothness, homogeneous size distribution, and considerably enhanced cytocompatibility. Furthermore, multiple drugs with different physicochemical properties have been simultaneously loaded into the nanocomposites with a ratiometric control. The release kinetics of all the payloads was predominantly controlled by the decomposition rate of the outer AcDX matrix. To facilitate the intracellular drug delivery, a nona-arginine cell-penetrating peptide (CPP) was chemically conjugated onto the surface of the nanocomposites by oxime click chemistry. Taking advantage of the significantly improved cell uptake, the proliferation of two breast cancer cell lines was markedly inhibited by the CPP-functionalized multidrug-loaded nanocomposites. Overall, this nano-in-nano PSi@polymer composite prepared by the microfluidic self-assembly approach is a universal platform for nanoparticles encapsulation and precisely controlled combination chemotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Self-folding polymeric containers for encapsulation and delivery of drugs

PubMed Central

Fernandes, Rohan; Gracias, David H.

2012-01-01

Self-folding broadly refers to self-assembly processes wherein thin films or interconnected planar templates curve, roll-up or fold into three dimensional (3D) structures such as cylindrical tubes, spirals, corrugated sheets or polyhedra. The process has been demonstrated with metallic, semiconducting and polymeric films and has been used to curve tubes with diameters as small as 2 nm and fold polyhedra as small as 100 nm, with a surface patterning resolution of 15 nm. Self-folding methods are important for drug delivery applications since they provide a means to realize 3D, biocompatible, all-polymeric containers with well-tailored composition, size, shape, wall thickness, porosity, surface patterns and chemistry. Self-folding is also a highly parallel process, and it is possible to encapsulate or self-load therapeutic cargo during assembly. A variety of therapeutic cargos such as small molecules, peptides, proteins, bacteria, fungi and mammalian cells have been encapsulated in self-folded polymeric containers. In this review, we focus on self-folding of all-polymeric containers. We discuss the mechanistic aspects of self-folding of polymeric containers driven by differential stresses or surface tension forces, the applications of self-folding polymers in drug delivery and we outline future challenges. PMID:22425612

High drug load, stable, manufacturable and bioavailable fenofibrate formulations in mesoporous silica: a comparison of spray drying versus solvent impregnation methods.

PubMed

Hong, Shiqi; Shen, Shoucang; Tan, David Cheng Thiam; Ng, Wai Kiong; Liu, Xueming; Chia, Leonard S O; Irwan, Anastasia W; Tan, Reginald; Nowak, Steven A; Marsh, Kennan; Gokhale, Rajeev

2016-01-01

Encapsulation of drugs in mesoporous silica using co-spray drying process has been recently explored as potential industrial method. However, the impact of spray drying on manufacturability, physiochemical stability and bioavailability in relation to conventional drug load processes are yet to be fully investigated. Using a 2(3) factorial design, this study aims to investigate the effect of drug-loading process (co-spray drying and solvent impregnation), mesoporous silica pore size (SBA-15, 6.5 nm and MCM-41, 2.5 nm) and percentage drug load (30% w/w and 50% w/w) on material properties, crystallinity, physicochemical stability, release profiles and bioavailability of fenofibrate (FEN) loaded into mesoporous silica. From the scanning electronic microscopy (SEM) images, powder X-ray diffraction and Differential scanning calorimetry measurements, it is indicated that the co-spray drying process was able to load up to 50% (w/w) FEN in amorphous form onto the mesoporous silica as compared to the 30% (w/w) for solvent impregnation. The in vitro dissolution rate of the co-spray dried formulations was also significantly (p = 0.044) better than solvent impregnated formulations at the same drug loading. Six-month accelerated stability test at 40 °C/75 RH in open dish indicated excellent physical and chemical stability of formulations prepared by both methods. The amorphous state of FEN and the enhanced dissolution profiles were well preserved, and very low levels of degradation were detected after storage. The dog data for the three selected co-spray-dried formulations revealed multiple fold increment in FEN bioavailability compared to the reference crystalline FEN. These results validate the viability of co-spray-dried mesoporous silica formulations with high amorphous drug load as potential drug delivery systems for poorly water soluble drugs.

Indocyanine Green-Encapsulated Hybrid Polymeric Nanomicelles for Photothermal Cancer Therapy.

PubMed

Jian, Wei-Hong; Yu, Ting-Wei; Chen, Chien-Ju; Huang, Wen-Chia; Chiu, Hsin-Cheng; Chiang, Wen-Hsuan

2015-06-09

Indocyanine green (ICG), an FDA approved medical near-infrared (NIR) imaging agent, has been extensively used in cancer theranosis. However, the limited aqueous photostability, rapid body clearance, and poor cellular uptake severely restrict its practical applications. For these problems to be overcome, ICG-encapsulated hybrid polymeric nanomicelles (PNMs) were developed in this work through coassociation of the amphiphilic diblock copolymer poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and hydrophobic electrostatic complexes composed of ICG molecules and branched poly(ethylenimine) (PEI). The ICG-encapsulated hybrid PNMs featured a hydrophobic PLGA/ICG/PEI core stabilized by hydrophilic PEG shells. The encapsulation of electrostatic ICG/PEI complexes into the compact PLGA-rich core not only facilitated the ICG loading but also promoted its aqueous optical stability. The effects of the chain length of PEI in combination with ICG on the physiochemical properties of PNMs and their drug leakage were also investigated. PEI(10k) (10 kDa) could form highly robust and dense complexes with ICG, and thus prominently reduced ICG outflow from the PNMs. The results of in vitro cellular uptake and cytotoxicity studies revealed that the ICG/PEI(10k)-loaded PNMs significantly promoted cellular uptake of ICG by HeLa cells due to their near-neutral surface, and thereby augmented the NIR-triggered hyperthermia effect in destroying cancer cells. These findings strongly indicate that the ICG/PEI10k-loaded PNMs have significant potential for attaining effective cancer imaging and photothermal therapy.

Bile Acid-Based Drug Delivery Systems for Enhanced Doxorubicin Encapsulation: Comparing Hydrophobic and Ionic Interactions in Drug Loading and Release.

PubMed

Cunningham, Alexander J; Robinson, Mattieu; Banquy, Xavier; Leblond, Jeanne; Zhu, X X

2018-03-05

Doxorubicin (Dox) is a drug of choice in the design of drug delivery systems directed toward breast cancers, but is often limited by loading and control over its release from polymer micelles. Bile acid-based block copolymers present certain advantages over traditional polymer-based systems for drug delivery purposes, since they can enable a higher drug loading via the formation of a reservoir through their aggregation process. In this study, hydrophobic and electrostatic interactions are compared for their influence on Dox loading inside cholic acid based block copolymers. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) were grafted from the cholic acid (CA) core yielding a star-shaped block copolymer with 4 arms (CA-(PAGE- b-PEG) 4 ) and then loaded with Dox via a nanoprecipitation technique. A high Dox loading of 14 wt % was achieved via electrostatic as opposed to hydrophobic interactions with or without oleic acid as a cosurfactant. The electrostatic interactions confer a pH responsiveness to the system. 50% of the loaded Dox was released at pH 5 in comparison to 12% at pH 7.4. The nanoparticles with Dox loaded via hydrophobic interactions did not show such a pH responsiveness. The systems with Dox loaded via electrostatic interactions showed the lowest IC 50 and highest cellular internalization, indicating the pre-eminence of this interaction in Dox loading. The blank formulations are biocompatible and did not show cytotoxicity up to 0.17 mg/mL. The new functionalized star block copolymers based on cholic acid show great potential as drug delivery carriers.

PLGA/liposome hybrid nanoparticles for short-chain ceramide delivery.

PubMed

Zou, Peng; Stern, Stephan T; Sun, Duxin

2014-03-01

Rapid premature release of lipophilic drugs from liposomal lipid bilayer to plasma proteins and biological membranes is a challenge for targeted drug delivery. The purpose of this study is to reduce premature release of lipophilic short-chain ceramides by encapsulating ceramides into liposomal aqueous interior with the aid of poly (lactic-coglycolicacid) (PLGA). BODIPY FL labeled ceramide (FL-ceramide) and BODIPY-TR labeled ceramide (TR-ceramide) were encapsulated into carboxy-terminated PLGA nanoparticles. The negatively charged PLGA nanoparticles were then encapsulated into cationic liposomes to obtain PLGA/liposome hybrids. As a control, FL-ceramide and/or TR ceramide co-loaded liposomes without PLGA were prepared. The release of ceramides from PLGA/liposome hybrids and liposomes in rat plasma, cultured MDA-MB-231 cells, and rat blood circulation was compared using fluorescence resonance energy transfer (FRET) between FL-ceramide (donor) and TR-ceramide (acceptor). FRET analysis showed that FL-ceramide and TR-ceramide in liposomal lipid bilayer were rapidly released during incubation with rat plasma. In contrast, the FL-ceramide and TR-ceramide in PLGA/liposome hybrids showed extended release. FRET images of cells revealed that ceramides in liposomal bilayer were rapidly transferred to cell membranes. In contrast, ceramides in PLGA/liposome hybrids were internalized into cells with nanoparticles simultaneously. Upon intravenous administration to rats, ceramides encapsulated in liposomal bilayer were completely released in 2 min. In contrast, ceramides encapsulated in the PLGA core were retained in PLGA/liposome hybrids for 4 h. The PLGA/liposome hybrid nanoparticles reduced in vitro and in vivo premature release of ceramides and offer a viable platform for targeted delivery of lipophilic drugs.

Erlotinib-loaded albumin nanoparticles: A novel injectable form of erlotinib and its in vivo efficacy against pancreatic adenocarcinoma ASPC-1 and PANC-1 cell lines.

PubMed

Noorani, M; Azarpira, N; Karimian, K; Heli, H

2017-10-05

Erlotinib was loaded on albumin nanoparticles for the first time and the cytotoxic effect of the resulting nanoparticles against ASPC-1 and PANC-1 pancreatic adenocarcinoma cell lines was evaluated. The carrier (albumin nanoparticles, ANPs) was synthesized by desolvation method using a mixed solvent followed by thermal crosslinking for stabilization. ANPs and the drug-loaded ANPs were characterized by field emission scanning and transmission electron microscopies, particle size analysis and Fourier transform infrared spectroscopy. The nanoformulation had a size of <14nm with a good monodispersity. Drug loading and encapsulation efficiencies were evaluated as 27 and 44%. Cytotoxicity assays after 72h revealed the potential of ANPs to improve erlotinib toxicity (54% against 34% of free drug toward ASPC-1 cell line, and 52% against 30% toward PANC-1 cell line). Values of IC 50 were obtained for both cell lines and indicated significant reduction in the erlotinib dose necessary for killing the cells, while, ANPs were completely safe. The results demonstrated that erlotinib-loaded ANPs had a remarkable potential for pancreatic cancer drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Human Albumin Fragments Nanoparticles as PTX Carrier for Improved Anti-cancer Efficacy

PubMed Central

Ge, Liang; You, Xinru; Huang, Jun; Chen, Yuejian; Chen, Li; Zhu, Ying; Zhang, Yuan; Liu, Xiqiang; Wu, Jun; Hai, Qian

2018-01-01

For enhanced anti-cancer performance, human serum albumin fragments (HSAFs) nanoparticles (NPs) were developed as paclitaxel (PTX) carrier in this paper. Human albumins were broken into fragments via degradation and crosslinked by genipin to form HSAF NPs for better biocompatibility, improved PTX drug loading and sustained drug release. Compared with crosslinked human serum albumin NPs, the HSAF-NPs showed relative smaller particle size, higher drug loading, and improved sustained release. Cellular and animal results both indicated that the PTX encapsulated HSAF-NPs have shown good anti-cancer performance. And the anticancer results confirmed that NPs with fast cellular internalization showed better tumor inhibition. These findings will not only provide a safe and robust drug delivery NP platform for cancer therapy, but also offer fundamental information for the optimal design of albumin based NPs. PMID:29946256

Lipid encapsulation of arsenic trioxide attenuates cytotoxicity and allows for controlled anticancer drug release.

PubMed

Chen, Haimei; MacDonald, Robert C; Li, Shuyou; Krett, Nancy L; Rosen, Steven T; O'Halloran, Thomas V

2006-10-18

Arsenic trioxide (ATO, As2O3) is emerging as a front line agent for treatment of acute promyelocytic leukemia with giving a complete remission rate of 83-95%. ATO also shows significant activity in relapsed/refactory multiple myeloma; however, efforts to expand clinical utility to other cancers have been limited by its toxicity profile at higher doses. New bioavailable, liposome encapsulated As(III) materials exhibit a significantly attenuated cytotoxicity that undergoes pH-triggered release of an active drug. The arsenic drugs are loaded into 100-nm-scale liposomes at high concentration (>270 mM) and excellent retention (shelf life > 6 months at 4 degrees C), as determined by inductively coupled plasma optical emission spectroscopy (ICP-OES), transmission electron microscopy (TEM), and energy-dispersive X-ray (EDX) diffraction. In the loading mechanism, arsenous acid crosses the bilayer membrane in exchange for acetic acid and an insoluble transitional metal (e.g., Ni2+, Co2+) arsenite salt is formed. The resultant liposomal arsenic nanoparticles appear to be stable in physiological situations but release the drug cargo in a lower pH environment, as encountered in intracellular endosomes. These drugs exhibit attenuated cytotoxicities against human lymphoma tumor cells compared with that of free As2O3. Controlled release of arsenic drugs, and hence control of toxicity, is feasible with this system. The results demonstrate that cytotoxicity can be controlled via transitions of the inorganic drug between solid and solution phases and suggest a mechanism for further improvement of the risk/benefit ratio of As2O3 in treatment of a variety of cancers.

Hydrazone linked doxorubicin-PLA prodrug nanoparticles with high drug loading

NASA Astrophysics Data System (ADS)

Gatti, Simone; Agostini, Azzurra; Capasso Palmiero, Umberto; Colombo, Claudio; Peviani, Marco; Biffi, Alessandra; Moscatelli, Davide

2018-07-01

An optimal drug delivery system should be characterized by biocompatibility, biodegradability, high drug loading and favorable drug release profile. To achieve this goal a hydrazone linked doxorubicin-poly(lactic acid) prodrug (PLA-DOX) was synthesized by the functionalization of a short polymer chain produced by ring opening polymerization. The hydrophobic prodrug generated in this way was nanoprecipitated using a block copolymer to form polymeric nanoparticles (NPs) with a quantitative loading efficiency and a high and tunable drug loading. The effects of the concentration of the PLA-DOX prodrug and surfactant were studied by dynamic light scattering showing a range of NP size between 50 and 90 nm and monodispersed size distributions with polydispersity indexes lower then 0.27 up to a maximum DOX concentration of 27% w/w. The release profile of DOX from these NPs, tested at different pH conditions, showed a higher release rate in acidic conditions, consistent with the nature of the hydrazone bond which was used to conjugate the drug to the polymer. In vitro cytotoxicity studies performed on BV2 microglia-like cell line highlighted a specific cytotoxic effect of these NPs suggesting the maintenance of the drug efficacy and a modified release profile upon encapsulation of DOX in the NPs.

A poly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles

PubMed Central

Mert, Olcay; Lai, Samuel K.; Ensign, Laura; Yang, Ming; Wang, Ying-Ying; Wood, Joseph; Hanes, Justin

2011-01-01

Mucosal surfaces are protected by a highly viscoelastic and adhesive mucus layer that traps most foreign particles, including conventional drug and gene carriers. Trapped particles are eliminated on the order of seconds to hours by mucus clearance mechanisms, precluding sustained and targeted drug and nucleic acid delivery to mucosal tissues. We have previously shown that polymeric coatings that minimize adhesive interactions with mucus constituents lead to particles that rapidly penetrate human mucus secretions. Nevertheless, a particular challenge in formulating drug-loaded mucus penetrating particles (MPP) is that many commonly used surfactants are either mucoadhesive, or do not facilitate efficient drug encapsulation. We tested a novel surfactant molecule for particle formulation composed of Vitamin E conjugated to 5 kDa polyethylene glycol (VP5k). We show that VP5k-coated poly(lactide-co-glycolide) (PLGA) nanoparticles rapidly penetrate human cervicovaginal mucus, whereas PLGA nanoparticles coated with polyvinyl alcohol or Vitamin E conjugated to 1 kDa PEG were trapped. Importantly, VP5k facilitated high loading of paclitaxel, a frontline chemo drug, into PLGA MPP, with controlled release for at least 4 days and negligible burst release. Our results offer a promising new method for engineering biodegradable, drug-loaded MPP for sustained and targeted delivery of therapeutics at mucosal surfaces. PMID:21911015

Rational Design of Multifunctional Polymeric Nanoparticles Based on Poly(l-histidine) and d-α-Vitamin E Succinate for Reversing Tumor Multidrug Resistance.

PubMed

Li, Zhen; Chen, Qixian; Qi, Yan; Liu, Zhihao; Hao, Tangna; Sun, Xiaoxin; Qiao, Mingxi; Ma, Xiaodong; Xu, Ting; Zhao, Xiuli; Yang, Chunrong; Chen, Dawei

2018-04-11

A multifunctional nanoparticulate system composed of methoxy poly(ethylene glycol)-poly(l-histidine)-d-α-vitamin E succinate (MPEG-PLH-VES) copolymers for encapsulation of doxorubicin (DOX) was elaborated with the aim of circumventing the multidrug resistance (MDR) in breast cancer treatment. The MPEG-PLH-VES nanoparticles (NPs) were subsequently functionalized with biotin motif for targeted drug delivery. The MPEG-PLH-VES copolymer exerts no obvious effect on the P-gp expression level of MCF-7/ADR but exhibited a significant influence on the loss of mitochondrial membrane potential, the reduction of intracellular ATP level, and the inhibition of P-gp ATPase activity of MCF-7/ADR cells. The constructed MPEG-PLH-VES NPs exhibited an acidic pH-induced increase on particle size in aqueous solution. The DOX-encapsulated MPEG-PLH-VES/biotin-PEG-VES (MPEG-PLH-VES/B) NPs were characterized to possess high drug encapsulation efficiency of approximate 90%, an average particle size of approximately 130 nm, and a pH-responsive drug release profile in acidic milieu. Confocal laser scanning microscopy (CLSM) investigations revealed that the DOX-loaded NPs resulted in an effective delivery of DOX into MCF-/ADR cells and a notable carrier-facilitated escape from endolysosomal entrapment. Pertaining to the in vitro cytotoxicity evaluation, the DOX-loaded MPEG-PLH-VES/B NPs resulted in more pronounced cytotoxicity to MCF-/ADR cells compared with DOX-loaded MPEG-PLH-VES NPs and free DOX solution. In vivo imaging study in MCF-7/ADR tumor-engrafted mice exhibited that the MPEG-PLH-VES/B NPs accumulated at the tumor site more effectively than MPEG-PLH-VES NPs due to the biotin-mediated active targeting effect. In accordance with the in vitro results, DOX-loaded MPEG-PLH-VES/B NPs showed the strongest inhibitory effect against the MCF-7/ADR xenografted tumors with negligible systemic toxicity, as evidenced by the histological analysis and change of body weight. The multifunctional MPEG-PLH-VES/B nanoparticulate system has been demonstrated to provide a promising strategy for efficient delivery of DOX into MCF-7/ADR cancerous cells and reversing MDR.

Nanostructured delivery system for Suberoylanilide hydroxamic acid against lung cancer cells.

PubMed

Sankar, Renu; Karthik, Selvaraju; Subramanian, Natesan; Krishnaswami, Venkateshwaran; Sonnemann, Jürgen; Ravikumar, Vilwanathan

2015-06-01

With the objective to provide a potential approach for the treatment of lung cancer, nanotechnology based Suberoylanilide hydroxamic acid (SAHA)-loaded Poly-d, l-lactide-co glycolide (PLGA) nanoparticles have been formulated using the nanoprecipitation technique. The acquired nanoparticles were characterized by various throughput techniques and the analyses showed the presence of smooth and spherical shaped SAHA-loaded PLGA nanoparticles, with an encapsulation efficiency of 44.8% and a particle size of 208nm. The compatibility between polymer and drug in the formulation was tested using FT-IR, Micro-Raman spectrum and DSC thermogram analyses, revealing a major interaction between the drug and polymer. The in vitro drug release from the SAHA-loaded PLGA nanoparticles was found to be biphasic with an initial burst followed by a sustained release for up to 50h. In experiments using the lung cancer cell line A549, SAHA-loaded PLGA nanoparticles demonstrated a superior antineoplastic activity over free SAHA. In conclusion, SAHA-loaded PLGA nanoparticles may be a useful novel approach for the treatment of lung cancer. Copyright © 2015. Published by Elsevier B.V.

Doxorubicin loaded magnetic polymersomes: theranostic nanocarriers for MR imaging and magneto-chemotherapy.

PubMed

Sanson, Charles; Diou, Odile; Thévenot, Julie; Ibarboure, Emmanuel; Soum, Alain; Brûlet, Annie; Miraux, Sylvain; Thiaudière, Eric; Tan, Sisareuth; Brisson, Alain; Dupuis, Vincent; Sandre, Olivier; Lecommandoux, Sébastien

2011-02-22

Hydrophobically modified maghemite (γ-Fe(2)O(3)) nanoparticles were encapsulated within the membrane of poly(trimethylene carbonate)-b-poly(l-glutamic acid) (PTMC-b-PGA) block copolymer vesicles using a nanoprecipitation process. This formation method gives simple access to highly magnetic nanoparticles (MNPs) (loaded up to 70 wt %) together with good control over the vesicles size (100-400 nm). The simultaneous loading of maghemite nanoparticles and doxorubicin was also achieved by nanoprecipitation. The deformation of the vesicle membrane under an applied magnetic field has been evidenced by small angle neutron scattering. These superparamagnetic hybrid self-assemblies display enhanced contrast properties that open potential applications for magnetic resonance imaging. They can also be guided in a magnetic field gradient. The feasibility of controlled drug release by radio frequency magnetic hyperthermia was demonstrated in the case of encapsulated doxorubicin molecules, showing the viability of the concept of magneto-chemotherapy. These magnetic polymersomes can be used as efficient multifunctional nanocarriers for combined therapy and imaging.

Combined image guided monitoring the pharmacokinetics of rapamycin loaded human serum albumin nanoparticles with a split luciferase reporter

NASA Astrophysics Data System (ADS)

Wang, Fu; Yang, Kai; Wang, Zhe; Ma, Ying; Gutkind, J. Silvio; Hida, Naoki; Niu, Gang; Tian, Jie

2016-02-01

Imaging guided techniques have been increasingly employed to investigate the pharmacokinetics (PK) and biodistribution of nanoparticle based drug delivery systems. In most cases, however, the PK profiles of drugs could vary significantly from those of drug delivery carriers upon administration in the blood circulation, which complicates the interpretation of image findings. Herein we applied a genetically encoded luciferase reporter in conjunction with near infrared (NIR) fluorophores to investigate the respective PK profiles of a drug and its carrier in a biodegradable drug delivery system. In this system, a prototype hydrophobic agent, rapamycin (Rapa), was encapsulated into human serum albumin (HSA) to form HSA Rapa nanoparticles, which were then labeled with Cy5 fluorophore to facilitate the fluorescence imaging of HSA carrier. Meanwhile, we employed transgenetic HN12 cells that were modified with a split luciferase reporter, whose bioluminescence function is regulated by Rapa, to reflect the PK profile of the encapsulated agent. It was interesting to discover that there existed an obvious inconsistency of PK behaviors between HSA carrier and rapamycin in vitro and in vivo through near infrared fluorescence imaging (NIFRI) and bioluminescence imaging (BLI) after treatment with Cy5 labeled HSA Rapa. Nevertheless, HSA Rapa nanoparticles manifested favorable in vivo PK and tumor suppression efficacy in a follow-up therapeutic study. The developed strategy of combining a molecular reporter and a fluorophore in this study could be extended to other drug delivery systems to provide profound insights for non-invasive real-time evaluation of PK profiles of drug-loaded nanoparticles in pre-clinical studies.Imaging guided techniques have been increasingly employed to investigate the pharmacokinetics (PK) and biodistribution of nanoparticle based drug delivery systems. In most cases, however, the PK profiles of drugs could vary significantly from those of drug delivery carriers upon administration in the blood circulation, which complicates the interpretation of image findings. Herein we applied a genetically encoded luciferase reporter in conjunction with near infrared (NIR) fluorophores to investigate the respective PK profiles of a drug and its carrier in a biodegradable drug delivery system. In this system, a prototype hydrophobic agent, rapamycin (Rapa), was encapsulated into human serum albumin (HSA) to form HSA Rapa nanoparticles, which were then labeled with Cy5 fluorophore to facilitate the fluorescence imaging of HSA carrier. Meanwhile, we employed transgenetic HN12 cells that were modified with a split luciferase reporter, whose bioluminescence function is regulated by Rapa, to reflect the PK profile of the encapsulated agent. It was interesting to discover that there existed an obvious inconsistency of PK behaviors between HSA carrier and rapamycin in vitro and in vivo through near infrared fluorescence imaging (NIFRI) and bioluminescence imaging (BLI) after treatment with Cy5 labeled HSA Rapa. Nevertheless, HSA Rapa nanoparticles manifested favorable in vivo PK and tumor suppression efficacy in a follow-up therapeutic study. The developed strategy of combining a molecular reporter and a fluorophore in this study could be extended to other drug delivery systems to provide profound insights for non-invasive real-time evaluation of PK profiles of drug-loaded nanoparticles in pre-clinical studies. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07308a

Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma

PubMed Central

Civallero, Monica; Citti, Cinzia; Cosenza, Maria; Baldassarre, Francesca; Cannazza, Giuseppe; Pozzi, Samantha; Sacchi, Stefano

2018-01-01

Owing to their nano-sized porous structure, CaCO3 nanocrystals (CaCO3NCs) hold the promise to be utilized as desired materials for encapsulating molecules which demonstrate wide promise in drug delivery. We evaluate the possibility to encapsulate and release NVP-BEZ235, a novel and potent dual PI3K/mTOR inhibitor that is currently in phase I/II clinical trials for advanced solid tumors, from the CaCO3NCs. Its chemical nature shows some intrinsic limitations which induce to administer high doses leading to toxicity; to overcome these problems, here we proposed a strategy to enhance its intracellular penetration and its biological activity. Pristine CaCO3 NCs biocompatibility, cell interactions and internalization in in vitro experiments on T-cell lymphoma line, were studied. Confocal microscopy was used to monitor NCs-cell interactions and cellular uptake. We have further investigated the interaction nature and release mechanism of drug loaded/released within/from the NCs using an alternative approach based on liquid chromatography coupled to mass spectrometry. Our approach provides a good loading efficiency, therefore this drug delivery system was validated for biological activity in T-cell lymphoma: the anti-proliferative test and western blot results are very interesting because the proposed nano-formulation has an efficiency higher than free drug at the same nominal concentration. PMID:29370086

Formulation, characterization and evaluation of cyclodextrin-complexed bendamustine-encapsulated PLGA nanospheres for sustained delivery in cancer treatment.

PubMed

Gidwani, Bina; Vyas, Amber

2016-03-01

PLGA nanospheres are considered to be promising drug carrier in the treatment of cancer. Inclusion complex of bendamustine (BM) with epichlorohydrin beta cyclodextrin polymer was prepared by freeze-drying method. Phase solubility study revealed formation of AL type complex with stability constant (Ks = 645 M(-1)). This inclusion complex was encapsulated into PLGA nanospheres using solid-in-oil-in-water (S/O/W) technique. The particle size and zeta potential of PLGA nanospheres loaded with cyclodextrin-complexed BM were about 151.4 ± 2.53 nm and - 31.9 ± (-3.08) mV. In-vitro release study represented biphasic release pattern with 20% burst effect and sustained slow release. DSC studies indicated that inclusion complex incorporated in PLGA nanospheres was not in a crystalline state but existed in an amorphous or molecular state. The cytotoxicity experiment was studied in Z-138 cells and IC50 value was found to be 4.3 ± 0.11 µM. Cell viability studies revealed that the PLGA nanospheres loaded with complex exerts a more pronounced effect on the cancer cells as compared to the free drug. In conclusion, PLGA nanospheres loaded with inclusion complex of BM led to sustained drug delivery. The nanospheres were stable after 3 months of storage conditions with slight change in their particle size, zeta potential and entrapment efficiency.

Techniques for Loading Technetium-99m and Rhenium-186/188 Radionuclides into Preformed Liposomes for Diagnostic Imaging and Radionuclide Therapy.

PubMed

Goins, Beth; Bao, Ande; Phillips, William T

2017-01-01

Liposomes can serve as carriers of radionuclides for diagnostic imaging and therapeutic applications. Herein, procedures are outlined for radiolabeling liposomes with the gamma-emitting radionuclide, technetium-99m ( 99m Tc), for noninvasive detection of disease and for monitoring the pharmacokinetics and biodistribution of liposomal drugs, and/or with therapeutic beta-emitting radionuclides, rhenium-186/188 ( 186/188 Re), for radionuclide therapy. These efficient and practical liposome radiolabeling methods use a post-labeling mechanism to load 99m Tc or 186/188 Re into preformed liposomes prepared in advance of the labeling procedure. For all liposome radiolabeling methods described, a lipophilic chelator is used to transport 99m Tc or 186/188 Re across the lipid bilayer of the preformed liposomes. Once within the liposome interior, the pre-encapsulated glutathione or ammonium sulfate (pH) gradient provides for stable entrapment of the 99m Tc and 186/188 Re within the liposomes. In the first method, 99m Tc is transported across the lipid bilayer by the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO) and 99m Tc-HMPAO becomes trapped by interaction with the pre-encapsulated glutathione within the liposomes. In the second method, 99m Tc or 186/188 Re is transported across the lipid bilayer by the lipophilic chelator, N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), and 99m Tc-BMEDA or 186/188 Re-BMEDA becomes trapped by interaction with pre-encapsulated glutathione within the liposomes. In the third method, an ammonium sulfate (pH) gradient loading technique is employed using liposomes with an extraliposomal pH of 7.4 and an interior pH of 5.1. BMEDA, which is lipophilic at pH 7.4, serves as a lipophilic chelator for 99m Tc or 186/188 Re to transport the radionuclides across the lipid bilayer. Once within the more acidic liposome interior, 99m Tc/ 186/188 Re-BMEDA complex becomes protonated and more hydrophilic, which results in stable entrapment of the 99m Tc/ 186/188 Re-BMEDA complex within the liposomes. Since many commercially available liposomal drugs use an ammonium sulfate (pH) gradient for drug loading, these liposomal drugs can be directly radiolabeled with 99m Tc-BMEDA for noninvasive monitoring of tissue distribution during treatment or with 186/188 Re-BMEDA for combination chemo-radionuclide therapy.

Encapsulation of Curcumin in Self-Assembling Peptide Hydrogels as Injectable Drug Delivery Vehicles

PubMed Central

Altunbas, Aysegul; Lee, Seung Joon; Rajasekaran, Sigrid A.; Schneider, Joel P.; Pochan, Darrin J.

2011-01-01

Curcumin, a hydrophobic polyphenol, is an extract of turmeric root with antioxidant, anti-inflammatory and anti-tumorigenic properties. Its lack of water solubility and relatively low bioavailability set major limitations for its therapeutic use. In this study, a self-assembling peptide hydrogel is demonstrated to be an effective vehicle for the localized delivery of curcumin over sustained periods of time. The curcumin-hydrogel is prepared in-situ where curcumin encapsulation within the hydrogel network is accomplished concurrently with peptide self-assembly. Physical and in vitro biological studies were used to demonstrate the effectiveness of curcumin-loaded β-hairpin hydrogels as injectable agents for localized curcumin delivery. Notably, rheological characterization of the curcumin loaded hydrogel before and after shear flow have indicated solid-like properties even at high curcumin payloads. In vitro experiments with a medulloblastoma cell line confirm that the encapsulation of the curcumin within the hydrogel does not have an adverse effect on its bioactivity. Most importantly, the rate of curcumin release and its consequent therapeutic efficacy can be conveniently modulated as a function of the concentration of the MAX8 peptide. PMID:21601921

Engineering of layered, lipid-encapsulated drug nanoparticles through spray-drying.

PubMed

Sapra, Mahak; Mayya, Y S; Venkataraman, Chandra

2017-06-01

Drug-containing nanoparticles have been synthesized through the spray-drying of submicron droplet aerosols by using matrix materials such as lipids and biopolymers. Understanding layer formation in composite nanoparticles is essential for the appropriate engineering of particle substructures. The present study developed a droplet-shrinkage model for predicting the solid-phase formation of two non-volatile solutes-stearic acid lipid and a set of drugs, by considering molecular volume and solubility. Nanoparticle formation was simulated to define the parameter space of material properties and process conditions for the formation of a layered structure with the preferential accumulation of the lipid in the outer layer. Moreover, lipid-drug demarcation diagrams representing a set of critical values of ratios of solute properties at which the two solutes precipitate simultaneously were developed. The model was validated through the preparation of stearic acid-isoniazid nanoparticles under controlled processing conditions. The developed model can guide the selection of solvents, lipids, and processing conditions such that drug loading and lipid encapsulation in composite nanoparticles are optimized. Copyright © 2017 Elsevier B.V. All rights reserved.

Sustained release of methotrexate through liquid-crystalline folate nanoparticles.

PubMed

Misra, Rahul; Mohanty, Sanat

2014-09-01

To make chemotherapy more effective, sustained release of the drug is desirable. By controlling the release rates, constant therapeutic levels can be achieved which can avoid re-administration of drug. This helps to combat tumors more effectively with minimal side effects. The present study reports the control release of methotrexate through liquid-crystalline folate nanoparticles. These nanoparticles are composed of highly ordered folate self-assembly which encapsulate methotrexate molecules. These drug molecules can be released in a controlled manner by disrupting this assembly in the environment of monovalent cations. The ordered structure of folate nanoparticles offers low drug losses of about 4-5%, which is significant in itself. This study reports the size-control method of forming methotrexate encapsulated folate nanoparticles as well as the release of methotrexate through these nanoparticles. It has been demonstrated that methotrexate release rates can be controlled by controlling the size of the nanoparticles, cross-linking cation and cross-linking concentration. The effect of different factors like drug loading, release medium, and pH of the medium on methotrexate release rates was also studied.

Comparative studies on the properties of glycyrrhetinic acid-loaded PLGA microparticles prepared by emulsion and template methods.

PubMed

Wang, Hong; Zhang, Guangxing; Sui, Hong; Liu, Yanhua; Park, Kinam; Wang, Wenping

2015-12-30

The O/W emulsion method has been widely used for the production of poly (lactide-co-glycolide) (PLGA) microparticles. Recently, a template method has been used to make homogeneous microparticles with predefined size and shape, and shown to be useful in encapsulating different types of active compounds. However, differences between the template method and emulsion method have not been examined. In the current study, PLGA microparticles were prepared by the two methods using glycyrrhetinic acid (GA) as a model drug. The properties of obtained microparticles were characterized and compared on drug distribution, in vitro release, and degradation. An encapsulation efficiency of over 70% and a mean particle size of about 40μm were found for both methods. DSC thermograms and XRPD diffractograms indicated that GA was highly dispersed or in the amorphous state in the matrix of microparticles. The emulsion method produced microparticles of a broad size distribution with a core-shell type structure and many drug-rich domains inside each microparticle. Its drug release and matrix degradation was slow before Day 50 and then accelerated. In contrast, the template method formed microparticles with narrow size distribution and drug distribution without apparent drug-rich domains. The template microparticles with a loading efficiency of 85% exhibited a zero-order release profile for 3 months after the initial burst release of 26.7%, and a steady surface erosion process as well. The same microparticles made by two different methods showed two distinguished drug release profiles. The two different methods can be supplementary with each other in optimization of drug formulation for achieving predetermined drug release patterns. Copyright © 2015 Elsevier B.V. All rights reserved.

Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for oral delivery of acyclovir.

PubMed

Gourdon, Betty; Chemin, Caroline; Moreau, Amélie; Arnauld, Thomas; Baumy, Philippe; Cisternino, Salvatore; Péan, Jean-Manuel; Declèves, Xavier

2017-08-30

Targeting intestinal di- and tri-peptide transporter PepT1 with prodrugs is a successful strategy to improve oral drug bioavailability, as demonstrated with valacyclovir, a prodrug of acyclovir. The aim of this new drug delivery strategy is to over-concentrate a poorly absorbed drug on the intestinal membrane surface by targeting PepT1 with functionalized polymer nanoparticles. In the present study, poly(lactic acid)-poly(ethylene glycol)-ligand (PLA-PEG-ligand) nanoparticles were obtained by nanoprecipitation. A factorial experimental design allowed us to identify size-influent parameters and to obtain optimized ≈30nm nanoparticles. Valine, Glycylsarcosine, Valine-Glycine, and Tyrosine-Valine were chemically linked to PLA-PEG. In Caco-2 cell monolayer model, competition between functionalized nanoparticles and [ 3 H]Glycylsarcosine, a strong substrate of PepT1, reduced [ 3 H]Glycylsarcosine transport from 22 to 46%. Acyclovir was encapsulated with a drug load of ≈10% in valine-functionalized nanoparticles, resulting in a 2.7-fold increase in permeability as compared to the free drug. An in vivo pharmacokinetic study in mice compared oral absorption of acyclovir after administration of 25mg/kg of valacyclovir, free or encapsulated acyclovir in functionalized nanoparticles. Acyclovir encapsulation did not statistically modify AUC or C max , but increased t 1/2 and MRT 1.3-fold as compared to free acyclovir. This new strategy is promising for poorly absorbed drugs by oral administration. Copyright © 2017 Elsevier B.V. All rights reserved.

Curcumin-Loading-Dependent Stability of PEGMEMA-Based Micelles Affects Endocytosis and Exocytosis in Colon Carcinoma Cells.

PubMed

Chang, Teddy; Trench, David; Putnam, Joshua; Stenzel, Martina H; Lord, Megan S

2016-03-07

Polymeric micelles were formed from poly(poly(ethylene glycol) methyl ether methacrylate)-block-poly(styrene) (P(PEGMEMA)-b-PS) block copolymer of two different chain lengths. The micelles formed were approximately 16 and 46 nm in diameter and used to encapsulate curcumin. Upon loading of the curcumin into the micelles, their size increased to approximately 34 and 80 nm in diameter, respectively, with a loading efficiency of 58%. The unloaded micelles were not cytotoxic to human colon carcinoma cells, whereas only the smaller loaded micelles were cytotoxic after 72 h of exposure. The micelles were rapidly internalized by the cells within minutes of exposure, with the loaded micelles internalized to a greater extent owing to their enhanced stability compared to that of the unloaded micelles. The larger micelles were more rapidly internalized and exocytosed than the smaller micelles, demonstrating the effect of micelle size and drug loading on drug delivery and cytotoxicity.

Liposome encapsulated berberine treatment attenuates cardiac dysfunction after myocardial infarction.

PubMed

Allijn, Iris E; Czarny, Bertrand M S; Wang, Xiaoyuan; Chong, Suet Yen; Weiler, Marek; da Silva, Acarilia Eduardo; Metselaar, Josbert M; Lam, Carolyn Su Ping; Pastorin, Giorgia; de Kleijn, Dominique P V; Storm, Gert; Wang, Jiong-Wei; Schiffelers, Raymond M

2017-02-10

Inflammation is a known mediator of adverse ventricular remodeling after myocardial infarction (MI) that may lead to reduction of ejection fraction and subsequent heart failure. Berberine is a isoquinoline quarternary alkaloid from plants that has been associated with anti-inflammatory, anti-oxidative, and cardioprotective properties. Its poor solubility in aqueous buffers and its short half-life in the circulation upon injection, however, have been hampering the extensive usage of this natural product. We hypothesized that encapsulation of berberine into long circulating liposomes could improve its therapeutic availability and efficacy by protecting cardiac function against MI in vivo. Berberine-loaded liposomes were prepared by ethanol injection and characterized. They contained 0.3mg/mL of the drug and were 0.11μm in diameter. Subsequently they were tested for IL-6 secretion inhibition in RAW 264.7 macrophages and for cardiac function protection against adverse remodeling after MI in C57BL/6J mice. In vitro, free berberine significantly inhibited IL-6 secretion (IC 50 =10.4μM), whereas encapsulated berberine did not as it was not released from the formulation in the time frame of the in vitro study. In vivo, berberine-loaded liposomes significantly preserved the cardiac ejection fraction at day 28 after MI by 64% as compared to control liposomes and free berberine. In conclusion, liposomal encapsulation enhanced the solubility of berberine in buffer and preserves ejection fraction after MI. This shows that delivery of berberine-loaded liposomes significantly improves its therapeutic availability and identifies berberine-loaded liposomes as potential treatment of adverse remodeling after MI. Copyright © 2017 Elsevier B.V. All rights reserved.

The enhanced longevity and liver targetability of Paclitaxel by hybrid liposomes encapsulating Paclitaxel-conjugated gold nanoparticles.

PubMed

Bao, Quan-Ying; Zhang, Ning; Geng, Dong-Dong; Xue, Jing-Wei; Merritt, Mackenzie; Zhang, Can; Ding, Ya

2014-12-30

Organic and inorganic drug delivery systems both demonstrate their own advantages and challenges in practical applications. Combining these two drug delivery strategies in one system is expected to solve their current issues and achieve desirable functions. In this paper, gold nanoparticles (GNPs) and liposomes have been chosen as the model systems to construct a hybrid system and investigate its performance for the tumor therapy of Paclitaxel (PTX). The thiol-terminated polyethylene glycol (PEG400)-PTX derivative has been covalently modified on the surface of GNPs, followed by the encapsulation of PTX-conjugated GNPs (PTX-PEG400@GNPs) in liposomes. The hybrid liposomes solve the solubility and stability problems of gold conjugates and show high drug loading capacity. In vitro PTX release from the hybrid system maintains the similar sustained behavior demonstrated in its conjugates. Under the protection of a biocompatible liposome shell, encapsulated PTX shows enhanced circulation longevity and liver targetability compared to Taxol(®) and PTX-PEG400@GNPs suspension in the pharmacokinetic and biodistribution studies. These indicate that encapsulating drug-conjugated inorganic nanoparticles inside organic carriers maintains the superiority of both vehicles and improves the performance of hybrid systems. Although these attributes of hybrid liposomes lead to a better therapeutic capacity in a murine liver cancer model than that of the comparison groups, it shows no significant difference from Taxol(®) and conjugate suspension. This result could be due to the delayed and sustained drug release from the system. However, it indicates the promising potential for these hybrid liposomes will allow further construction of a compound preparation with improved performance that is based on their enhanced longevity and liver targetability of Paclitaxel. Copyright © 2014 Elsevier B.V. All rights reserved.

Sustained Release of Green Tea Polyphenols from Liposomal Nanoparticles; Release Kinetics and Mathematical Modelling.

PubMed

Prakash Upputuri, Ravi Theaj; Azad Mandal, Abul Kalam

2017-01-01

Background: Green tea polyphenols (GTP) are known to have several health benefits. In spite of these benefits, its application as a therapeutic agent is limited due to some of its limitations such as stability, bioavailability, and biotransformation. To overcome these limitations, liposomal nanoparticles have been used as a carrier of the GTP. Objective: Encapsulation of GTP to the liposomal nanoparticles in order to achieve a sustained release of the GTP and to determine the drug release kinetics and the mechanism of the release. Materials and Methods: GTP encapsulated liposomal nanoparticles were prepared using phosphatidyl choline and cholesterol. The synthesized particles were characterized for their particle size and morphology. In vitro release studies were carried out, followed by drug release kinetics, and determining the mechanism of release. In vitro , antioxidant assay was determined following 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Results: Atomic force microscope (AFM) and high resolution scanning electron microscope (HR SEM) images showed spherical particles of the size of 64.5 and 252 nm. An encapsulation efficiency as high as 77.7% was observed with GTP concentration of 5 mg.mL -1 . In vitro release studies showed that the loading concentrations of GTP were independent to the cumulative percentage of the drug release. GTP release by varying the pH and temperature showed a direct correlation between the release parameter and the percentage of drug release. The higher the pH and temperature, the higher was the percentage of the drug release. The release data showed a good correlation with Zero order kinetics and the mechanism of the release being anomalous mode. Radical scavenging activity of the released GTP showed a potent scavenging activity. Conclusion: GTP encapsulated liposomal nanoparticles could be used as a delivery vehicle for achieving a sustained release.

High hydrostatic pressure encapsulation of doxorubicin in ferritin nanocages with enhanced efficiency.

PubMed

Wang, Qi; Zhang, Chun; Liu, Liping; Li, Zenglan; Guo, Fangxia; Li, Xiunan; Luo, Jian; Zhao, Dawei; Liu, Yongdong; Su, Zhiguo

2017-07-20

Human ferritin (HFn) nanocaging is becoming an appealing platform for anticancer drugs delivery. However, protein aggregation always occurs during the encapsulation process, resulting in low production efficiency. A new approach using high hydrostatic pressure (HHP) was explored in this study to overcome the problem of loading doxorubicin (DOX) in HFn. At the pressure of 500MPa and pH 5.5, DOX molecules were found to be encapsulated into HFn. Meanwhile, combining it with an additive of 20mM arginine completely inhibited precipitation and aggregation, resulting in highly monodispersed nanoparticles with almost 100% protein recovery. Furthermore, stepwise decompression and incubation of the complex in atmospheric pressure at pH 7.4 for another period could further increase the DOX encapsulation ratio. The HFn-DOX nanoparticles (NPs) showed similar morphology and structural features to the hollow cage and no notable drug leakage occurred for HFn-DOX NPs when stored at 4°C and pH 7.4 for two weeks. HFn-DOX NPs prepared through HHP also showed significant cytotoxicity in vitro and higher antitumor bioactivity in vivo than naked DOX. Moreover, This HHP encapsulation strategy could economize on DOX that was greatly wasted during the conventional preparation process simply through a desalting column. These results indicated that HHP could offer a feasible approach with high efficiency for the production of HFn-DOX NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Structure of modified [epsilon]-polylysine micelles and their application in improving cellular antioxidant activity of curcuminoids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Hailong; Li, Ji; Shi, Ke

The micelle structure of octenyl succinic anhydride modified {var_epsilon}-polylysine (M-EPL), an anti-microbial surfactant prepared from natural peptide {var_epsilon}-polylysine in aqueous solution has been studied using synchrotron small-angle X-ray scattering (SAXS). Our results revealed that M-EPLs formed spherical micelles with individual size of 24-26 {angstrom} in aqueous solution which could further aggregate to form a larger dimension with averaged radius of 268-308 {angstrom}. Furthermore, M-EPL micelle was able to encapsulate curcuminoids, a group of poorly-soluble bioactive compounds from turmeric with poor oral bioavailability, and improve their water solubility. Three loading methods, including solvent evaporation, dialysis, and high-speed homogenization were compared. Themore » results indicated that the dialysis method generated the highest loading capacity and curcuminoids water solubility. The micelle encapsulation was confirmed as there were no free curcuminoid crystals detected in the differential scanning calorimetry analysis. It was also demonstrated that M-EPL encapsulation stabilized curcuminoids against hydrolysis at pH 7.4 and the encapsulated curcuminoids showed elevated cellular antioxidant activity compared with free curcuminoids. This work suggested that M-EPL could be used as new biopolymer micelles for delivering poorly soluble drugs/phytochemicals and improving their bioactivities.« less

[Preparation of scopolamine hydrobromide nanoparticles-in-microsphere system].

PubMed

Lü, Wei-ling; Hu, Jin-hong; Zhu, Quan-gang; Li, Feng-qian

2010-07-01

This study is to prepare scopolamine hydrobromide nanoparticles-in-microsphere system (SH-NiMS) and evaluate its drug release characteristics in vitro. SH nanoparticles were prepared by ionic crosslinking method with tripolyphosphate (TPP) as crosslinker and chitosan as carrier. Orthogonal design was used to optimize the formulation of SH nanoparticles, which took the property of encapsulation efficiency and drug loading as evaluation parameters. With HPMC as carrier, adjusted the parameters of spray drying technique and sprayed the SH nanoparticles in microspheres encaposulated by HPMC was formed and which is called nanoparticles-in-microsphere system (NiMS). SH-NiMS appearances were observed by SEM, structure was obsearved by FT-IR and the release characteristics in vitro were evaluated. The optimized formulation of SH nanoparticles was TPP/CS 1:3 (w/w), HPMC 0.3%, SH 0.2%. The solution peristaltic speed of the spray drying technique was adjusted to 15%, and the temperature of inlet was 110 degrees C. The encapsulation product yeild, drug loading and particle sizes of SH-NiMS were 94.2%, 20.4%, and 1256.5 nm, respectively. The appearances and the structure of SH-NiMS were good. The preparation method of SH-NiMS is stable and reliable to use, which provide a new way to develop new dosage form.

Lipid-drug-conjugate (LDC) solid lipid nanoparticles (SLN) for the delivery of nicotine to the oral cavity - optimization of nicotine loading efficiency.

PubMed

Ding, Yuan; Nielsen, Kent A; Nielsen, Bruno P; Bøje, Niels W; Müller, Rainer H; Pyo, Sung Min

2018-03-12

Nicotine, obtained from tobacco leaves, has been used to promote the cessation of smoking and reduce the risk of COPD and lung cancer. Incorporating the active in lipid nanoparticles is an effective tool to minimize its irritation potential and to use the particles as intermediate to produce final products. However, as a hydrophilic active, it is a challenge to prepare nicotine loaded lipid nanoparticles with high drug loading. In this study, lipid-drug-conjugates (LDC) were formed by nicotine and different fatty acids to enable the production of sufficiently loaded nicotine lipid nanoparticles. The encapsulation efficiency of nicotine in LDC-containing SLN was about 50%, which increased at least fourfold compared to the non-LDC formulations (around 10%) due to the increased lipophilicity of nicotine by strong interactions between positively charged nicotine and negatively charged fatty acids (formation of LDCs). The z-average of all formulations (150 to 350 nm) proved to be in the required submicron size range with a narrow size distribution. In summary, nicotine loaded LDC lipid nanoparticles with high drug loading were successfully developed with Kolliwax® S and stearic acid as counter-ion forming the LDC and hydrogenated sunflower oil (HSO) as lipid particle matrix. Copyright © 2018. Published by Elsevier B.V.

The Effect of Millisecond Pulsed Electric Fields (msPEF) on Intracellular Drug Transport with Negatively Charged Large Nanocarriers Made of Solid Lipid Nanoparticles (SLN): In Vitro Study.

PubMed

Kulbacka, Julita; Pucek, Agata; Wilk, Kazimiera Anna; Dubińska-Magiera, Magda; Rossowska, Joanna; Kulbacki, Marek; Kotulska, Małgorzata

2016-10-01

Drug delivery technology is still a dynamically developing field of medicine. The main direction in nanotechnology research (nanocarriers, nanovehicles, etc.) is efficient drug delivery to target cells with simultaneous drug reduction concentration. However, nanotechnology trends in reducing the carrier sizes to several nanometers limit the volume of the loaded substance and may pose a danger of uncontrolled access into the cells. On the other hand, nanoparticles larger than 200 nm in diameter have difficulties to undergo rapid diffusional transport through cell membranes. The main advantage of large nanoparticles is higher drug encapsulation efficiency and the ability to deliver a wider array of drugs. Our present study contributes a new approach with large Tween 80 solid lipid nanoparticles SLN (i.e., hydrodynamic GM-SLN-glycerol monostearate, GM, as the lipid and ATO5-SLNs-glyceryl palmitostearate, ATO5, as the lipid) with diameters DH of 379.4 nm and 547 nm, respectively. They are used as drug carriers alone and in combination with electroporation (EP) induced by millisecond pulsed electric fields. We evaluate if EP can support the transport of large nanocarriers into cells. The study was performed with two cell lines: human colon adenocarcinoma LoVo and hamster ovarian fibroblastoid CHO-K1 with coumarin 6 (C6) as a fluorescent marker for encapsulation. The biological safety of the potential treatment procedure was evaluated with cell viability after their exposure to nanoparticles and EP. The EP efficacy was evaluated by FACS method. The impact on intracellular structure organization of cytoskeleton was visualized by CLSM method with alpha-actin and beta-tubulin. The obtained results indicate low cytotoxicity of both carrier types, free and loaded with C6. The evaluation of cytoskeleton proteins indicated no intracellular structure damage. The intracellular uptake and accumulation show that SLNs do not support transport of C6 coumarin. Only application of electroporation improved the transport of encapsulated and free C6 into both treated cell lines.

Synthesis, characterization, and property of biodegradable PEG-PCL-PLA terpolymers with miktoarm star and triblock architectures as drug carriers.

PubMed

Zhang, Yixin; Luo, Song; Liang, Yan; Zhang, Hai; Peng, Xinyu; He, Bin; Li, Sai

2018-03-01

A series of amphiphilic terpolymers with miktoarm star and triblock architectures of poly(ethylene glycol) (PEG), poly(ε-caprolactone) (PCL) and poly(l-lactide acid) (PLLA) or poly(DL-lactide acid) (PDLLA) terpolymers were synthesized as carriers for drug delivery. The architecture, molecular weight and crystallization behavior of the terpolymers were characterized. Anticancer drug doxorubicin was encapsulated in the micelles to investigate their drug loading properties. The miktoarm star terpolymers exhibited stronger crystallization capability, smaller size and better stability than that of triblock polymeric micelle, owing to the lower CMC values of miktoarm star polymeric micelle. Furthermore, the drug-loaded miktoarm star polymeric micelles showed the cumulative DOX release account of the micelles with PDLLA blocks was 65.3% while the release account of the corresponding micelles containing PLLA blocks was 45.2%. The IC 50 values of drug-loaded miktoarm star polymeric micelle were lower than triblock polymeric micelle. Meanwhile, Confocal laser scanning microscopy (CLSM) and Flow Cytometry results demonstrated that the miktoarm star micelles were more favorable for cellular internalization. The miktoarm star micelles with PDLLA blocks were promising carriers for anticancer drug delivery.

Nanoengineered drug delivery systems for enhancing antibiotic therapy.

PubMed

Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

2015-03-01

Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Preparation and characterization of PLGA-β-CD polymeric nanoparticles containing methotrexate and evaluation of their effects on T47D cell line.

PubMed

Gorjikhah, Fatemeh; Azizi Jalalian, Farid; Salehi, Roya; Panahi, Yunes; Hasanzadeh, Arash; Alizadeh, Effat; Akbarzadeh, Abolfazl; Davaran, Soodabeh

2017-05-01

Among all cancers that affect women, breast cancer has most mortality rate. It is essential to attain more safe and efficient anticancer drugs. Recent advances in medical nanotechnology and biotechnology have caused in novel improvements in breast and other cancer drug delivery. Methotrexate is an anticancer drug that prevents the dihydrofolate reductase enzyme, which inhibits in the formation of DNA, RNA and proteins which have poor water-solubility. For enhancing the solubility and stability of drugs in delivery systems, we used methotrexate-loaded PLGA- beta-cyclodextrin nanoparticles. The PLGA- beta-cyclodextrin nanoparticles were synthesized by a double emulsion method and characterized with FT-IR and SEM. T47D breast cancer cell lines were treated with equal concentrations of methotrexate-loaded PLGA- beta-cyclodextrin nanoparticles and free methotrexate. MTT assay confirmed that methotrexate-loaded PLGA- beta-cyclodextrin nanoparticles enhanced cytotoxicity and drug delivery in T47D breast cancer cells. These results indicate that encapsulated drugs could be effective in controlled drug release for a sustained period would serve the purpose for long-term treatment of many diseases such as breast cancer.

Synthesis and Applications of Multimodal Hybrid Albumin Nanoparticles for Chemotherapeutic Drug Delivery and Photothermal Therapy Platforms

NASA Astrophysics Data System (ADS)

Peralta, Donna V.

Progress has been made in using human serum albumin nanoparticles (HSAPs) as carrier systems for targeted treatment of cancer. Human serum albumin (HSA), the most abundant human blood protein, can form HSAPs via a desolvation and crosslinking method, with the size of the HSAPs having crucial importance for drug loading and in vivo performance. Gold nanoparticles have also gained medicinal attention due to their ability to absorb near-infrared (NIR) light. These relatively non-toxic particles offer combinational therapy via imaging and photothermal therapy (PPTT) capabilities. A desolvation and crosslinking approach was employed to encapsulate gold nanoparticles (AuNPs), hollow gold nanoshells (AuNSs), and gold nanorods (AuNRs), into efficiently sized HSAPs for future tumor heat ablation via PPTT. The AuNR-HSAPs, AuNP-HSAPs and AuNS-HSAPs had average particle diameters of 222 +/- 5, 195 +/- 9 and 156 +/- 15, respectively. We simultaneously encapsulated AuNRs and the anticancer drug paclitaxel (PAC), forming PAC-AuNR-HSAPs with overall average particle size of 299 +/- 6 nm. Loading of paclitaxel into PAC-AuNR-HSAPs reached 3microg PAC/mg HSA. PAC-AuNR-HSAPs experienced photothermal heating of 46 °C after 15 minutes of NIR laser exposure; the temperature necessary to cause severe cellular hyperthermia. There was a burst release of paclitaxel up to 188 ng caused by the irradiation session, followed by a temporal drug release. AuNR-HSAPs were tested for ablation of renal cell carcinoma using NIR irradiation in vitro. Particles created with the same amount of AuNRs, but varying HSA (1, 5 or 20 mg) showed overall particle size diameters 409 +/- 224, 294 +/- 83 and 167 +/- 4 nm, respectively. Increasing HSAPs causes more toxicity under non-irradiated treatment conditions: AuNR-HSAPs with 20 mg versus 5 mg HSA caused cell viability of 64.5% versus 87%, respectively. All AuNR-HSAPs batches experienced photothermal heating above 42 °C. Coumarin-6, was used to visualize the cellular uptake of AuNR-HSAPs via fluorescence microscopy. Finally, camptothecin (CPT) an antineoplastic agent and BACPT (7-butyl-10-aminocamptothecin) were loaded into HSAPs to combat their aqueous insolubility. BACPT-HSAPs loaded up to 5.25 micrograms BACPT/ mg of HSA. CPT encapsulation could not be determined. BACPT-HSAPs and CPT-HSAPs showed cytotoxicity to human sarcoma cells in vitro. Key words: Hybrid Nanoparticles, Photothermal Therapy, Gold Nanomaterials, Drug Delivery, Combinational Cancer Therapies, Materials, Human Serum Albumin, Colloidal Carriers.

Redox and pH Dual-Responsive Polymeric Micelles with Aggregation-Induced Emission Feature for Cellular Imaging and Chemotherapy.

PubMed

Zhuang, Weihua; Xu, Yangyang; Li, Gaocan; Hu, Jun; Ma, Boxuan; Yu, Tao; Su, Xin; Wang, Yunbing

2018-05-21

Intelligent polymeric micelles for antitumor drug delivery and tumor bioimaging have drawn a broad attention because of their reduced systemic toxicity, enhanced efficacy of drugs, and potential application of tumor diagnosis. Herein, we developed a multifunctional polymeric micelle system based on a pH and redox dual-responsive mPEG-P(TPE- co-AEMA) copolymer for stimuli-triggered drug release and aggregation-induced emission (AIE) active imaging. These mPEG-P(TPE- co-AEMA)-based micelles showed excellent biocompatibility and emission property, exhibiting great potential application for cellular imaging. Furthermore, the antitumor drug doxorubicin (DOX) could be encapsulated during self-assembly process with high loading efficiency, and a DOX-loaded micelle system with a size of 68.2 nm and narrow size distribution could be obtained. DOX-loaded micelles demonstrated great tumor suppression ability in vitro, and the dual-responsive triggered intracellular drug release could be further traced. Moreover, DOX-loaded micelles could efficiently accumulate at the tumor site because of enhanced permeability and retention effect and long circulation of micelles. Compared with free DOX, DOX-loaded micelles exhibited better antitumor effect and significantly reduced adverse effects. Given the efficient accumulation targeting to tumor tissue, dual-responsive drug release, and excellent AIE property, this polymeric micelle would be a potential candidate for cancer therapy and diagnosis.

Miconazole Nitrate-loaded Microparticles For Buccal Use: Immediate Drug Release and Antifungal Effect.

PubMed

Cartagena, Andres Felipe; Lyra, Amanda Martinez; Kapuchczinski, Aline Cristina; Urban, Amanda Migliorini; Esmerino, Luis Antonio; Klein, Traudi; Nadal, Jessica Mendes; Farago, Paulo Vitor; Campanha, Nara Hellen

2017-01-01

Miconazole nitrate has been widely employed in treatment of oral mycoses, however your immediate bio-availability and location in the affected area is critical. The aim of this study was to prepare and evaluate Eudragit® L100 and Gantrez MS-955 microparticles containing miconazole nitrate for oral delivery. Microparticles were prepared by spray-drying method to achieve high encapsulation efficiency and increase the drug solubility. The microparticles were formed containing 10% and 20% of drug on polymer Eudragit® L100 (E10 and E20), Gantrez MS-955 (G10 and G20) or their combination (EG10 and EG20). The influence of formulation factors (polymer:drug ratio, type of polymer) on yield percent, encapsulation efficiency, particle size, Fourier-transformed infrared spectroscopy (FTIR), X-ray diffraction, differential scanning calorimetry, in vitro drug release and antifungal activity were investigated. Acceptable yield, micrometer-sized and drug-loading efficiencies higher than 89% were obtained. No change in FTIR assignments was recorded after the microencapsulation procedure. X-ray and differential scanning calorimetry studies revealed amorphous/non-crystalline formulations. Miconazole nitrate-microparticles provided a remarkable increase of dissolution rate of the drug. Miconazole nitrate and G10, G20 and EG20 microparticles fitted to biexponential kinetic model, and E10, E20 and EG10 microparticles, monoexponential kinetic model. The antifungal activity test demonstrated that miconazole nitrate-microparticles possessed the same anti-Candida albicans activity as the pure drug. These results indicate that miconazole nitrate-microparticles are feasible carriers for increased release of miconazole at oral environment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs.

PubMed

Butt, Adeel Masood; Mohd Amin, Mohd Cairul Iqbal; Katas, Haliza

2015-01-01

Doxorubicin (DOX), an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407) and vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate, TPGS) are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA) for folate-mediated receptor targeting to cancer cells. FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue(®) assay. The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX-DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX. FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer activity, inhibition of multidrug resistance, and folate-mediated selective uptake.

Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

PubMed Central

Butt, Adeel Masood; Mohd Amin, Mohd Cairul Iqbal; Katas, Haliza

2015-01-01

Background Doxorubicin (DOX), an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407) and vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate, TPGS) are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA) for folate-mediated receptor targeting to cancer cells. Methods FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue® assay. Results The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX–DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX. Conclusion FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer activity, inhibition of multidrug resistance, and folate-mediated selective uptake. PMID:25709451

Fabrication of doxorubicin nanoparticles by controlled antisolvent precipitation for enhanced intracellular delivery.

PubMed

Tam, Yu Tong; To, Kenneth Kin Wah; Chow, Albert Hee Lum

2016-03-01

Over-expression of ATP-binding cassette transporters is one of the most important mechanisms responsible for multidrug resistance. Here, we aimed to develop a stable polymeric nanoparticle system by flash nanoprecipitation (FNP) for enhanced anticancer drug delivery into drug resistant cancer cells. As an antisolvent precipitation process, FNP works best for highly lipophilic solutes (logP>6). Thus we also aimed to evaluate the applicability of FNP to drugs with relatively low lipophilicity (logP=1-2). To this end, doxorubicin (DOX), an anthracycline anticancer agent and a P-gp substrate with a logP of 1.3, was selected as a model drug for the assessment. DOX was successfully incorporated into the amphiphilic diblock copolymer, polyethylene glycol-b-polylactic acid (PEG-b-PLA), by FNP using a four-stream multi-inlet vortex mixer. Optimization of key processing parameters and co-formulation with the co-stabilizer, polyvinylpyrrolidone, yielded highly stable, roughly spherical DOX-loaded PEG-b-PLA nanoparticles (DOX.NP) with mean particle size below 100nm, drug loading up to 14%, and drug encapsulation efficiency up to 49%. DOX.NP exhibited a pH-dependent drug release profile with higher cumulative release rate at acidic pHs. Surface analysis of DOX.NP by XPS revealed an absence of DOX on the particle surface, indicative of complete drug encapsulation. While there were no significant differences in cytotoxic effect on P-gp over-expressing LCC6/MDR cell line between DOX.NP and free DOX in buffered aqueous media, DOX.NP exhibited a considerably higher cellular uptake and intracellular retention after efflux. The apparent lack of cytotoxicity enhancement with DOX.NP may be attributable to its slow DOX release inside the cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Dual drug loaded chitosan nanoparticles-sugar--coated arsenal against pancreatic cancer.

PubMed

David, Karolyn Infanta; Jaidev, Leela Raghav; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

2015-11-01

Pancreatic cancer is an aggressive form of cancer with poor survival rates. The increased mortality due to pancreatic cancer arises due to many factors such as development of multidrug resistance, presence of cancer stem cells, development of a stromal barrier and a hypoxic environment due to hypo-perfusion. The present study aims to develop a nanocarrier for a combination of drugs that can address these multiple issues. Quercetin and 5-fluorouracil were loaded in chitosan nanoparticles, individually as well as in combination. The nanoparticles were characterized for morphology, size, zeta potential, percentage encapsulation of drugs as well as their release profiles in different media. The dual drug-loaded carrier exhibited good entrapment efficiency (quercetin 95% and 5-fluorouracil 75%) with chitosan: quercetin: 5-fluorouracil in the ratio 3:1:2. The release profiles suggest that 5-fluorouracil preferentially localized in the periphery while quercetin was located towards the core of chitosan nanoparticles. Both drugs exhibited considerable association with the chitosan matrix. The dual drug-loaded carrier system exhibited significant toxicity towards pancreatic cancer cells both in the 2D as well as in the 3D cultures. We believe that the results from these studies can open up interesting options in the treatment of pancreatic cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

Metal coated colloidosomes as carriers for an antibiotic

NASA Astrophysics Data System (ADS)

Sun, Qian; Zhao, Ziyan; Hall, Elizabeth A. H.; Routh, Alexander F.

2018-06-01

Colloidosomes are polymer shell microcapsules. They are stable and easy to prepare and have been used to encapsulate drugs for release at specific areas in the body. Traditional polymer shell capsules cannot totally seal drugs, since they are porous and small molecules diffuse through the polymer shell. In this paper, we report a method for encapsulating an antibiotic kanamycin using gold or silver coated colloidosomes. The colloidosomes are impermeable and can be triggered using ultrasound. To investigate the application of the capsules in a biological system, Escherichia Coli (E.coli) was chosen as a model organism. After triggering, the released antibiotic, as well as the metal shell fragments, kill E.coli. Both the silver and gold shells colloidosomes are toxic to this bacterial system and the gold coated colloidosomes can load a higher concentration of kanamycin.

Monodispersed silk fibroin microdroplets for protein stabilization

NASA Astrophysics Data System (ADS)

Liu, Qiang; Jiang, Nan; Liu, Dewen; Ying, Guoliang; Shi, Qiusheng; Yetisen, Ali K.; Liu, Haifeng; Fan, Yubo

2018-04-01

Low stability of globular protein droplets in emulsion significantly limits their applications in drug encapsulation, long-term storage, and controlled drug release. Here, a microfluidic flow-focusing device was utilized to synthesize horseradish peroxidase (HRP)-loaded silk fibroin microdroplets. The two immiscible streams of microfluidic flow-focusing were regenerated by silk fibroin solution and a mixture of 95 wt. % sunflower oil and 5 wt. % span 80 as the dispersed and continuous phases, respectively. In this study, the water-in-oil silk fibroin microdroplets were homogeneously produced by leveraging the discrete and periodic breakup of microdroplets and regulating the flow rates. Moreover, the result showed that the stability of encapsulated HRP in microdroplets was 25% higher than that of HRP after 6 weeks incubation. Thus, the microfluidic flow-focusing is a promising technique to form monodisperse microdroplets and maximize the stability of protein droplets.

Engineering of budesonide-loaded lipid-polymer hybrid nanoparticles using a quality-by-design approach.

PubMed

Leng, Donglei; Thanki, Kaushik; Fattal, Elias; Foged, Camilla; Yang, Mingshi

2017-08-25

Chronic obstructive pulmonary disease (COPD) is a complex disease, characterized by persistent airflow limitation and chronic inflammation. The purpose of this study was to design lipid-polymer hybrid nanoparticles (LPNs) loaded with the corticosteroid, budesonide, which could potentially be combined with small interfering RNA (siRNA) for COPD management. Here, we prepared LPNs based on the biodegradable polymer poly(dl-lactic-co-glycolic acid) (PLGA) and the cationic lipid dioleyltrimethylammonium propane (DOTAP) using a double emulsion solvent evaporation method. A quality-by-design (QbD) approach was adopted to define the optimal formulation parameters. The quality target product profile (QTPP) of the LPNs was identified based on risk assessment. Two critical formulation parameters (CFPs) were identified, including the theoretical budesonide loading and the theoretical DOTAP loading. The CFPs were linked to critical quality attributes (CQAs), which included the intensity-based hydrodynamic particle diameter (z-average), the polydispersity index (PDI), the zeta-potential, the budesonide encapsulation efficiency, the actual budesonide loading and the DOTAP encapsulation efficiency. A response surface methodology (RSM) was applied for the experimental design to evaluate the influence of the CFPs on the CQAs, and to identify the optimal operation space (OOS). All nanoparticle dispersions displayed monodisperse size distributions (PDI<0.2) with z-averages of approximately 150nm, suggesting that the size is not dependent on the investigated CFPs. In contrast, the zeta-potential was highly dependent on the theoretical DOTAP loading. Upon increased DOTAP loading, the zeta-potential reached a maximal point, after which it remained stable at the maximum value. This suggests that the LPN surface is covered by DOTAP, and that the DOTAP loading is saturable. The actual budesonide loading of the LPNs was mainly dependent on the initial amount of budesonide, and a clear positive effect was observed, which shows that the interaction between drug and PLGA increases when increasing the initial amount of budesonide. The OOS was modeled by applying the QTPP. The OOS had a budesonide encapsulation efficiency higher than 30%, a budesonide loading above 15μg budesonide/mg PLGA, a zeta-potential higher than 35mV and a DOTAP encapsulation efficiency above 50%. This study shows the importance of systematic formulation design for understanding the effect of formulation parameters on the characteristics of LPNs, eventually resulting in the identification of an OOS. Copyright © 2017 Elsevier B.V. All rights reserved.

Microfluidic assembly of a nano-in-micro dual drug delivery platform composed of halloysite nanotubes and a pH-responsive polymer for colon cancer therapy.

PubMed

Li, Wei; Liu, Dongfei; Zhang, Hongbo; Correia, Alexandra; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2017-01-15

Harsh conditions of the gastrointestinal tract hinder the oral delivery of many drugs. Developing oral drug delivery systems based on commercially available materials is becoming more challenging due to the demand for simultaneously delivering physicochemically different drugs for treating complex diseases. A novel architecture, namely nanotube-in-microsphere, was developed as a drug delivery platform by encapsulating halloysite nanotubes (HNTs) in a pH-responsive hydroxypropyl methylcellulose acetate succinate polymer using microfluidics. HNTs were selected as orally acceptable clay mineral and their lumen was enlarged by selective acid etching. Model drugs (atorvastatin and celecoxib) with different physicochemical properties and synergistic effect on colon cancer prevention and inhibition were simultaneously incorporated into the microspheres at a precise ratio, with atorvastatin and celecoxib being loaded in the HNTs and polymer matrix, respectively. The microspheres showed spherical shape, narrow particle size distribution and pH-responsive dissolution behavior. This nanotube/pH-responsive polymer composite protected the loaded drugs from premature release at pH⩽6.5, but allowed their fast release and enhanced the drug permeability, and the inhibition of colon cancer cell proliferation at pH 7.4. Overall, the nano-in-micro drug delivery composite fabricated by microfluidics is a promising and flexible platform for the delivery of multiple drugs for combination therapy. Halloysite nanotubes (HNTs) are attracting increasing attention for drug delivery applications. However, conventional HNTs-based oral drug delivery systems are lack of the capability to precisely control the drug release at a desired site in the gastrointestinal tract. In this study, a nanotube-in-microsphere drug delivery platform is developed by encapsulating HNTs in a pH-responsive polymer using microfluidics. Drugs with different physicochemical properties and synergistic effect on colon cancer therapy were simultaneously incorporated in the microspheres. The prepared microspheres prevented the premature release of the loaded drugs after exposure to the harsh conditions of the gastrointestinal tract, but allowed their simultaneously fast release, and enhanced the drug permeability and the inhibition of colon cancer cell proliferation in response to the colon pH. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Highly versatile SPION encapsulated PLGA nanoparticles as photothermal ablators of cancer cells and as multimodal imaging agents.

PubMed

Sivakumar, Balasubramanian; Aswathy, Ravindran Girija; Romero-Aburto, Rebeca; Mitcham, Trevor; Mitchel, Keith A; Nagaoka, Yutaka; Bouchard, Richard R; Ajayan, Pulickel M; Maekawa, Toru; Sakthikumar, Dasappan Nair

2017-02-28

We have designed versatile polymeric nanoparticles with cancer cell specific targeting capabilities via aptamer conjugation after the successful encapsulation of curcumin and superparamagnetic iron oxide nanoparticles (SPIONs) inside a PLGA nanocapsule. These targeted nanocomposites were selectively taken up by tumor cells, under in vitro conditions, demonstrating the effectiveness of the aptamer targeting mechanism. Moreover, the nanocomposite potentially functioned as efficient multiprobes for optical, magnetic resonance imaging (MRI) and photoacoustic imaging contrast agents in the field of cancer diagnostics. The hyperthermic ability of these nanocomposites was mediated by SPIONs upon NIR-laser irradiation. In vitro cytotoxicity was shown by curcumin-loaded nanoparticles as well as the photothermal ablation of cancer cells mediated by the drug-encapsulated nanocomposite demonstrated the potential therapeutic effect of the nanocomposite. In short, we portray the aptamer-conjugated nanocomposite as a multimodal material capable of serving as a contrast agent for MR, photoacoustic and optical imaging. Furthermore, the nanocomposite functions as a targetable drug nanocarrier and a NIR-laser inducible hyperthermic material that is capable of ablating PANC-1 and MIA PaCa-2 cancer cell lines.

Evaluation of an oral carrier system in rats: bioavailability and gastrointestinal absorption properties of curcumin encapsulated PBCA nanoparticles

NASA Astrophysics Data System (ADS)

Sun, Min; Zhao, Lixia; Guo, Chenyu; Cao, Fengliang; Chen, Huanlei; Zhao, Liyan; Tan, Qi; Zhu, Xiuqing; Zhu, Fanping; Ding, Tingting; Zhai, Yingjie; Zhai, Guangxi

2012-02-01

A new oral delivery system, polybutylcyanoacrylate nanoparticles (PBCNs), was introduced to improve the oral bioavailability of curcumin (CUR), a poorly soluble drug. The formulation was optimized by orthogonal design and the optimal PBCNs loading CUR exhibited a spherical shape under transmission electron microscopy with a range of 40-400 nm. Physicochemical state of CUR in PBCN was investigated by X-ray diffraction and the possible structure changes occurring in CUR after conjugating with polybutylcyanoacrylate were studied with FTIR. The results indicated that CUR in PBCN was in a non-crystalline state and CUR was encapsulated in PBCN without chemical reaction. The oral pharmacokinetic study was conducted in rats and the relative bioavailability of CUR encapsulated PBCNs to the crude CUR was more than 800%. The in situ absorption experiment in rat intestine indicated the absorption was first order with passive diffusion mechanism. The absorption results in various segments of intestine showed that the main absorption sites were ileum and colon. It can be concluded that PBCNs as an oral carrier can significantly improve the oral absorption of a poorly soluble drug.

Elevating bioavailability of cyclosporine a via encapsulation in artificial oil bodies stabilized by caleosin.

PubMed

Chen, Miles C M; Wang, Jui-Ling; Tzen, Jason T C

2005-01-01

To elevate its bioavailability via oral administration, cyclosporine A (CsA), a hydrophobic drug, was either incorporated into olive oil directly or encapsulated in artificial oil bodies (AOBs) constituted with olive oil and phospholipid in the presence or absence of recombinant caleosin purified from Escherichia coli. The bioavailabilities of CsA in these formulations were assessed in Wistar rats in comparison with the commercial formulation, Sandimmun Neoral. Among these tests, CsA-loaded AOBs stabilized by the recombinant caleosin exhibited better bioavailability than the commercial formulation and possessed the highest maximum whole blood concentration (C(max)), 1247.4 +/- 106.8 ng/mL, in the experimental animals 4.3 +/- 0.7 h (t(max)) after oral administration. C(max) and the area under the plasma concentration-time curve (AUC(0-24)) were individually increased by 50.8% and 71.3% in the rats fed with caleosin-stabilized AOBs when compared with those fed with the reference Sandimmun Neoral. The results suggest that constitution of AOBs stabilized by caleosin may be a suitable technique to encapsulate hydrophobic drugs for oral administration.

Systemic study of solvent-assisted active loading of gambogic acid into liposomes and its formulation optimization for improved delivery.

PubMed

Tang, Wei-Lun; Tang, Wei-Hsin; Szeitz, Andras; Kulkarni, Jayesh; Cullis, Pieter; Li, Shyh-Dar

2018-06-01

The solvent-assisted active loading technology (SALT) was developed for encapsulating a water insoluble weak base into the liposomal core in the presence of 5% DMSO. In this study, we further examined the effect of various water miscible solvents in promoting active loading of other types of drugs into liposomes. To achieve complete drug loading, the amount of solvent required must result in complete drug solubilization and membrane permeability enhancement, but must be below the threshold that induces liposomal aggregation or causes bilayer disruption. We then used the SALT to load gambogic acid (GA, an insoluble model drug that shows promising anticancer effect) into liposomes, and optimized the loading gradient and lipid composition to prepare a stable formulation (Lipo-GA) that displayed >95% drug retention after incubation with serum for 3 days. Lipo-GA contained a high drug-to-lipid ratio of 1/5 (w/w) with a mean particle size of ∼75 nm. It also displayed a prolonged circulation half-life (1.5 h vs. 18.6 h) and enhanced antitumor activity in two syngeneic mice models compared to free GA. Particularly, complete tumor regression was observed in the EMT6 tumor model for 14 d with significant inhibition of multiple oncogenes including HIF-1α, VEGF-A, STAT3, BCL-2, and NF-κB. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Impact of Bubbles on Measurement of Drug Release from Echogenic Liposomes

PubMed Central

Kopechek, Jonathan A.; Haworth, Kevin J.; Radhakrishnan, Kirthi; Huang, Shaoling; Klegerman, Melvin E.; McPherson, David D.; Holland, Christy K.

2013-01-01

Echogenic liposomes (ELIP) encapsulate gas bubbles and drugs within lipid vesicles, but the mechanisms of ultrasound-mediated drug release from ELIP are not well understood. The effect of cavitation activity on drug release from ELIP was investigated in flowing solutions using two fluorescent molecules: a lipophilic drug (rosiglitazone) and a hydrophilic drug substitute (calcein). ELIP samples were exposed to pulsed Doppler ultrasound from a clinical diagnostic ultrasound scanner at pressures above and below the inertial and stable cavitation thresholds. Control samples were exposed to a surfactant, Triton X-100 (positive control), or to flow alone (negative control). Fluorescence techniques were used to detect release. Encapsulated microbubbles reduced the measured fluorescence intensity and this effect should be considered when assessing drug release from ELIP. The origin of this effect is not specific to ELIP. Release of rosiglitazone or calcein compared to the negative control was only observed with detergent treatment, but not with ultrasound exposure, despite the presence of stable and inertial cavitation activity. Release of rosiglitazone or calcein from ELIP exposed to diagnostic ultrasound was not observed, even in the presence of cavitation activity. Ultrasound-mediated drug delivery strategies with ELIP will thus rely on passage of the drug-loaded liposomes to target tissues. PMID:23357288

Protein-Containing Multilayer Capsules by Templating on Mesoporous CaCO3 Particles: POST- and PRE-Loading Approaches.

PubMed

Balabushevich, Nadezhda G; Lopez de Guerenu, Anna V; Feoktistova, Natalia A; Skirtach, Andre G; Volodkin, Dmitry

2016-01-01

Encapsulation of model proteins (catalase, insulin, aprotinin) into multilayer dextran sulphate/protamin capsules by templating on CaCO3 microparticles is investigated employing: (i) PRE-loading into CaCO3 particles by adsorption or co-synthesis and (ii) POST-loading into performed capsules. Protein encapsulation is governed by both its size and electrostatic interactions with the carbonate microparticles and multilayer shell. PRE-loading enables improved encapsulation compared to POST-loading (catalase content in capsules 630 and 70 mg · g(-1)). Bioactivity of encapsulated protein is not affected by interaction with multilayers but may be reduced at slightly alkaline pH due to CaCO3 hydrolysis. This study might help to successfully encapsulate fragile bio-macromolecules into multilayer capsules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and characterization of folate decorated albumin bio-conjugate nanoparticles loaded with a synthetic curcumin difluorinated analogue.

PubMed

Gawde, Kaustubh A; Kesharwani, Prashant; Sau, Samaresh; Sarkar, Fazlul H; Padhye, Subhash; Kashaw, Sushil K; Iyer, Arun K

2017-06-15

Albumin-bound paclitaxel colloidal nanoparticle (Abraxane®) is an FDA approved anticancer formulation available in the market. It is a suspension which is currently used therapeutically for treating cancers of the breast, lung, and pancreas among others. CDF is a novel new and potent synthetic curcumin analogue that is widely used for breast and ovarian cancer. The aim of this study was to use biocompatible albumin as well as folate decorated albumin to formulate colloidal nanoparticles encapsulating curcumin difluorinated (CDF). CDF has demonstrated a 16-fold improvement in stability and remarkable anticancer potency compared to its natural derivative, curcumin. CDF showed marked inhibition of cancer cell growth through down-regulation of multiple miRNAs, up-regulation of phosphatase and tensin homolog (PTEN), and attenuation of histone methyl transferase EZH2. However, CDF is highly hydrophobic and photodegradable with sparing aqueous solubility. In this study, we have formulated albumin nanoparticle using a modified desolvation method, which yielded high CDF loading in a nanoformulation. The physicochemical properties of CDF loaded albumin and folate-decorated albumin nanosuspensions were assessed for particle size, morphology, zeta potential, drug encapsulation efficiency/loading, solubility and drug release. Importantly, the folate ligand decorated albumin nanoparticles were formulated in principle to passively and actively target folate-overexpressing-cancers. In this study, the synthesis and optimization of BSA and folate decorated BSA conjugated CDF nanoparticles are assessed in detail that will be useful for its future clinical translation. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanical properties of single electrospun drug-encapsulated nanofibres

PubMed Central

Chew, Sing Yian; Hufnagel, Todd C; Lim, Chwee Teck; Leong, Kam W

2008-01-01

The mechanical and structural properties of a surface play an important role in determining the morphology of attached cells, and ultimately their cellular functions. As such, mechanical and structural integrity are important design parameters for a tissue scaffold. Electrospun fibrous meshes are widely used in tissue engineering. When in contact with electrospun scaffolds, cells see the individual micro- or nanofibres as their immediate microenvironment. In this study, tensile testing of single electrospun nanofibres composed of poly(ε-caprolactone) (PCL), and its copolymer, poly(caprolactone-co-ethyl ethylene phosphate) (PCLEEP), revealed a size effect in the Young's modulus, E, and tensile strength, σT. Both strength and stiffness increase as the fibre diameter decreases from bulk (∼5 μm) into the nanometre region (200–300 nm). In particular, E and σT of individual PCL nanofibres were at least two-fold and an order of magnitude higher than that of PCL film, respectively. PCL films were observed to have more pronounced crystallographic texture than the nanofibres; however no difference in crystalline fraction, perfection, or texture was detected among the various fibres. When drugs were encapsulated into single PCLEEP fibres, mechanical properties were enhanced with 1–20 wt% of loaded retinoic acid, but weakened by 10–20 wt% of encapsulated bovine serum albumin. This understanding of the effect of size and drug and protein encapsulation on the mechanical properties of electrospun fibres may help in the optimization of tissue scaffold design that combines biochemical and biomechanical cues for tissue regeneration. PMID:19079553

Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

PubMed

García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

2015-03-30

Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis and characterization of amphiphilic block polymer poly(ethylene glycol)-poly(propylene carbonate)-poly(ethylene glycol) for drug delivery.

PubMed

Li, Hongchun; Niu, Yongsheng

2018-08-01

A novel amphiphilic block polymer poly(ethylene glycol)-poly(propylene carbonate)-poly(ethylene glycol) (PEG-PPC-PEG) was synthesized via the dicyclohexylcarbodiimide condensation reaction of double PEG-bis-amine and HOOC-PPC-COOH. The obtained copolymer was characterized by NMR to determine its structure. Using the PEG-PPC-PEG as the carrier and using doxorubicin (DOX) as a model drug, DOX-loaded nanoparticles with core shell structure were synthesized by self-assembly in water. The nanoparticles properties such as particle size, drug loading, encapsulation efficiency (EE) and drug release behavior were investigated as a function of the hydrophobic block length of PPC segments and compared with each other. The results showed that the EE was up to 88.8%. Nanoparticles were found to have a certain effect on the controlled release of DOX. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhanced tumor targeting of cRGD peptide-conjugated albumin nanoparticles in the BxPC-3 cell line.

PubMed

Yu, Xinzhe; Song, Yunlong; Di, Yang; He, Hang; Fu, Deliang; Jin, Chen

2016-08-12

The emerging albumin nanoparticle brings new hope for the delivery of antitumor drugs. However, a lack of robust tumor targeting greatly limits its application. In this paper, cyclic arginine-glycine-aspartic-conjugated, gemcitabine-loaded human serum albumin nanoparticles (cRGD-Gem-HSA-NPs) were successfully prepared, characterized, and tested in vitro in the BxPC-3 cell line. Initially, 4-N-myristoyl-gemcitabine (Gem-C14) was formed by conjugating myristoyl to the 4-amino group of gemcitabine. Then, cRGD-HSA was synthesized using sulfosuccinimidyl-(4-N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC) cross-linkers. Finally, cRGD-Gem-HSA-NPs were formulated based on the nanoparticle albumin-bound (nab) technology. The resulting NPs were characterized for particle size, zeta potential, morphology, encapsulation efficiency, and drug loading efficiency. In vitro cellular uptake and inhibition studies were conducted to compare Gem-HSA-NPs and cRGD-Gem-HSA-NPs in a human pancreatic cancer cell line (BxPC-3). The cRGD-Gem-HSA-NPs exhibited an average particle size of 160 ± 23 nm. The encapsulation rate and drug loading rate were approximately 83 ± 5.6% and 11 ± 4.2%, respectively. In vitro, the cRGD-anchored NPs exhibited a significantly greater affinity for the BxPC-3 cells compared to non-targeted NPs and free drug. The cRGD-Gem-HSA-NPs also showed the strongest inhibitory effect in the BxPC-3 cells among all the analyzed groups. The improved efficacy of cRGD-Gem-HSA-NPs in the BxPC-3 cell line warrants further in vivo investigations.

Optimizing indomethacin-loaded chitosan nanoparticle size, encapsulation, and release using Box-Behnken experimental design.

PubMed

Abul Kalam, Mohd; Khan, Abdul Arif; Khan, Shahanavaj; Almalik, Abdulaziz; Alshamsan, Aws

2016-06-01

Indomethacin chitosan nanoparticles (NPs) were developed by ionotropic gelation and optimized by concentrations of chitosan and tripolyphosphate (TPP) and stirring time by 3-factor 3-level Box-Behnken experimental design. Optimal concentration of chitosan (A) and TPP (B) were found 0.6mg/mL and 0.4mg/mL with 120min stirring time (C), with applied constraints of minimizing particle size (R1) and maximizing encapsulation efficiency (R2) and drug release (R3). Based on obtained 3D response surface plots, factors A, B and C were found to give synergistic effect on R1, while factor A has a negative impact on R2 and R3. Interaction of AB was negative on R1 and R2 but positive on R3. The factor AC was having synergistic effect on R1 and on R3, while the same combination had a negative effect on R2. The interaction BC was positive on the all responses. NPs were found in the size range of 321-675nm with zeta potentials (+25 to +32mV) after 6 months storage. Encapsulation, drug release, and content were in the range of 56-79%, 48-73% and 98-99%, respectively. In vitro drug release data were fitted in different kinetic models and pattern of drug release followed Higuchi-matrix type. Copyright © 2016 Elsevier B.V. All rights reserved.

Discovery and in vivo evaluation of novel RGD-modified lipid-polymer hybrid nanoparticles for targeted drug delivery.

PubMed

Zhao, Yinbo; Lin, Dayong; Wu, Fengbo; Guo, Li; He, Gu; Ouyang, Liang; Song, Xiangrong; Huang, Wei; Li, Xiang

2014-09-29

In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs) modified by Arg-Gly-Asp(RGD) peptide, loaded with curcumin (Cur), were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD-lpNPs) could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid))-mPEG (methoxyl poly(ethylene- glycol)), RGD-polyethylene glycol (PEG)-cholesterol (Chol) copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD-lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD-lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD-lpNPs was increased for human umbilical vein endothelial cells (HUVEC). Furthermore, Cur loaded RGD-lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD-lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD-lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD-lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy.

Microfluidics and BIO-encapsulation for drug- and cell-therapy

NASA Astrophysics Data System (ADS)

Aloisi, A.; Toma, C. C.; Di Corato, R.; Rinaldi, R.

2017-08-01

We present the construction and the application of biocompatible micro- and nano-structures that can be administered systemically and transport in a targeted and effective way drugs, small molecules, stem cells or immune system cells. These polymeric nano-systems represent a primary goal for the treatment of a wide family of neurological/systemic disorders, as well as tumors and/or acute injuries. As natural, biocompatible, biodegradable and non-immunogenic building blocks, alginate and chitosan are been currently exploited. Ionotropic pre-gelation of the alginate core, followed by chitosan polyelectrolyte complexation, allows to encapsulate selected active molecules by means of physical entrapment and electrostatic interactions within sub-micron sized hydrogel vesicles. Here we present a microfluidicassisted assembly method of nano- and micro-vesicles -under sterile, closed environment and gas exchange adjustable conditions, which is a critical issue, when the cargo to be uploaded is very sensitive. Polymer/polymer and polymer/drug mass ratio relationship are crucial in order to attain the optimum in terms of shuttle size and cargo concentration. By modulating polymer reticulation conditions, it become possible to control drug loading efficiency as well as drug delivery dynamics. Recent results on the application of these vesicles for the encapsulation and delivery of Inhibin-A and Decorin, proteins involved in acute kidney injury (AKI), for Renal tubular cell regeneration will be presented. Finally, the impact of these polysaccharide sub-micron vesicles on Human Immune cells and the metabolic and functional activity of cells embedded in the assembled vesicles will be presented and discussed.

Vaults Engineered for Hydrophobic Drug Delivery

PubMed Central

Buehler, Daniel C.; Toso, Daniel B.; Kickhoefer, Valerie A.; Zhou, Z. Hong

2013-01-01

The vault nanoparticle is one of the largest known ribonucleoprotein complexes in the sub-100 nm range. Highly conserved and almost ubiquitously expressed in eukaryotes, vaults form a large nanocapsule with a barrel-shaped morphology surrounding a large hollow interior. These properties make vaults an ideal candidate for development into a drug delivery vehicle. In this study, we report the first example of using vaults towards this goal. We engineered recombinant vaults to encapsulate the highly insoluble and toxic hydrophobic compound All-trans Retinoic Acid (ATRA) using a vault binding lipoprotein complex that forms a lipid bilayer nanodisk. These recombinant vaults offer protection to the encapsulated ATRA from external elements. Furthermore, a cryo-electron tomography (cryo-ET) reconstruction shows the vault binding lipoprotein complex sequestered within the vault lumen. Finally, these ATRA loaded vaults have enhanced cytotoxicity against the hepatocellular carcinoma cell line HepG2. The ability to package therapeutic compounds into the vault is an important achievement toward their development into a viable and versatile platform for drug delivery. PMID:21506266

Carrier-inside-carrier: polyelectrolyte microcapsules as reservoir for drug-loaded liposomes.

PubMed

Maniti, Ofelia; Rebaud, Samuel; Sarkis, Joe; Jia, Yi; Zhao, Jie; Marcillat, Olivier; Granjon, Thierry; Blum, Loïc; Li, Junbai; Girard-Egrot, Agnès

2015-01-01

Conventional liposomes have a short life-time in blood, unless they are protected by a polymer envelope, most often polyethylene glycol. However, these stabilizing polymers frequently interfere with cellular uptake, impede liposome-membrane fusion and inhibit escape of liposome content from endosomes. To overcome such drawbacks, polymer-based systems as carriers for liposomes are currently developed. Conforming to this approach, we propose a new and convenient method for embedding small size liposomes, 30-100 nm, inside porous calcium carbonate microparticles. These microparticles served as templates for deposition of various polyelectrolytes to form a protective shell. The carbonate particles were then dissolved to yield hollow polyelectrolyte microcapsules. The main advantage of using this method for liposome encapsulation is that carbonate particles can serve as a sacrificial template for deposition of virtually any polyelectrolyte. By carefully choosing the shell composition, bioavailability of the liposomes and of the encapsulated drug can be modulated to respond to biological requirements and to improve drug delivery to the cytoplasm and avoid endosomal escape.

PLGA/liposome hybrid nanoparticles for short-chain ceramide delivery

PubMed Central

Zou, Peng; Stern, Stephan T.; Sun, Duxin

2014-01-01

Purpose Rapid premature release of lipophilic drugs from liposomal lipid bilayer to plasma proteins and biological membranes is a challenge for targeted drug delivery. The purpose of this study is to reduce premature release of lipophilic short-chain ceramides by encapsulating ceramides into liposomal aqueous interior with the aid of poly( lactic-coglycolicacid) (PLGA). Methods BODIPY FL labeled ceramide (FL-ceramide) and BODIPY-TR labeled ceramide (TR-ceramide) were encapsulated into carboxy-terminated PLGA nanoparticles. The negatively charged PLGA nanoparticles were then encapsulated into cationic liposomes to obtain PLGA/liposome hybrids. As a control, FL-ceramide and/or TR ceramide co-loaded liposomes without PLGA were prepared. The release of ceramides from PLGA/liposome hybrids and liposomes in rat plasma, cultured MDA-MB-231 cells, and rat blood circulation was compared using fluorescence resonance energy transfer (FRET) between FL-ceramide (donor) and TR-ceramide (acceptor). Results FRET analysis showed that FL-ceramide and TR-ceramide in liposomal lipid bilayer were rapidly released during incubation with rat plasma. In contrast, the FL-ceramide and TR-ceramide in PLGA/liposome hybrids showed extended release. FRET images of cells revealed that ceramides in liposomal bilayer were rapidly transferred to cell membranes. In contrast, ceramides in PLGA/liposome hybrids were internalized into cells with nanoparticles simultaneously. Upon intravenous administration to rats, ceramides encapsulated in liposomal bilayer were completely released in 2 minutes. In contrast, ceramides encapsulated in the PLGA core were retained in PLGA/liposome hybrids for 4 hours. Conclusions The PLGA/liposome hybrid nanoparticles reduced in vitro and in vivo premature release of ceramides and offer a viable platform for targeted delivery of lipophilic drugs. PMID:24065591

A novel local anesthetic system: transcriptional transactivator peptide-decorated nanocarriers for skin delivery of ropivacaine.

PubMed

Chen, Chuanyu; You, Peijun

2017-01-01

Barrier properties of the skin and physicochemical properties of drugs are the main factors for the delivery of local anesthetic molecules. The present work evaluates the anesthetic efficacy of drug-loaded nanocarrier (NC) systems for the delivery of local anesthetic drug, ropivacaine (RVC). In this study, transcriptional transactivator peptide (TAT)-decorated RVC-loaded NCs (TAT-RVC/NCs) were successfully fabricated. Physicochemical properties of NCs were determined in terms of particle size, zeta potential, drug encapsulation efficiency, drug-loading capacity, stability, and in vitro drug release. The skin permeation of NCs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and in vivo anesthetic effect was evaluated in mice. The results showed that TAT-RVC/NCs have a mean diameter of 133.2 nm and high drug-loading capacity of 81.7%. From the in vitro skin permeation results, it was observed that transdermal flux of TAT-RVC/NCs was higher than that of RVC-loaded NCs (RVC/NCs) and RVC injection. The evaluation of in vivo anesthetic effect illustrated that TAT-RVC/NCs can enhance the transdermal delivery of RVC by reducing the pain threshold in mice. These results indicate that TAT-decorated NCs systems are useful for overcoming the barrier function of the skin, decreasing the dosage of RVC and enhancing the anesthetic effect. Therefore, TAT-decorated NCs can be used as an effective transdermal delivery system for local anesthesia.

Optimization of diclofenac sodium profile from halloysite nanotubules.

PubMed

Krejčová, Kateřina; Deasy, Patrick B; Rabišková, Miloslava

2013-04-01

Halloysite, aluminosilicate clay with the particle shape of multilayered hollow nanotubes, used in various non-medical applications, e.g. in ceramic industry, was discovered for pharmaceutical purposes in recent years. Several drugs of hydrophilic and lipophilic nature have been successfully encapsulated into halloysite tubules in order to modify their dissolution profile. The main goal of this experiment was to optimize the dissolution profile of diclofenac sodium - a drug with problematic solubility - from halloysite tubules using various polymers. Loading of the drug together with povidone or Eudragit® RS did not lead to drug burst effect reduction and its slower dissolution. In the case of povidone, drug improved wettability and solubilization rather than viscosity increasing expectations were observed. Eudragit® RS formed a solid dispersion with diclofenac sodium and thus the solvent/drug solution penetration through the polymer and not the drug solubility was the dissolution rate limiting factor. Reduction of the burst effect and further prolongation of drug release was achieved by coating the drug-loaded halloysite with chitosan. This formulation exhibited a diffusion-controlled prolonged release following Higuchi kinetic model.

Effects of Particle Hydrophobicity, Surface Charge, Media pH Value and Complexation with Human Serum Albumin on Drug Release Behavior of Mitoxantrone-Loaded Pullulan Nanoparticles

PubMed Central

Tao, Xiaojun; Jin, Shu; Wu, Dehong; Ling, Kai; Yuan, Liming; Lin, Pingfa; Xie, Yongchao; Yang, Xiaoping

2015-01-01

We prepared two types of cholesterol hydrophobically modified pullulan nanoparticles (CHP) and carboxyethyl hydrophobically modified pullulan nanoparticles (CHCP) substituted with various degrees of cholesterol, including 3.11, 6.03, 6.91 and 3.46 per polymer, and named CHP−3.11, CHP−6.03, CHP−6.91 and CHCP−3.46. Dynamic laser light scattering (DLS) showed that the pullulan nanoparticles were 80–120 nm depending on the degree of cholesterol substitution. The mean size of CHCP nanoparticles was about 160 nm, with zeta potential −19.9 mV, larger than CHP because of the carboxyethyl group. A greater degree of cholesterol substitution conferred greater nanoparticle hydrophobicity. Drug-loading efficiency depended on nanoparticle hydrophobicity, that is, nanoparticles with the greatest degree of cholesterol substitution (6.91) showed the most drug encapsulation efficiency (90.2%). The amount of drug loading increased and that of drug release decreased with enhanced nanoparticle hydrophobicity. Nanoparticle surface-negative charge disturbed the amount of drug loading and drug release, for an opposite effect relative to nanoparticle hydrophobicity. The drug release in pullulan nanoparticles was higher pH 4.0 than pH 6.8 media. However, the changed drug release amount was not larger for negative-surface nanoparticles than CHP nanoparticles in the acid release media. Drug release of pullulan nanoparticles was further slowed with human serum albumin complexation and was little affected by nanoparticle hydrophobicity and surface negative charge. PMID:28344259

Controlled release of bioactive PDGF-AA from a hydrogel/nanoparticle composite.

PubMed

Elliott Donaghue, Irja; Shoichet, Molly S

2015-10-01

Polymer excipients, such as low molar mass poly(ethylene glycol) (PEG), have shown contradictory effects on protein stability when co-encapsulated in polymeric nanoparticles. To gain further insight into these effects, platelet-derived growth factor (PDGF-AA) was encapsulated in polymeric nanoparticles with vs. without PEG. PDGF-AA is a particularly compelling protein, as it has been demonstrated to promote cell survival and induce the oligodendrocyte differentiation of neural stem/progenitor cells (NSPCs) both in vitro and in vivo. Here we show, for the first time, the controlled release of bioactive PDGF-AA from an injectable nanoparticle/hydrogel drug delivery system (DDS). PDGF-AA was encapsulated, with high efficiency, in poly(lactide-co-glycolide) nanoparticles, and its release from the drug delivery system was followed over 21 d. Interestingly, the co-encapsulation of low molecular weight poly(ethylene glycol) increased the PDGF-AA loading but, unexpectedly, accelerated the aggregation of PDGF-AA, resulting in reduced activity and detection by enzyme-linked immunosorbent assay (ELISA). In the absence of PEG, released PDGF-AA remained bioactive as demonstrated with NSPC oligodendrocyte differentiation, similar to positive controls, and significantly different from untreated controls. This work presents a novel delivery method for differentiation factors, such as PDGF-AA, and provides insights into the contradictory effects reported in the literature of excipients, such as PEG, on the loading and release of proteins from polymeric nanoparticles. Previously, the polymer poly(ethylene glycol) (PEG) has been used in many biomaterials applications, from surface coatings to the encapsulation of proteins. In this work, we demonstrate that, unexpectedly, low molecular weight PEG has a deleterious effect on the release of the encapsulated protein platelet-derived growth factor AA (PDGF-AA). We also demonstrate release of bioactive PDGF-AA (in the absence of PEG). Specifically, we demonstrate the differentiation of neural stem and progenitor cells to oligodendrocytes, similar to what is observed with the addition of fresh PDGFAA. A differentiated oligodendrocyte population is a key strategy in central nervous system regeneration. This work is the first demonstration of controlled PDGF-AA release, and also brings new insights to the broader field of protein encapsulation. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Formulation and transport properties of tenofovir loaded liposomes through Caco-2 cell model.

PubMed

Zidan, Ahmed S; Spinks, Crystal B; Habib, Muhammad J; Khan, Mansoor A

2013-12-01

The aim was to investigate the potential of proliposomes to improve the permeability of tenofovir, anti-HIV, for oral delivery. Tenofovir was incorporated into phosphatidylcholine proliposomes and their absorption was determined in Caco-2 cell cultures grown on Transwell inserts using aqueous drug solutions as reference. Five batches of proliposomes were prepared with different stearylamine levels and characterized in terms of vesicular morphology, drug encapsulation efficiency (EEF), drug leakage, vesicular sizing and surface charges. Cytotoxicity of the reconstituted liposomes was evaluated by the MTT assay. The obtained results showed that increasing the incorporated percentage of stearylamine led to an increase in drug encapsulation, a slower drug leakage and larger liposomes formed. Compared to the drug solutions at corresponding concentrations, the proposed formulations showed a positive relationship (R²= 0.9756) for the influence of increasing the stearylamine percentage on reduction of mitochondrial activity. Regarding the drug permeability, enhancements of apparent permeability by 16.5- and 5.2-folds were observed for proliposomes formulations with 5% and 15% stearylamine, respectively. A good correlation was observed between the Caco-2 and dialysis models that might indicate passive diffusion as well as paracellular transport as suggested mechanisms for drug absorption. Cationic proliposomes offered a potential formulation to improve the permeation of tenofovir.

Using DNA nanotechnology to produce a drug delivery system

NASA Astrophysics Data System (ADS)

Huyen La, Thi; Thu Thuy Nguyen, Thi; Phuc Pham, Van; Huyen Nguyen, Thi Minh; Huan Le, Quang

2013-03-01

Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October-2 November, 2012, Ha Long, Vietnam.

Preparation of a novel breviscapine-loaded halloysite nanotubes complex for controlled release of breviscapine

NASA Astrophysics Data System (ADS)

Gao, Min; Lu, Liqian; Wang, Xiaoyue; Lin, Houke; Zhou, Qingsong

2017-11-01

For sustain the release rate and prolong half-life of breviscapine in vivo, the breviscapine-loaded halloysite nanotubes complex was prepared. The breviscapine was encapsulated into halloysite nanotubes (HNTs) using a vacuum process. The complex were investigated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD) and fourier transform infrared spectroscopy(FT-IR). The formation of breviscapine-loaded HNTs complex was proved by the test results of SEM, DSC, TEM and IR analysise. The results confirmed that breviscapine was successfully loaded in the halloysite nanotubes. Additionally, the in vitro drug release of breviscapine from breviscapine-loaded HNTs complex was investigated, the result indicated this complex has apparent sustained-release effect.

Self-folding polymeric containers for encapsulation and delivery of drugs.

PubMed

Fernandes, Rohan; Gracias, David H

2012-11-01

Self-folding broadly refers to self-assembly processes wherein thin films or interconnected planar templates curve, roll-up or fold into three dimensional (3D) structures such as cylindrical tubes, spirals, corrugated sheets or polyhedra. The process has been demonstrated with metallic, semiconducting and polymeric films and has been used to curve tubes with diameters as small as 2nm and fold polyhedra as small as 100nm, with a surface patterning resolution of 15nm. Self-folding methods are important for drug delivery applications since they provide a means to realize 3D, biocompatible, all-polymeric containers with well-tailored composition, size, shape, wall thickness, porosity, surface patterns and chemistry. Self-folding is also a highly parallel process, and it is possible to encapsulate or self-load therapeutic cargo during assembly. A variety of therapeutic cargos such as small molecules, peptides, proteins, bacteria, fungi and mammalian cells have been encapsulated in self-folded polymeric containers. In this review, we focus on self-folding of all-polymeric containers. We discuss the mechanistic aspects of self-folding of polymeric containers driven by differential stresses or surface tension forces, the applications of self-folding polymers in drug delivery and we outline future challenges. Copyright © 2012 Elsevier B.V. All rights reserved.

Fabrication of functional hollow microspheres constructed from MOF shells: Promising drug delivery systems with high loading capacity and targeted transport

PubMed Central

Gao, Xuechuan; Hai, Xiao; Baigude, Huricha; Guan, Weihua; Liu, Zhiliang

2016-01-01

An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release. PMID:27876876

Drug packaging and delivery using perfluorocarbon nanoparticles for targeted inhibition of vascular smooth muscle cells

PubMed Central

Zhou, Zhao-xiong; Zhang, Bai-gen; Zhang, Hao; Huang, Xiao-zhong; Hu, Ya-li; Sun, Li; Wang, Xiao-min; Zhang, Ji-wei

2009-01-01

Aim: To investigate the in vitro release profile of drugs encapsulated within perfluorocarbon (PFC) nanoparticles (NPs) and their ability to inhibit the activity of vascular smooth muscle cells (SMCs). Methods: Dexamethasone phosphate (DxP) or dexamethasone acetate (DxA) was encapsulated into PFC nanoparticles using a high-pressure homogenous method. The morphology and size of the NPs were examined using scanning electron microscopy (SEM) and a laser particle size analyzer. Drug loading and in vitro release were assessed by high-performance liquid chromatography (HPLC). The impact of NP capsules on SMC proliferation, migration and apoptosis in vitro was assessed using cell counting kit-8, transwell cell migration and flow cytometry assays. Results: The sizes of DxP-NPs and DxA-NPs were 224±6 nm and 236±9 nm, respectively. The encapsulation efficiency (EE) of DxP-NPs was 66.4%±1.0%, with an initial release rate of 77.2%, whereas the EE of DxA-NPs was 95.3%±1.3%, with an initial release rate of 23.6%. Both of the NP-coated drugs could be released over 7 d. Human umbilical artery SMCs were harvested and cultured for four to six passages. Compared to free DxP, SMCs treated with tissue factor (TF)-directed DxP-NPs showed significant differences in the inhibition of proliferation, migration and apoptosis (P<0.05). Conclusion: The results collectively suggest that PFC nanoparticles will be beneficial for targeted drug delivery because of the sustained drug release and effective inhibition of SMC proliferation and migration. PMID:19890365

One-pot green synthesis of doxorubicin loaded-silica nanoparticles for in vivo cancer therapy.

PubMed

Jiang, Shan; Hua, Li; Guo, Zilong; Sun, Lin

2018-09-01

The present work reveals a new and simple one-pot green method to load doxorubicin (DOX) drugs in silica nanoparticles for efficient in vivo cancer therapy. The synthesis of DOX loaded silica nanoparticles (SiNPs/DOX) is based on the efficient encapsulation of DOX in surfactant Tween 80 micelles which act as a template for the formation of silica nanoparticles. The release profile, cellular uptake behavior, cytotoxicity and antitumor effect of SiNPs/DOX nanoparticles were investigated and compared to free DOX. The silica nanoparticles improved the cellular drug delivery efficiency and exhibited high cytotoxicity, successfully achieving the inhibition of tumor growth. Notably, the tumor size and weight of SiNPs/DOX group was 2-fold and 1.7-fold smaller than that of free DOX group, and 4-fold and 2-fold smaller than that of PBS group. The one-pot green synthesis system may have the potential to be developed as a promising drug delivery system. Copyright © 2018 Elsevier B.V. All rights reserved.

Liposome-encapsulated actinomycin for cancer chemotherapy

DOEpatents

Rahman, Yueh-Erh; Cerny, Elizabeth A.

1976-01-01

An improved method is provided for chemotherapy of malignant tumors by injection of antitumor drugs. The antitumor drug is encapsulated within liposomes and the liposomes containing the encapsulated drug are injected into the body. The encapsulated drug penetrates into the tumor cells where the drug is slowly released and induces degeneration and death of the tumor cells, while any toxicity to the host body is reduced. Liposome encapsulation of actinomycin D has been found to be particularly effective in treating cancerous abdominal tumors, while drastically reducing the toxicity of actinomycin D to the host.

Preparation, characterization and evaluation of ranitidine hydrochloride-loaded mucoadhesive microspheres.

PubMed

Dhankar, Vandana; Garg, Garima; Dhamija, Koushal; Awasthi, Rajendra

2014-01-01

Mucoadhesion enables localization of drugs to a defined region of the gastrointestinal tract through attractive interactions between polymers composing the drug delivery devices and the mucin layer of the intestinal epithelium. Thus, this approach can be used for enhancement of the oral bioavailability of the drug. The current communication deals with the development of ranitidine hydrochloride-loaded chitosan-based mucoadhesive microspheres. Microspheres were prepared by water-in-oil emulsion technique, using glutaraldehyde as a cross-linking agent. The effect of independent variables like stirring speed and polymer-to-drug ratio on dependent variables, i.e. percentage mucoadhesion, percentage drug loading, particle size and swelling index, was examined using a 3(2); factorial design. The microspheres were discrete, spherical, free-flowing and also showed high percentage drug entrapment efficiency (43-70%). An in vitro mucoadhesion test showed that the microspheres adhered strongly to the mucous layer for an extended period of time. The RC 4 batch exhibited a high percentage of drug encapsulation (70%) and mucoadhesion (75%). The drug release was sustained for more than 12 h. The drug release kinetics were found to follow Peppas' kinetics for all the formulations and the drug release was diffusion controlled. The preliminary results of this study suggest that the developed microspheres containing ranitidine hydrochloride could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.

[Preparation of ibuprofen/EC-PVP sustained-release composite particles by supercritical CO2 anti-solvent technology].

PubMed

Cai, Jin-Yuan; Huang, De-Chun; Wang, Zhi-Xiang; Dang, Bei-Lei; Wang, Qiu-Ling; Su, Xin-Guang

2012-06-01

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

A modified spontaneous emulsification solvent diffusion method for the preparation of curcumin-loaded PLGA nanoparticles with enhanced in vitro anti-tumor activity

NASA Astrophysics Data System (ADS)

Chen, Cen; Yang, Wei; Wang, Dan-Tong; Chen, Chao-Long; Zhuang, Qing-Ye; Kong, Xiang-Dong

2014-12-01

To improve the anti-tumor activity of hydrophobic drug curcumin, we prepared curcumin-loaded PLGA nanoparticles (PLGA-Cur NPs) through a modified spontaneous emulsification solvent diffusion (modified-SESD) method. The influence of main preparation parameters was investigated, such as the volume ratio of binary organic solvents and the concentration of surfactant. Results indicated that the synthesized regular spherical PLGA NPs with the average diameter of 189.7 nm exhibited relatively higher yield (58.9%), drug loading (11.0% (w/w)) and encapsulation efficiency (33.5%), and also a controllable drug release profile. In order to evaluate the in vitro cytotoxicity of the prepared NPs, MTT assay was conducted, and results showed that the NPs could effectively inhibit HL60 and HepG2 cells with lower IC50 values compared with free curcumin. Furthermore, confocal microscopy together with flow cytometry analysis proved the enhanced apoptosis-inducing ability of PLGA-Cur NPs. Polymeric NP formulations are potential to be used for hydrophobic drug delivery systems in cancer therapy.

Poly(2-(diethylamino)ethyl methacrylate)-based, pH-responsive, copolymeric mixed micelles for targeting anticancer drug control release.

PubMed

Chen, Quan; Li, Siheng; Feng, Zixiong; Wang, Meng; Cai, Chengzhi; Wang, Jufang; Zhang, Lijuan

2017-01-01

We have demonstrated a novel drug delivery system to improve the selectivity of the current chemotherapy by pH-responsive, polymeric micelle carriers. The micelle carriers were prepared by the self-assembly of copolymers containing the polybasic poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) block. The mixed copolymers exhibited a comparatively low critical micelle concentration (CMC; 1.95-5.25 mg/L). The resultant mixed micelles were found to be <100 nm and were used to encapsulate the anticancer drug doxorubicin (DOX) with pretty good drug-loading content (24%) and entrapment efficiency (55%). Most importantly, the micelle carrier exhibited a pH-dependent conformational conversion and promoted the DOX release at the tumorous pH. Our in vitro studies demonstrated the comparable level of DOX-loaded mixed micelle delivery into tumor cells with the free DOX (80% of the tumor cells were killed after 48 h incubation). The DOX-loaded mixed micelles were effective to inhibit the proliferation of tumor cells after prolonged incubation. Overall, the pH-responsive mixed micelle system provided desirable potential in the controlled release of anticancer therapeutics.

Magnetic responsive of paclitaxel delivery system based on SPION and palmitoyl chitosan

NASA Astrophysics Data System (ADS)

Mansouri, Mona; Nazarpak, Masoumeh Haghbin; Solouk, Atefeh; Akbari, Somaye; Hasani-Sadrabadi, Mohammad Mahdi

2017-01-01

Concerns over cancer treatment have largely focused on chemotherapy and its consequent side effects. Utilizing nanocarriers is thought to be a panacea for mitigating the limitations of chemotherapy, and increasing its safety and efficacy. Magnetically driven Paclitaxel delivery systems are among the commonly investigated types of nanocarriers over the last two decades. In this context, we tried to highlight the application of an AC magnetic field and validate its consequential effects on drug delivery pattern and cell death in such nanodevices. So the aim of this study is to develop an appropriate matrix (Palmitoyl chitosan) co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) and anticancer drug, Paclitaxel (PTX) via the nanoprecipitation process. Synthesized nanoparticles were characterized by Dynamic Light Scattering (DLS) and their magnetic properties were investigated by Vibrating Sample Magnetometer (VSM). At initial loading of 10 wt% Paclitaxel, the maximum loading efficiency of nanoparticles with and without SPIONs was in the range of 69% and 72.3%, respectively. In addition, in vitro release data revealed that by the application of a magnetic field, release kinetic changed to the magnetic responsive pattern. Encapsulating anticancer drug in a synthesized nanosystem not only increased the amount of drug in cancer cells but also enhanced cell death (MCF-7) due to hyperthermic effects of SPIONs in the presence of an external magnetic field. In summary, these findings indicate that the resultant nanoparticles may serve as a biocompatible and biodegradable carrier for the precise delivery of powerful cytotoxic anticancer agents such as PTX.

Dual drug encapsulated thermo-sensitive fibrinogen-graft-poly (N-isopropyl acrylamide) nanogels for breast cancer therapy.

PubMed

Rejinold, N Sanoj; Baby, Thejus; Chennazhi, K P; Jayakumar, R

2014-02-01

5-FU/Megestrol acetate loaded fibrinogen-graft-PNIPAAm Nanogels (5-FU/Meg-fib-graft-PNIPAAm NGs) were prepared for thermo responsive drug delivery toward α5β1-integrins expressing breast cancer cells in vitro (MCF-7 cells). The 60-100 nm sized fib-graft-PNIPAAm nanogels (LCST=35 °C) were prepared by CaCl2 cross-linker. 5-FU/Meg-fib-graft-PNIPAAm NGs showed particle size of 165-195 nm size. The drug loading efficiency with 5-FU was 60% and 70% for Meg. "Drug release was greater above the lower critical solution temperature (LCST). Above LCST, drug release system triggers apopotosis and enhance toxicity to MCF-7 cells when compared to the equivalent dose of the free drug. This effect was due to the greater uptake of the drug by MCF-7 cells". 5-FU/Meg-fib-graft-PNIPAAm NGs is portrayed here as a new combinatorial thermo-responsive drug delivery agent for breast cancer therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

Characterization of folic acid-PAMAM conjugates: drug loading efficacy and dendrimer morphology.

PubMed

Chanphai, P; Tajmir-Riahi, H A

2018-05-01

We report the loading efficacy of folic acid (FA) by polyamidoamine (PAMAM-G3 and PAMAM-G4) nanoparticles in aqueous solution at physiological pH. Thermodynamic parameters ΔH = -47.57 (kJ Mol -1 ), ΔS = -122.78 (J Mol -1 , K -1 ) and ΔG = -10.96 (kJ Mol -1 ) showed FA-PAMAM bindings occur via H-bonding and van der Waals contacts. The stability of acid-PAMAM conjugate increased as polymer size increased. The acid loading efficacy was 40 to 50%. TEM images exhibited major polymer morphological changes upon acid encapsulation. PAMAM dendrimers are capable of FA delivery in vitro.

Surface modification of paclitaxel-loaded tri-block copolymer PLGA- b-PEG- b-PLGA nanoparticles with protamine for liver cancer therapy

NASA Astrophysics Data System (ADS)

Gao, Nansha; Chen, Zhihong; Xiao, Xiaojun; Ruan, Changshun; Mei, Lin; Liu, Zhigang; Zeng, Xiaowei

2015-08-01

In order to enhance the therapeutic effect of chemotherapy on liver cancer, a biodegradable formulation of protamine-modified paclitaxel-loaded poly(lactide- co-glycolide)- b-poly(ethylene glycol)- b-poly(lactide- co-glycolide) (PLGA- b-PEG- b-PLGA) nanoparticles (PTX-loaded/protamine NPs) was prepared. Tri-block copolymer PLGA- b-PEG- b-PLGA was synthesized by ring-opening polymerization and characterized by 1H NMR spectroscopy and gel permeation chromatography. PTX-loaded and PTX-loaded/protamine NPs were characterized in terms of size, size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin 6-loaded/protamine NPs were internalized by hepatocellular carcinoma cell line HepG2. The cellular uptake efficiency of NPs was obviously elevated after protamine modification. With commercial formulation Taxol® as the reference, HepG2 cells were also used to study the cytotoxicity of the NPs. PTX-loaded/protamine NPs exhibited significantly higher cytotoxicity than PTX-loaded NPs and Taxol® did. All the results suggested that surface modification of PTX-loaded PLGA- b-PEG- b-PLGA NPs with protamine boosted the therapeutic efficacy on liver cancer.

Hansen solubility parameters (HSP) for prescreening formulation of solid lipid nanoparticles (SLN): in vitro testing of curcumin-loaded SLN in MCF-7 and BT-474 cell lines.

PubMed

Doktorovova, Slavomira; Souto, Eliana B; Silva, Amélia M

2018-01-01

Curcumin, a phenolic compound from turmeric rhizome (Curcuma longa), has many interesting pharmacological effects, but shows very low aqueous solubility. Consequently, several drug delivery systems based on polymeric and lipid raw materials have been proposed to increase its bioavailability. Solid lipid nanoparticles (SLN), consisting of solid lipid matrix and a surfactant layer can load poorly water-soluble drugs, such as curcumin, deliver them at defined rates and enhance their intracellular uptake. In the present work, we demonstrate that, despite the drug's affinity to lipids frequently used in SLN production, the curcumin amount loaded in most SLN formulations may be too low to exhibit anticancer properties. The predictive curcumin solubility in solid lipids has been thoroughly analyzed by Hansen solubility parameters, in parallel with the lipid-screening solubility tests for a range of selected lipids. We identified the most suitable lipid materials for curcumin-loaded SLN, producing physicochemically stable particles with high encapsulation efficiency (>90%). Loading capacity of curcumin in SLN allowed preventing the cellular damage caused by cationic SLN on MCF-7 and BT-474 cells but was not sufficient to exhibit drug's anticancer properties. But curcumin-loaded SLN exhibited antioxidant properties, substantiating the conclusions that curcumin's effect in cancer cells is highly dose dependent.

Hydrogenated castor oil nanoparticles as carriers for the subcutaneous administration of tilmicosin: in vitro and in vivo studies.

PubMed

Han, C; Qi, C M; Zhao, B K; Cao, J; Xie, S Y; Wang, S L; Zhou, W Z

2009-04-01

Tilmicosin-loaded solid lipid nanoparticles (SLN) were prepared with hydrogenated castor oil (HCO) by o/w emulsion-solvent evaporation technique. The nanoparticle diameters, surface charges, drug loadings and encapsulation efficiencies of different formulations were 90 approximately 230 nm, -6.5 approximately -12.5 mV, 40.3 approximately 59.2% and 5.7 approximately 11.7% (w/w), respectively. In vitro release studies of the tilmicosin-loaded nanoparticles showed a sustained release and the released tilmicosin had the same antibacterial activity as that of the free drug. Pharmacokinetics study after subcutaneous administration to Balb/c mice demonstrated that a single dose of tilmicosin-loaded nanoparticles resulted in sustained serum drug levels (>0.1 microg/mL) for 8 days, as compared with only 5 h for the same amount of tilmicosin phosphate solution. The time to maximum concentration (Tmax), half-life of absorption (T(1/2) ab) and half-life of elimination (T(1/2) el) of tilmicosin-loaded nanoparticles were much longer than those of tilmicosin phosphate solution. Tissue section showed that drug-loaded nanoparticles caused no inflammation at the injection site. Cytotoxicity study in cell culture and acute toxicity test in mice demonstrated that the nanoparticles had little or no toxicity. The results of this exploratory study suggest that the HCO-SLN could be a useful system for the delivery of tilmicosin by subcutaneous administration.

Tamoxifen citrate loaded chitosan-gellan nanocapsules for breast cancer therapy: development, characterisation and in-vitro cell viability study.

PubMed

Kathle, Pankaj Kumar; Gautam, Nivedita; Kesavan, Karthikeyan

2018-06-08

The objective of this study was to evaluate the potential of chitosan-gellan nanocapsules (CGNCs) for encapsulation and sustained release of Tamoxifen citrate (TMC) for breast cancer therapy. Polyelectrolyte complex coacervation method was used for production of CGNCs. Interaction studies were conducted by Fourier-transform infra-red (FT-IR), differential scanning colorimetric (DSC), and X-ray diffraction (XRD) to investigate any interaction between drug and excipients. Physicochemical parameters, in vitro drug release and release kinetic were studied. In vitro cell viability study using Michigan Cancer Foundation-7 (MCF-7) breast cancer cells was also investigated. CGNCs had a smooth surface and nanosize range with a positive surface charge and exhibited sustained drug release. Further, TMC loaded CGNCs were found to be more cytotoxic than the free drug in MCF-7. Thus CGNCs may be suitable for breast cancer treatment due to delivering the drug at the site of action for a prolonged period of time.

Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia.

PubMed

Hamishehkar, Hamed; Ghanbarzadeh, Saeed; Sepehran, Sasan; Javadzadeh, Yousef; Adib, Zahra Mardhiah; Kouhsoltani, Maryam

2016-01-01

Flutamide is a potent anti-androgen with the several unwanted side effects in systemic administration, therefore, it has attracted special interest in the development of topically applied formulations for the treatment of androgenic alopecia. The purpose of this study was to prepare and characterize the solid lipid nanoparticles (SLNs) of Flutamide for follicular targeting in the treatment of the androgenic alopecia. Flutamide-loaded SLNs, promising drug carriers for topical application were prepared by hot melt homogenization method. Drug permeation and accumulation in the exercised rat skin and histological study on the male hamsters were performed to assess drug delivery efficiency in vitro and in vivo, respectively. The optimized Flutamide-loaded SLNs (size 198 nm, encapsulation efficiency percentage 65% and loading efficiency percentage 3.27%) exhibited a good stability during the period of at least 2 months. The results of X-ray diffraction showed Flutamide amorphous state confirming uniform drug dispersion in the SLNs structure. Higher skin drug deposition (1.75 times) of SLN formulation compared to Flutamide hydroalcoholic solution represented better localization of the drug in the skin. The in vivo studies showed more new hair follicle growth by utilizing Flutamide-loaded SLNs than Flutamide hydroalcoholic solution which could be due to the higher accumulation of SLNs in the hair follicles as well as slowly and continues release of the Flutamide through the SLNs maximizing hair follicle exposure by antiandrogenic drug. It was concluded Flutamide-loaded SLN formulation can be used as a promising colloidal drug carriers for topical administration of Flutamide in the treatment of androgenic alopecia.

Pantoprazole Sodium Loaded Microballoons for the Systemic Approach: In Vitro and In Vivo Evaluation.

PubMed

Gupta, Pravin; Kumar, Manish; Kaushik, Darpan

2017-09-01

Purpose: Various floating and pulsatile drug delivery systems suffer from variations in the gastric transit time affecting the bioavailability of drugs. The objective of the study was to develop Pantoprazole Sodium (PAN) microballoons that may prolong the gastric residence time and could enhance the drug bioavailability. Methods: Microballoons were prepared using Eudragit ® L100 by adopting emulsion solvent diffusion method with non-effervescent approach, in vitro studies were performed and the in vivo evaluation was carried out employing ethanol induced ulceration method. Optimization and validation were carried out through Design Expert ® software. Results: The results demonstrate an increase in percentage yield, buoyancy, encapsulation efficacy and swelling. Particles were in the size range 80-100 µm following zero order release pattern. SEM study revealed their rough surface with spherical shape, internal cavity and porous walls. DSC thermo gram confirms the encapsulation of drug in amorphous form. Significant anti ulcer activity was observed for the prepared microballoons. The calculated ulcer index and protection were 0.20±0.05 and 97.43 % respectively for LRS-O (optimized formulation). Conclusion: This kind of pH dependent drug delivery may provide an efficient dosage regimen with enhanced patient compliance.

Preparation and drug release properties of chitosan/organomodified palygorskite microspheres.

PubMed

Wu, Jie; Ding, Shijie; Chen, Jing; Zhou, Suqin; Ding, Hongyan

2014-07-01

The novel composite microspheres, based on the hybridization of chitosan (CS) and organomodified palygorskite (OPAL), were prepared by emulsion cross-linking technique and applied as a drug carrier. Palygorskite, a kind of natural one-dimensional clay, was modified with hexadecyl betaine (BS-16) to improve the compatibility and affinity with chitosan matrix, and worked as a perfect micron-filler to enhance drug encapsulation and retard drug migration. The structure of the microspheres was characterized by fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques. The swelling behavior of the microspheres and the effect of the amount of OPAL and BS-16 on the properties of the drug loading and releasing have been investigated. Compared to the pure chitosan microspheres (CM), the composite one with 20wt% OPAL modified by 20mmol/100g BS-16 possessed the higher encapsulation efficiency and the slower and continuous cumulative release for diclofenac sodium (DS) in phosphate buffer solution (pH 6.8). The study of drug release kinetics in vitro found that the drug release mechanism of the microspheres changed from the simple diffusion-control to diffusion and dissolution-control as the OPAL content in matrix increased from 0 to 20wt%. Copyright © 2014 Elsevier B.V. All rights reserved.

In vitro characterization of pH-sensitive azithromycin-loaded methoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) micelles.

PubMed

Teng, Fangfang; Deng, Peizong; Song, Zhimei; Zhou, Feilong; Feng, Runliang; Liu, Na

2017-06-15

In order to improve azithromycin's antibacterial activity in acidic medium, monomethoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) copolymer was synthesized through allylation, free radical addition, ring-opening polymerization and amidation reactions with methoxy poly (ethylene glycol) as raw material. Drug loading capacity and encapsulation efficiency of azithromycin-loaded micelles prepared via thin film hydration method were 11.58±0.86% and 96.06±1.93%, respectively. The drug-loaded micelles showed pH-dependent property in the respects of particle size, zeta potential at the range of pH 5.5-7.8. It could control drug in vitro release and demonstrate higher release rate at pH 6.0 than that at pH 7.4. In vitro antibacterial experiment indicated that the activity of azithromycin-loaded micelles against S. aureus was superior to free azithromycin in medium at both pH 6.0 and pH 7.4. Using fluorescein as substitute with pH-dependent fluorescence decrease property, laser confocal fluorescence microscopy analysis confirmed that cellular uptake of micelles was improved due to protonation of copolymer's imidazole groups at pH 6.0. The enhanced cellular uptake and release of drug caused its activity enhancement in acidic medium when compared with free drug. The micellar drug delivery system should be potential application in the field of bacterial infection treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2/M block in breast cancer cells.

PubMed

Verderio, Paolo; Bonetti, Paolo; Colombo, Miriam; Pandolfi, Laura; Prosperi, Davide

2013-03-11

PLGA nanoparticles are among the most studied polymer nanoformulations for several drugs against different kinds of malignant diseases, thanks to their in vivo stability and tumor localization exploiting the well-documented "enhanced permeation and retention" (EPR) effect. In this paper, we have developed uniform curcumin-bearing PLGA nanoparticles by a single-emulsion process, which exhibited a curcumin release following a Fickian-law diffusion over 10 days in vitro. PLGA nanoparticles were about 120 nm in size, as determined by dynamic light scattering, with a surface negative charge of -30 mV. The loading ratio of encapsulated drug in our PLGA nanoformulation was 8 wt%. PLGA encapsulation provided efficient protection of curcumin from environment, as determined by fluorescence emission experiments. Next, we have investigated the possibility to study the intracellular degradation of nanoparticles associated with a specific G2/M blocking effect on MCF7 breast cancer cells caused by curcumin release in the cytoplasm, which provided direct evidence on the mechanism of action of our nanocomplex. This study was carried out using Annexin V-based cell death analysis, MTT assessment of proliferation, flow cytometry, and confocal laser scanning microscopy. PLGA nanoparticles proved to be completely safe, suggesting a potential utilization of this nanocomplex to improve the intrinsically poor bioavailability of curcumin for the treatment of severe malignant breast cancer.

Transport Properties of Ibuprofen Encapsulated in Cyclodextrin Nanosponge Hydrogels: A Proton HR-MAS NMR Spectroscopy Study.

PubMed

Ferro, Monica; Castiglione, Franca; Punta, Carlo; Melone, Lucio; Panzeri, Walter; Rossi, Barbara; Trotta, Francesco; Mele, Andrea

2016-08-15

The chemical cross-linking of β-cyclodextrin (β-CD) with ethylenediaminetetraacetic dianhydride (EDTA) led to branched polymers referred to as cyclodextrin nanosponges (CDNSEDTA). Two different preparations are described with 1:4 and 1:8 CD-EDTA molar ratios. The corresponding cross-linked polymers were contacted with 0.27 M aqueous solution of ibuprofen sodium salt (IP) leading to homogeneous, colorless, drug loaded hydrogels. The systems were characterized by high resolution magic angle spinning (HR-MAS) NMR spectroscopy. Pulsed field gradient spin echo (PGSE) NMR spectroscopy was used to determine the mean square displacement (MSD) of IP inside the polymeric gel at different observation times td. The data were further processed in order to study the time dependence of MSD: MSD = f(td). The proposed methodology is useful to characterize the different diffusion regimes that, in principle, the solute may experience inside the hydrogel, namely normal or anomalous diffusion. The full protocols including the polymer preparation and purification, the obtainment of drug-loaded hydrogels, the NMR sample preparation, the measurement of MSD by HR-MAS NMR spectroscopy and the final data processing to achieve the time dependence of MSD are here reported and discussed. The presented experiments represent a paradigmatic case and the data are discussed in terms of innovative approach to the characterization of the transport properties of an encapsulated guest within a polymeric host of potential application for drug delivery.

Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation.

PubMed

Mohsen, Amira Mohamed; AbouSamra, Mona Mahmoud; ElShebiney, Shaimaa Ahmed

2017-08-01

This study was designed to investigate the potency of niosomes, for glimepiride (GLM) encapsulation, aiming at enhancing its oral bioavailability and hypoglycemic efficacy. Niosomes containing nonionic surfactants (NIS) were prepared by thin film hydration technique and characterized. In-vitro release study was performed using a dialysis technique. In-vivo pharmacodynamic studies, as well as pharmacokinetic evaluation were performed on alloxan-induced diabetic rats. GLM niosomes exhibited high-entrapment efficiency percentages (E.E. %) up to 98.70% and a particle size diameter ranging from 186.8 ± 18.69 to 797.7 ± 12.45 nm, with negatively charged zeta potential (ZP). Different GLM niosomal formulation showed retarded in vitro release, compared to free drug. In-vivo studies revealed the superiority of GLM niosomes in lowering blood glucose level (BGL) and in maintaining a therapeutic level of GLM for a longer period of time, as compared to free drug and market product. There was no significant difference between mean plasma AUC 0-48 hr of GLM-loaded niosomes and that of market product. GLM-loaded niosomes exhibited seven-fold enhancement in relative bioavailability in comparison with free drug. These findings reinforce the potential use of niosomes for enhancing the oral bioavailability and prolonged delivery of GLM via oral administration.

pH-responsive unimolecular micelles self-assembled from amphiphilic hyperbranched block copolymer for efficient intracellular release of poorly water-soluble anticancer drugs.

PubMed

Tabatabaei Rezaei, Seyed Jamal; Abandansari, Hamid Sadeghi; Nabid, Mohammad Reza; Niknejad, Hassan

2014-07-01

Novel unimolecular micelles from amphiphilic hyperbranched block copolymer H40-poly(ε-caprolactone)-b-poly(acrylic acid)-b'-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate (i.e., H40-PCL-b-PAA-b'-MPEG/PEG-FA (HCAE-FA)) as new multifunctional nanocarriers to pH-induced accelerated release and tumor-targeted delivery of poorly water-soluble anticancer drugs were developed. The hydrophobic core of the unimolecular micelle was hyperbranched polyester (H40-poly(ε-caprolactone) (H40-PCL)). The inner hydrophilic layer was composed of PAA segments, while the outer hydrophilic shell was composed of PEG segments. This copolymer formed unimolecular micelles in the aqueous solution with a mean particle size of 33 nm, as determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). To study the feasibility of micelles as a potential nanocarrier for targeted drug delivery, we encapsulated a hydrophobic anticancer drug, paclitaxel (PTX), in the hydrophobic core, and the loading content was determined by UV-vis analysis to be 10.35 wt.%. In vitro release studies demonstrated that the drug-loaded delivery system is relatively stable at physiologic conditions but susceptible to acidic environments which would trigger the release of encapsulated drugs. Flow cytometry and fluorescent microscope studies revealed that the cellular binding of the FA-conjugated micelles against HeLa cells was higher than that of the neat micelles (without FA). The in vitro cytotoxicity studies showed that the PTX transported by these micelles was higher than that by the commercial PTX formulation Tarvexol®. All of these results show that these unique unimolecular micelles may offer a very promising approach for targeted cancer therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.

PubMed

Wu, Daocheng; Wan, Mingxi

2008-01-01

Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.

Development of drug-loaded chitosan-vanillin nanoparticles and its cytotoxicity against HT-29 cells.

PubMed

Li, Pu-Wang; Wang, Guang; Yang, Zi-Ming; Duan, Wei; Peng, Zheng; Kong, Ling-Xue; Wang, Qing-Huang

2016-01-01

Chitosan as a natural polysaccharide derived from chitin of arthropods like shrimp and crab, attracts much interest due to its inherent properties, especially for application in biomedical materials. Presently, biodegradable and biocompatible chitosan nanoparticles are attractive for drug delivery. However, some physicochemical characteristics of chitosan nanoparticles still need to be further improved in practice. In this work, chitosan nanoparticles were produced by crosslinking chitosan with 3-methoxy-4-hydroxybenzaldehyde (vanillin) through a Schiff reaction. Chitosan nanoparticles were 200-250 nm in diameter with smooth surface and were negatively charged with a zeta potential of - 17.4 mV in neutral solution. Efficient drug loading and drug encapsulation were achieved using 5-fluorouracil as a model of hydrophilic drug. Drug release from the nanoparticles was constant and controllable. The in vitro cytotoxicity against HT-29 cells and cellular uptake of the chitosan nanoparticles were evaluated by methyl thiazolyl tetrazolium method, confocal laser scanning microscope and flow cytometer, respectively. The results indicate that the chitosan nanoparticles crosslinked with vanillin are a promising vehicle for the delivery of anticancer drugs.

Techniques for loading technetium-99m and rhenium-186/188 radionuclides into pre-formed liposomes for diagnostic imaging and radionuclide therapy.

PubMed

Goins, Beth; Bao, Ande; Phillips, William T

2010-01-01

Liposomes can serve as carriers of radionuclides for diagnostic imaging and therapeutic applications. Herein, procedures are outlined for radiolabeling liposomes with the gamma-emitting radionuclide, technetium-99m ((99m)Tc), for non-invasive detection of disease and for monitoring the pharmacokinetics and biodistribution of liposomal drugs, and/or with therapeutic beta-emitting radionuclides, rhenium-186/188 ((186/188)Re), for radionuclide therapy. These efficient and practical liposome radiolabeling methods use a post-labeling mechanism to load (99m)Tc or (186/188)Re into pre-formed liposomes prepared in advance of the labeling procedure. For all liposome radiolabeling methods described, a lipophilic chelator is used to transport (99m)Tc or (186/188)Re across the lipid bilayer of the pre-formed liposomes. Once within the liposome interior, the pre-encapsulated glutathione or ammonium sulfate (pH) gradient provides for stable entrapment of the (99m)Tc and (186/188)Re within the liposomes. In the first method, (99m)Tc is transported across the lipid bilayer by the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO) and (99m)Tc-HMPAO becomes trapped by interaction with the pre-encapsulated glutathione within the liposomes. In the second method, (99m)Tc or (186/188)Re is transported across the lipid bilayer by the lipophilic chelator, N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), and (99m)Tc-BMEDA or (186/188)Re-BMEDA becomes trapped by interaction with pre-encapsulated glutathione within the liposomes. In the third method, an ammonium sulfate (pH) gradient loading technique is employed using liposomes with an extraliposomal pH of 7.4 and an interior pH of 5.1. BMEDA, which is lipophilic at pH 7.4, serves as a lipophilic chelator for (99m)Tc or (186/188)Re to transport the radionuclides across the lipid bilayer. Once within the more acidic liposome interior, (99m)Tc/(186/188)Re-BMEDA complex becomes protonated and more hydrophilic, which results in stable entrapment of the (99m)Tc/(186/188)Re-BMEDA complex within the liposomes. Since many commercially available liposomal drugs use an ammonium sulfate (pH) gradient for drug loading, these liposomal drugs can be directly radiolabeled with (99m)Tc-BMEDA for non-invasive monitoring of tissue distribution during treatment or with (186/188)Re-BMEDA for combination chemo-radionuclide therapy.

Encapsulation of lycopene in Chlorella pyrenoidosa: Loading properties and stability improvement.

PubMed

Pu, Chuanfen; Tang, Wenting

2017-11-15

Aiming to improve the stability of lycopene and incorporate it into a complex nutraceutical, exogenous lycopene-loaded Chlorella pyrenoidosa cells (CPCs) were developed. The complex had an encapsulation yield of 13.06±0.89% and an encapsulation efficiency of 96.31±3.10%. Fluorescence analyses indicated that lycopene was encapsulated in the CPCs. X-ray diffraction, thermogravimetric and differential scanning calorimetric analyses were conducted and compared to those of the non-loaded CPCs, lycopene and their physical mixture. These studies demonstrated that lycopene was amorphous in the complex. The degradation kinetics indicated that encapsulation increased the stability of lycopene. The antioxidant activity of lycopene loaded CPCs against DPPH free radicals was higher than that of the unencapsulated lycopene after storage at 25°C for 25d. This study proved the feasibility of encapsulation of lycopene in the CPCs and combined the activities of both materials, which could be employed in the production of novel nutraceuticals to reduce oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Co-delivery of cisplatin and paclitaxel by folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles for the treatment of non-small lung cancer.

PubMed

He, Zelai; Huang, Jingwen; Xu, Yuanyuan; Zhang, Xiangyu; Teng, Yanwei; Huang, Can; Wu, Yufeng; Zhang, Xi; Zhang, Huijun; Sun, Wenjie

2015-12-08

An amphiphilic copolymer, folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) was prepared and explored as a nanometer carrier for the co-delivery of cisplatin (cis-diaminodichloroplatinum, CDDP) and paclitaxel (PTX). CDDP and PTX were encapsulated inside the hydrophobic inner core and chelated to the middle shell, respectively. PEG provided the outer corona for prolonged circulation. An in vitro release profile of the CDDP + PTX-encapsulated nanoparticles revealed that the PTX chelation cross-link prevented an initial burst release of CDDP. After an incubation period of 24 hours, the CDDP+PTX-encapsulated nanoparticles exhibited a highly synergistic effect for the inhibition of A549 (FA receptor negative) and M109 (FA receptor positive) lung cancer cell line proliferation. Pharmacokinetic experiment and distribution research shows that nanoparticles have longer circulation time in the blood and can prolong the treatment times of chemotherapeutic drugs. For the in vivo treatment of A549 cells xeno-graft lung tumor, the CDDP+PTX-encapsulated nanoparticles displayed an obvious tumor inhibiting effect with an 89.96% tumor suppression rate (TSR). This TSR was significantly higher than that of free chemotherapy drug combination or nanoparticles with a single drug. For M109 cells xeno-graft tumor, the TSR was 95.03%. In vitro and in vivo experiments have all shown that the CDDP+PTX-encapsulated nanoparticles have better targeting and antitumor effects in M109 cells than CDDP+PTX-loaded PEG-PLGA nanoparticles (p < 0.05). In addition, more importantly, the enhanced anti-tumor efficacy of the CDDP+PTX-encapsulated nanoparticles came with reduced side-effects. No obvious body weight loss or functional changes occurred within blood components, liver, or kidneys during the treatment of A549 and M109 tumor-bearing mice with the CDDP+PTX-encapsulated nanoparticles. Thus, the FA modified amphiphilic copolymer-based combination of CDDP and PTX may provide useful guidance for effective and safe cancer chemotherapy, especially in tumors with high FA receptor expression.

Application of arteether-loaded polyurethane nanomicelles to induce immune response in breast cancer model.

PubMed

Jabbarzadegan, Mona; Rajayi, Hajar; Mofazzal Jahromi, Mirza Ali; Yeganeh, Hamid; Yousefi, Mehdi; Muhammad Hassan, Zuhair; Majidi, Jafar

2017-06-01

To concentrate a potent anticancer drug (Arteether) in tumor microenvironment, we encapsulated it in biodegradable and pH sensitive polyurethane (PU) nanomicelles (NMs). The nanocomplex was characterized by Fourier transform infrared (FTIR), dynamic light scattering (DLS). The loading capacity and release profile in pH of 5.4 and 7.4 were considered. The cytotoxicity effect was evaluated in vitro and in vivo settings. The level of IFN-γ and IL-4 cytokines of mice splenocytes were assessed by enzyme-linked immunosorbent assay (ELISA). The nanocomplex showed negative zeta charge of -26.2 mV, size of 42.30 nm and high loading capacity (92%). Release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4. It indicated significant inhibitory effect on the growth of 4T1 cell line and increased IFN-γ level.

Covalent and non-covalent curcumin loading in acid-responsive polymeric micellar nanocarriers

NASA Astrophysics Data System (ADS)

Gao, Min; Chen, Chao; Fan, Aiping; Zhang, Ju; Kong, Deling; Wang, Zheng; Zhao, Yanjun

2015-07-01

Poor aqueous solubility, potential degradation, rapid metabolism and elimination lead to low bioavailability of pleiotropic impotent curcumin. Herein, we report two types of acid-responsive polymeric micelles where curcumin was encapsulated via both covalent and non-covalent modes for enhanced loading capacity and on-demand release. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a hydrazone linker, generating two conjugates differing in architecture (single-tail versus double-tail) and free curcumin was encapsulated therein. The two micelles exhibited similar hydrodynamic size at 95 ± 3 nm (single-tail) and 96 ± 3 nm (double-tail), but their loading capacities differed significantly at 15.0 ± 0.5% (w/w) (single-tail) and 4.8 ± 0.5% (w/w) (double-tail). Under acidic sink conditions (pH 5.0 and 6.0), curcumin displayed a faster release from the single-tail nanocarrier, which was correlated to a low IC50 of 14.7 ± 1.6 (μg mL-1) compared to the value of double-tail micelle (24.9 ± 1.3 μg mL-1) in HeLa cells. The confocal imaging and flow cytometry analysis demonstrated a superior capability of single-tail micelle for intracellular curcumin delivery, which was a consequence of the higher loading capacity and lower degree of mPEG surface coverage. In conclusion, the dual loading mode is an effective means to increase the drug content in the micellar nanocarriers whose delivery efficiency is highly dependent on its polymer-drug conjugate architecture. This strategy offers an alternative nanoplatform for intracellularly delivering impotent hydrophobic agents (i.e. curcumin) in an efficient stimuli-triggered way, which is valuable for the enhancement of curcumin’s efficacy in managing a diverse range of disorders.

Remote loading of doxorubicin into liposomes driven by a transmembrane phosphate gradient.

PubMed

Fritze, Andreas; Hens, Felicitas; Kimpfler, Andrea; Schubert, Rolf; Peschka-Süss, Regine

2006-10-01

This study examines a new method for the remote loading of doxorubicin into liposomes. It was shown that doxorubicin can be loaded to a level of up to 98% into large unilamellar vesicles composed of egg phosphatidylcholine/cholesterol (7/3 mol/mol) with a transmembrane phosphate gradient. The different encapsulation efficiencies which were achieved with ammonium salts (citrate 100%, phosphate 98%, sulfate 95%, acetate 77%) were significantly higher as compared to the loading via sodium salts (citrate 54%, phosphate 52%, sulfate 44%, acetate 16%). Various factors, including pH-value, buffer capacity, solubility of doxorubicin in different salt solutions and base counter-flow, which likely has an influence on drug accumulation in the intraliposomal interior are taken into account. In contrast to other methods, the newly developed remote loading method exhibits a pH-dependent drug release property which may be effective in tumor tissues. At physiological pH-value doxorubicin is retained in the liposomes, whereas drug release is achieved by lowering the pH to 5.5 (approximately 25% release at 25 degrees C or 30% at 37 degrees C within two h). The DXR release of liposomes which were loaded via a sulfate gradient showed a maximum of 3% at pH 5.5.

Effect of liquid-to-solid lipid ratio on characterizations of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for transdermal administration.

PubMed

Song, Aihua; Zhang, Xiaoshu; Li, Yanting; Mao, Xinjuan; Han, Fei

2016-08-01

The aim of this study is to evaluate the effect of liquid-to-solid lipid ratio on properties of flurbiprofen-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), and to clarify the superiority of NLCs over SLNs for transdermal administration. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, differential scanning calorimetry, X-ray diffractometry, in vitro percutaneous permeation profile, and stability of SLNs and NLCs were compared. Particle size, zeta potential, drug encapsulation efficiency, in vitro occlusion factor, and in vitro percutaneous permeation amount of the developed NLCs were all <200 nm, < -20 mV, >78%, >35, and >240 μg/cm(2), respectively, however, for SLNs were 280 nm, -29.11 mV, 63.2%, 32.54, and 225.9 μg/cm(2), respectively. After 3 months storage at 4 °C and 25 °C, almost no significant differences between the evaluated parameters of NLCs were observed. However, for SLNs, particle size was increased to higher than 300 nm (4 °C and 25 °C), drug encapsulation efficiency was decreased to 51.2 (25 °C), in vitro occlusion factor was also decreased to lower than 25 (4 °C and 25 °C), and the cumulative amount was decreased to 148.9 μg/cm(2) (25 °C) and 184.4 μg/cm(2) (4 °C), respectively. And DSC and XRD studies indicated that not only the crystalline peaks of the encapsulated flurbiprofen disappeared but also obvious difference between samples and bulk Compritol® ATO 888 was seen. It could be concluded that liquid-to-solid lipid ratio has significant impact on the properties of SLNs and NLCs, and NLCs showed better stability than SLNs. Therefore, NLCs might be a better option than SLNs for transdermal administration.

Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

PubMed Central

2012-01-01

Background Alpha 1- antitrypsin (α1AT) belongs to the superfamily of serpins and inhibits different proteases. α1AT protects the lung from cellular inflammatory enzymes. In the absence of α1AT, the degradation of lung tissue results to pulmonary complications. The pulmonary route is a potent noninvasive route for systemic and local delivery. The aerosolized α1AT not only affects locally its main site of action but also avoids remaining in circulation for a long period of time in peripheral blood. Poly (D, L lactide-co glycolide) (PLGA) is a biodegradable and biocompatible polymer approved for sustained controlled release of peptides and proteins. The aim of this work was to prepare a wide range of particle size as a carrier of protein-loaded nanoparticles to deposit in different parts of the respiratory system especially in the deep lung. Various lactide to glycolide ratio of the copolymer was used to obtain different release profile of the drug which covers extended and rapid drug release in one formulation. Results Nonaqueous and double emulsion techniques were applied for the synthesis of nanoparticles. Nanoparticles were characterized in terms of surface morphology, size distribution, powder X-ray diffraction (XRD), encapsulation efficiency, in vitro drug release, FTIR spectroscopy and differential scanning calorimetry (DSC). To evaluate the nanoparticles cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human epithelial lung cancer cell line. Nanoparticles were spherical with an average size in the range of 100 nm to 1μ. The encapsulation efficiency was found to be higher when the double emulsion technique was applied. XRD and DSC results indicated that α1AT encapsulated in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The lactic acid to glycolic acid ratio affects the release profile of α1AT. Hence, PLGA with a 50:50 ratios exhibited the ability to release %60 of the drug within 8, but the polymer with a ratio of 75:25 had a continuous and longer release profile. Cytotoxicity studies showed that nanoparticles do not affect cell growth and were not toxic to cells. Conclusion In summary, α1AT-loaded nanoparticles may be considered as a novel formulation for efficient treatment of many pulmonary diseases. PMID:22607686

Curcumin-loaded polymeric nanoparticles for enhanced anti-colorectal cancer applications.

PubMed

Udompornmongkol, Panisa; Chiang, Been-Huang

2015-11-01

The purpose of the present study was to fabricate polymeric nanoparticles as drug carriers for encapsulated curcumin with enhanced anti-colorectal cancer applications. Nanoparticles were formulated from chitosan and gum arabic, natural polysaccharides, via an emulsification solvent diffusion method. The formation of curcumin nanoparticles was confirmed by Fourier transform infrared spectroscopy and differential scanning calorimeter. The results show that curcumin was entrapped in carriers with +48 mV, 136 nm size, and high encapsulation efficiency (95%). Based on an in vitro release study, we inferred that curcumin nanoparticles could tolerate hydrolysis due to gastric juice or small intestinal enzymes, and therefore, it should reach the colon largely intact. In addition, curcumin nanoparticles had higher anti-colorectal cancer properties than free curcumin due to greater cellular uptake. Therefore, we concluded that curcumin was successfully encapsulated in chitosan-gum arabic nanoparticles with superior anti-colorectal cancer activity. © The Author(s) 2015.

Magnetic polymer microcapsules loaded with Nile Red fluorescent dye

NASA Astrophysics Data System (ADS)

Bartel, Marta; Wysocka, Barbara; Krug, Pamela; Kępińska, Daria; Kijewska, Krystyna; Blanchard, Gary J.; Kaczyńska, Katarzyna; Lubelska, Katarzyna; Wiktorska, Katarzyna; Głowala, Paulina; Wilczek, Marcin; Pisarek, Marcin; Szczytko, Jacek; Twardowski, Andrzej; Mazur, Maciej

2018-04-01

Fabrication of multifunctional smart vehicles for drug delivery is a fascinating challenge of multidisciplinary research at the crossroads of materials science, physics and biology. We demonstrate a prototypical microcapsule system that is capable of encapsulating hydrophobic molecules and at the same time reveals magnetic properties. The microcapsules are prepared using a templated synthesis approach where the molecules to be encapsulated (Nile Red) are present in the organic droplets that are suspended in the polymerization solution which also contains magnetic nanoparticles. The polymer (polypyrrole) grows on the surface of organic droplets encapsulating the fluorescent dye in the core of the formed microcapsule which incorporates the nanoparticles into its wall. For characterization of the resulting structures a range of complementary physicochemical methodology is used including optical and electron microscopy, magnetometry, 1H NMR and spectroscopy in the visible and X-ray spectral ranges. Moreover, the microcapsules have been examined in biological environment in in vitro and in vivo studies.

In situ forming biodegradable poly(ε-caprolactone) microsphere systems: a challenge for transarterial embolization therapy. In vitro and preliminary ex vivo studies.

PubMed

Salis, Andrea; Porcu, Elena P; Gavini, Elisabetta; Fois, Giulia R; Icaro Cornaglia, Antonia; Rassu, Giovanna; Diana, Marco; Maestri, Marcello; Giunchedi, Paolo; Nikolakakis, Ioannis

2017-04-01

In situ forming biodegradable poly(ε-caprolactone) (PCL) microspheres (PCL-ISM) system was developed as a novel embolic agent for transarterial embolization (TAE) therapy of hepatocellular carcinoma (HCC). Ibuprofen sodium (Ibu-Na) was loaded on this platform to evaluate its potential for the treatment of post embolization syndrome. The influence of formulation parameters on the size/shape, encapsulation efficiency and drug release was investigated using mixture experimental design. Regression models were derived and used to optimize the formulation for particle size, encapsulation efficiency and drug release profile for TAE therapy. An ex vivo model using isolated rat livers was established to assess the in situ formation of microspheres. All PCL-ISM components affected the studied properties and fitting indices of the regression models were high (Radj 2  = 0.810 for size, 0.964 encapsulation efficiency, and 0.993 or 0.971 for drug release at 30 min or 48 h). The optimized composition was: PCL = 4%, NMP = 43.1%, oil = 48.9%, surfactant = 2% and drug = 2%. Ex vivo studies revealed that PCL-ISM was able to form microspheres in the hepatic arterial bed. PCL-ISM system provides a novel tool for the treatment of HCC and post-embolization syndrome. It is capable of forming microspheres with desirable size and Ibu-Na release profile after injection into blood vessels.

Preparation of curcumin-loaded pluronic F127/chitosan nanoparticles for cancer therapy

NASA Astrophysics Data System (ADS)

Phuc Le, Thi Minh; Phuc Pham, Van; Lua Dang, Thi Minh; Huyen La, Thi; Hanh Le, Thi; Huan Le, Quang

2013-06-01

Nanoparticles (NPs) have been proven to be an effective delivery system with few side effects for anticancer drugs. In this study, curcumin-loaded NPs have been prepared by an ionic gelation method using chitosan (Chi) and pluronic®F-127 (PF) as carriers to deliver curcumin to the target cancer cells. Prepared NPs were characterized using Zetasizer, fluorescence microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Our results showed that the encapsulation efficiency of curcumin was approximately 50%. The average size of curcumin-loaded PF/Chi NPs was 150.9 nm, while the zeta potential was 5.09 mV. Cellular uptake of curcumin-loaded NPs into HEK293 cells was confirmed by fluorescence microscopy.

Halloysite nanotubes as carriers of vancomycin in alginate-based wound dressing.

PubMed

Kurczewska, Joanna; Pecyna, Paulina; Ratajczak, Magdalena; Gajęcka, Marzena; Schroeder, Grzegorz

2017-09-01

The influence of an inorganic support - halloysite nanotubes - on the release rate and biological activity of the antibiotic encapsulated in alginate-based dressings was studied. The halloysite samples were loaded with approx. 10 wt.% of the antibiotic and then encapsulated in Alginate and Gelatin/Alginate gels. The material functionalized with aliphatic amine significantly extended the release of vancomycin from alginate-based gels as compared to that achieved when silica was used. After 24 h, the released amounts of the antibiotic immobilized at silica reached 70%, while for the drug immobilized at halloysite the released amount of vancomycin reached 44% for Alginate discs. The addition of gelatin resulted in even more prolonged sustained release of the drug. The antibiotic was released from the system with a double barrier with Higuchi kinetic model and Fickian diffusion mechanism. Only the immobilized drug encapsulated in Alginate gel demonstrated very good antimicrobial activity against various bacteria. The inhibition zones were greater than those of the standard discs for the staphylococci and enterococci bacteria tested. The addition of gelatin adversely affected the biological activity of the system. The inhibition zones were smaller than those of the reference samples. A reduction in the drug dose by half had no significant effect on changing the release rate and microbiological activity. The in vivo toxicity studies of the material with immobilized drug were carried out with Acutodesmus acuminatus and Daphnia magna . The material studied had no effect on the living organisms used in the bioassays. The proposed system with a double barrier demonstrated high storage stability.

Pharmacokinetics of intramuscular microparticle depot of valdecoxib in an experimental model.

PubMed

Agnihotri, Sagar M; Vavia, Pradeep R

2009-09-01

We did a prospective study to investigate pharmacokinetics of a single intramuscularly (i.m.) administered Valdecoxib (VC) polymeric microparticles in New Zealand white rabbits. Poly[lac(glc-leu)] microparticles encapsulating a potent cyclooxygenase-2- selective inhibitor, VC, were prepared by emulsion and solvent evaporation technique and administered i.m. to rabbits for pharmacokinetic study. A single i.m. dose of drug-loaded poly[lac(glc-leu)] microparticles resulted in sustained therapeutic drug levels in the plasma for 49 days. The relative bioavailability was increased severalfold as compared with unencapsulated drug. Injectable poly[lac(glc-leu)] microparticles hold promise for increasing drug bioavailability and reducing dosing frequency for better management of rheumatoid arthritis.

Novel docetaxel-loaded nanoparticles based on poly(lactide-co-caprolactone) and poly(lactide-co-glycolide-co-caprolactone) for prostate cancer treatment: formulation, characterization, and cytotoxicity studies

NASA Astrophysics Data System (ADS)

Sanna, Vanna; Roggio, Anna Maria; Posadino, Anna Maria; Cossu, Annalisa; Marceddu, Salvatore; Mariani, Alberto; Alzari, Valeria; Uzzau, Sergio; Pintus, Gianfranco; Sechi, Mario

2011-12-01

Docetaxel (Dtx) chemotherapy is the optional treatment in patients with hormone-refractory metastatic prostate cancer, and Dtx-loaded polymeric nanoparticles (NPs) have the potential to induce durable clinical responses. However, alternative formulations are needed to overcome the serious side effects, also due to the adjuvant used, and to improve the clinical efficacy of the drug. In the present study, two novel biodegradable block-copolymers, poly(lactide-co-caprolactone) (PLA-PCL) and poly(lactide-co-caprolactone-co-glycolide) (PLGA-PCL), were explored for the formulation of Dtx-loaded NPs and compared with PLA- and PLGA-NPs. The nanosystems were prepared by an original nanoprecipitation method, using Pluronic F-127 as surfactant agent, and were characterized in terms of morphology, size distribution, encapsulation efficiency, crystalline structure, and in vitro release. To evaluate the potential anticancer efficacy of a nanoparticulate system, in vitro cytotoxicity studies on human prostate cancer cell line (PC3) were carried out. NPs were found to be of spherical shape with an average diameter in the range of 100 to 200 nm and a unimodal particle size distribution. Dtx was incorporated into the PLGA-PCL NPs with higher ( p < 0.05) encapsulation efficiency than that of other polymers. Differential scanning calorimetry suggested that Dtx was molecularly dispersed in the polymeric matrices. In vitro drug release study showed that release profiles of Dtx varied on the bases of characteristics of polymers used for formulation. PLA-PCL and PLGA-PCL drug loaded NPs shared an overlapping release profiles, and are able to release about 90% of drug within 6 h, when compared with PLA- and PLGA-NPs. Moreover, cytotoxicity studies demonstrated advantages of the Dtx-loaded PLGA-PCL NPs over pure Dtx in both time- and concentration-dependent manner. In particular, an increase of 20% of PC3 growth inhibition was determined by PLGA-PCL NPs with respect to free drug after 72 h incubation and at all tested Dtx concentration. In summary, PLGA-PCL copolymer may be considered as an attractive and promising polymeric material for the formulation of Dtx NPs as delivery system for prostate cancer treatment, and can also be pursued as a validated system in a more large context.

Design and in vivo evaluation of solid lipid nanoparticulate systems of Olanzapine for acute phase schizophrenia treatment: Investigations on antipsychotic potential and adverse effects.

PubMed

Joseph, Emil; Reddi, Satish; Rinwa, Vibhu; Balwani, Garima; Saha, Ranendra

2017-06-15

The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29±3.36nm) with very high encapsulation efficiency (74.51±1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems was maintained for 48h as compared to 8h antipsychotic action of pure Olanzapine solution. The weight gain studies for 28days demonstrated a significant inhibition in weight gain for Olanzapine-loaded nanoparticulate systems as compared to the pure Olanzapine. The present research findings indicate that OLN-loaded nanoparticulate systems may be highly promising for effective delivery of Olanzapine with better efficacy and minimum adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanocarriers from GRAS Zein Proteins to Encapsulate Hydrophobic Actives.

PubMed

Weissmueller, Nikolas T; Lu, Hoang D; Hurley, Amanda; Prud'homme, Robert K

2016-11-14

One factor limiting the expansion of nanomedicines has been the high cost of the materials and processes required for their production. We present a continuous, scalable, low cost nanoencapsulation process, Flash Nanoprecipitation (FNP) that enables the production of nanocarriers (NCs) with a narrow size distribution using zein corn proteins. Zein is a low cost, GRAS protein (having the FDA status of "Generally Regarded as Safe") currently used in food applications, which acts as an effective encapsulant for hydrophobic compounds using FNP. The four-stream FNP configuration allows the encapsulation of very hydrophobic compounds in a way that is not possible with previous precipitation processes. We present the encapsulation of several model active compounds with as high as 45 wt % drug loading with respect to zein concentration into ∼100 nm nanocarriers. Three examples are presented: (1) the pro-drug antioxidant, vitamin E-acetate, (2) an anticholera quorum-sensing modulator CAI-1 ((S)-3-hydroxytridecan-4-one; CAI-1 that reduces Vibrio cholerae virulence by modulating cellular communication), and (3) hydrophobic fluorescent dyes with a range of hydrophobicities. The specific interaction between zein and the milk protein, sodium caseinate, provides stabilization of the NCs in PBS, LB medium, and in pH 2 solutions. The stability and size changes in the three media provide information on the mechanism of assembly of the zein/active/casein NC.

Mucoadhesive buccal tablets containing silymarin Eudragit-loaded nanoparticles: formulation, characterisation and ex vivo permeation.

PubMed

El-Nahas, Amira E; Allam, Ahmed N; El-Kamel, Amal H

2017-08-01

Eudragit-loaded silymarin nanoparticles (SNPs) and their formulation into buccal mucoadhesive tablets were investigated to improve the low bioavailability of silymarin through buccal delivery. Characterisation of SNPs and silymarin buccal tablets (SBTs) containing the optimised NPs were performed. Ex vivo permeability of nominated SBTs were assessed using chicken pouch mucosa compared to SNPs and drug suspension followed by histopathological examination. Selected SNPs had a small size (<150 nm), encapsulation effciency (>77%) with drug release of about 90% after 6 h. For STBs, all physicochemical parameters were satisfactory for different polymers used. DSC and FT-IR studies suggested the presence of silymarin in an amorphous state. Ex vivo permeation significantly emphasised the great enhancement of silymarin permeation after NPs formation and much more increase after formulating into BTs relative to the corresponding drug dispersion with confirmed membrane integrity. Incorporation of SNPs into BTs could be an efficient vehicle for delivery of silymarin.

Polymer Nanocarriers to Enhance the Efficiency of Platinum-Based Chemotherapeutics

NASA Astrophysics Data System (ADS)

Callari, Manuela

The aim of this Thesis was to design and prepare polymer nanocarriers capable of encapsulating, carrying and delivering platinum-based chemotherapeutics. Polymer nanocarrier have been widely studied and employed as platinum drug delivery systems with the primary scope to overcome limitations presented by platinum-based chemotherapeutics. The conjugation of platinum onto polymers, however, presents some challenges, and, although there has been great progress in the field of drug delivery in the past years, to date only three polymer nanocarriers for platinum drugs have found their way to the clinic. In this Thesis, hydrophilic block copolymers were synthesised via reversible addition fragmentation chain transfer (RAFT) polymerisation or N-carboxyanhydride ring-opening polymerization (NCA-ROP). Upon attachment of a hydrophobic platinum drug the block copolymer becomes amphiphilic and can self-assemble in aqueous media into nanoparticles of different morphology depending on the block copolymer features. Spherical micelles consisting of a poly(methacrylic acid) core which conjugates and encapsulates the platinum chemotherapeutic and a hydrophilic shell made of sugar blocks were prepared and their biological activities compared in vitro. Among the sugars considered here, fructose based micelles showed promising results in terms of their targeting ability towards breast cancer cells. Consequently, fructose-shelled micelles were selected to explore the effect of different loading quantities of platinum drug. It was discovered that the amount of platinum in the core of the micelle highly influences the internal morphology of the micelle which, in turn, affects the micelle-cell interactions. Micelles with low dual drug loading had better cellular uptake and higher toxicity than the micelles with high drug loading, despite having the same fructose-based outer shell. Interestingly, this aspect had been neglected by literature so far, and is important to explore. Micelles made of a fructose shell were then compared to micelles with a non-targeting hydrophilic shell made of poly(ethylene glycol) methyl ether methacrylate (PEGMEMA). The aim was to compare the process of cellular uptake and the mechanism of platinum release inside the cell. For this scope, a fluorescent platinum drug was synthesised as a probing tool. Finally, a polymer vesicle based on PEG and poly(glutamic acid) was designed to co-deliver a platinum drug and the cancer inhibitor, paclitaxel, simultaneously. The two drugs have a synergistic effect when used in combination or co-delivered by the vesicles. Moreover, a viability study using multicellular tumour spheroids (MCTS) showed a significant decrease in cell proliferation when the MCTS were treated with single drug, a combination of free drugs and dual-drug loaded vesicles compared with untreated MCTS. An improvement is observed in the case of the dual-drug vesicles.

Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer

NASA Astrophysics Data System (ADS)

Gao, Xiang; Wang, Bilan; Wei, Xiawei; Men, Ke; Zheng, Fengjin; Zhou, Yingfeng; Zheng, Yu; Gou, Maling; Huang, Meijuan; Guo, Gang; Huang, Ning; Qian, Zhiyong; Wei, Yuquan

2012-10-01

Encapsulation of hydrophobic agents in polymer micelles can improve the water solubility of cargos, contributing to develop novel drugs. Quercetin (QU) is a hydrophobic agent with potential anticancer activity. In this work, we encapsulated QU into biodegradable monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles and tried to provide proof-of-principle for treating ovarian cancer with this nano-formulation of quercetin. These QU loaded MPEG-PCL (QU/MPEG-PCL) micelles with drug loading of 6.9% had a mean particle size of 36 nm, rendering the complete dispersion of quercetin in water. QU inhibited the growth of A2780S ovarian cancer cells on a dose dependent manner in vitro. Intravenous administration of QU/MPEG-PCL micelles significantly suppressed the growth of established xenograft A2780S ovarian tumors through causing cancer cell apoptosis and inhibiting angiogenesis in vivo. Furthermore, the anticancer activity of quercetin on ovarian cancer cells was studied in vitro. Quercetin treatment induced the apoptosis of A2780S cells associated with activating caspase-3 and caspase-9. MCL-1 downregulation, Bcl-2 downregulation, Bax upregulation and mitochondrial transmembrane potential change were observed, suggesting that quercetin may induce apoptosis of A2780S cells through the mitochondrial apoptotic pathway. Otherwise, quercetin treatment decreased phosphorylated p44/42 mitogen-activated protein kinase and phosphorylated Akt, contributing to inhibition of A2780S cell proliferation. Our data suggested that QU/MPEG-PCL micelles were a novel nano-formulation of quercetin with a potential clinical application in ovarian cancer therapy.

Biological evaluation of N-2-hydroxypropyl trimethyl ammonium chloride chitosan as a carrier for the delivery of live Newcastle disease vaccine.

PubMed

Zhao, Kai; Sun, Yanwei; Chen, Gang; Rong, Guangyu; Kang, Hong; Jin, Zheng; Wang, Xiaohua

2016-09-20

Mucosal immune system plays a very important role in antiviral immune response. We prepared Newcastle disease viruses (NDV) encapsulated in N-2-hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC) nanoparticles (NDV/La Sota-N-2-HACC-NPs) by an ionic cross linking method, and assessed the potential of N-2-HACC-NPs as a mucosal immune delivery carrier. The properties of the nanoparticles were determined by transmission electron microscopy, Zeta potential and particle size analysis, encapsulation efficiency and loading capacity. NDV/La Sota-N-2-HACC-NPs have regular spherical morphologies and high stability; with 303.88±49.8nm mean diameter, 45.77±0.75mV Zeta potential, 94.26±0.42% encapsulation efficiency and 54.06±0.21% loading capacity. In vitro release assay indicated that the release of NDV from NDV/La Sota-N-2-HACC-NPs is slow. The NDV/La Sota-N-2-HACC-NPs have good biological characteristics, very low toxicity and high level of safety. Additionally, specific pathogen-free chickens immunized with NDV/La Sota-N-2-HACC-NPs showed much stronger cellular, humoral and mucosal immune responses than commercial attenuated live Newcastle disease vaccine, and NDV/La Sota-N-2-HACC-NPs reached the sustainable release effect. Our study here provides a foundation for the further development of mucosal vaccines and drugs, and the N-2-HACC-NPs should be a potential drug delivery carrier with immense potential in medical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of synthetic zeolites as oral delivery vehicle for anti-inflammatory drugs

PubMed Central

Khodaverdi, Elham; Honarmandi, Reza; Alibolandi, Mona; Baygi, Roxana Rafatpanah; Hadizadeh, Farzin; Zohuri, Gholamhossein

2014-01-01

Objective(s): In this research, zeolite X and zeolite Y were used as vehicle to prepare intestine targeted oral delivery systems of indomethacin and ibuprofen. Materials and Methods: A soaking procedure was implemented to encapsulate indomethacin or ibuprofen within synthetic zeolites. Gravimetric methods and IR spectra of prepared formulations were used to assess drug loading efficiencies into zeolite structures. Scanning Electron Microscopy (SEM) was also utilized to determine morphologies changes in synthetic zeolites after drug loading. At the next stage, dissolution studies were used to predict the in vivo performance of prepared formulations at HCl 0.1 N and PBS pH 6.5 as simulated gastric fluid (SGF) and simulated intestine fluid (SIF), respectively. Results: Drug loadings of prepared formulations was determined between 24-26 % w/w. Dissolution tests at SGF were shown that zeolites could retain acidic model drugs in their porous structures and can be able to limit their release into the stomach. On the other hand, all prepared formulations completely released model drugs during 3 hr in simulated intestine fluid. Conclusion: Obtained results indicated zeolites could potentially be able to release indomethacin and ibuprofen in a sustained and controlled manner and reduced adverse effects commonly accompanying oral administrations of NSAIDs. PMID:24967062

Improved hepatoprotective activity of silymarin via encapsulation in the novel vesicular nanosystem bilosomes.

PubMed

Mohsen, Amira Mohamed; Asfour, Marwa Hasanein; Salama, Abeer A A

2017-12-01

The main objective of the present work was to formulate, characterize, and evaluate silymarin (SM)-loaded bilosomes, compared to conventional liposomes, aiming at increasing the hepatoprotective activity of the drug. SM-loaded bilosomes were prepared by thin film hydration technique employing soybean phosphatidyl choline (SPC) and different bile salts. After being subjected to different methods of characterization, SM-loaded bilosomes were investigated for their hepatoprotective activity, in CCl 4 hepatointoxicated rat model. The developed SM dispersions exhibited an entrapment efficiency ranging from 21.80 ± 2.01 to 84.54 ± 2.51% and a particle size diameter in the nanometric dimensions (413 ± 96.9 to 686.9 ± 62.38 nm), with a negative zeta potential values (<-45 mV). In vitro release study revealed a lower cumulative amount of drug released from the developed formulae, compared to free drug. Ex vivo intestinal uptake study, performed using confocal laser scanning calorimetry, revealed the superiority of bilosomal uptake compared to that of liposomes. In vivo studies revealed an enhanced hepatoprotective effect of SM-loaded bilosomes/liposomes compared to free drug. These results were in good correlation with histopathological examination. These findings support the potential use of bilosomes for improving the hepatoprotective activity of SM via oral administration.

Chitosan-based nanocomplexes for simultaneous loading, burst reduction and controlled release of doxorubicin and 5-fluorouracil.

PubMed

Di Martino, Antonio; Kucharczyk, Pavel; Capakova, Zdenka; Humpolicek, Petr; Sedlarik, Vladimir

2017-09-01

In this work, nanocomplexes based on chitosan grafted by carboxy-modified polylactic acid (SPLA) were prepared with the aim of loading simultaneously two anticancer drugs - doxorubicin and 5-fluorouracil, as well as to control their release, reduce the initial burst and boost cytotoxicity. The SPLA was prepared by a polycondensation reaction, using pentetic acid as the core molecule, and linked to the chitosan backbone through a coupling reaction. Nanocomplexes loaded with both drugs were formulated by the polyelectrolyte complexation method. The structure of the SPLA was characterized by 1 H NMR, while the product CS-SPLA was analyzed by FTIR-ATR to prove the occurrence of the reaction. Results showed that the diameters and ζ-potential of the nanocomplexes fall in the range 120-200nm and 20-37mV, respectively. SEM and TEM analysis confirmed the spherical shape and dimensions of the nanocomplexes. The presence of hydrophobic side chain SPLA did not influence the encapsulation efficiency of the drugs but strongly reduced the initial burst and prolonged release over time compared to unmodified chitosan. MS analysis showed that no degradation or interactions between the drugs and carrier were exhibited after loading or 24h of release had taken place, confirming the protective role of the nanocomplexes. In vitro tests demonstrated an increase in the cytotoxicity of the drugs when loaded in the prepared carriers. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

pH-responsive supramolecular vesicles based on water-soluble pillar[6]arene and ferrocene derivative for drug delivery.

PubMed

Duan, Qunpeng; Cao, Yu; Li, Yan; Hu, Xiaoyu; Xiao, Tangxin; Lin, Chen; Pan, Yi; Wang, Leyong

2013-07-17

The drug delivery system based on supramolecular vesicles that were self-assembled by a novel host-guest inclusion complex between a water-soluble pillar[6]arene (WP6) and hydrophobic ferrocene derivative in water has been developed. The inclusion complexation between WP6 and ferrocene derivative in water was studied by (1)H NMR, UV-vis, and fluorescence spectroscopy, which showed a high binding constant of (1.27 ± 0.42) × 10(5) M(-1) with 1:1 binding stoichiometry. This resulting inclusion complex could self-assemble into supramolecular vesicles that displayed a significant pH-responsive behavior in aqueous solution, which were investigated by fluorescent probe technique, dynamic laser scattering, and transmission electron microscopy. Furthermore, the drug loading and in vitro drug release studies demonstrated that these supramolecular vesicles were able to encapsulate mitoxantrone (MTZ) to achieve MTZ-loaded vesicles, which particularly showed rapid MTZ release at low-pH environment. More importantly, the cellular uptake of these pH-responsive MTZ-loaded vesicles by cancer cells was observed by living cell imaging techniques, and their cytotoxicity assay indicated that unloaded vesicles had low toxicity to normal cells, which could dramatically reduce the toxicity of MTZ upon loading of MTZ. Meanwhile, MTZ-loaded vesicles exhibited comparable anticancer activity in vitro as free MTZ to cancer cells under examined conditions. This study suggests that such supramolecular vesicles have great potential as controlled drug delivery systems.

Combined photothermo-chemotherapy using gold nanoshells on drug-loaded micelles for colorectal cancer treatment

NASA Astrophysics Data System (ADS)

Lee, Shin-Yu; Shieh, Ming-Jium

2018-02-01

Combined photothermo-chemotherapy is a new strategy for cancer treatment which improves the therapeutic outcome by synergistic effects of both therapies. Here, we presented a multifunctional gold nanoshell that exhibited excellent photothermal conversion and delivered the hydrophobic chemotherapy drug, SN-38. The positively charged SN-38-loaded PDMA-PCL micelles were decorated with a gold layer by in situ reduction of chloroauric acid on the surface of micelles. Scanning and transmission electron microscopy images proved micelles were successfully decorated and the resulting gold nanoshells had a spherical morphology with a narrow size distribution. The synthesized gold nanoshells displayed a broad surface plasmon resonance peak in the near-infrared wavelength region and a great photothermal conversion ability. After pegylation, gold nanoshells were stable in biological media and appeared highly biocompatible in the absence of laser irradiation. Upon near-infrared laser irradiation, incident energy was converted into heat by gold nanoshells on SN-38-loaded micelles (SN-38@pGNS), which causes local temperature increase and triggers the release of encapsulated drug. Compared to SN-38, SN-38-loaded micelles, or laser with drug-free gold nanoshells alone, combined photothermo-chemotherapy using SN-38@pGNS with laser irradiation killed colorectal cancer cells with higher efficacy in vitro and demonstrated significant tumor suppression in vivo, suggesting that gold nanoshells on drug-loaded micelles delivered SN-38 and photothermal therapy in synergistic actions and might be a potential candidate for future colorectal cancer therapy.

Encapsulation of an adamantane-doxorubicin prodrug in pH-responsive polysaccharide capsules for controlled release.

PubMed

Luo, Guo-Feng; Xu, Xiao-Ding; Zhang, Jing; Yang, Juan; Gong, Yu-Hui; Lei, Qi; Jia, Hui-Zhen; Li, Cao; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2012-10-24

Supramolecular microcapsules (SMCs) with the drug-loaded wall layers for pH-controlled drug delivery were designed and prepared. By using layer-by-layer (LbL) technique, the SMCs were constructed based on the self-assembly between polyaldenhyde dextran-graft-adamantane (PAD-g-AD) and carboxymethyl dextran-graft-β-CD (CMD-g-β-CD) on CaCO(3) particles via host-guest interaction. Simultaneously, adamantine-modified doxorubicin (AD-Dox) was also loaded on the LbL wall via host-guest interaction. The in vitro drug release study was carried out at different pHs. Because the AD groups were linked with PAD (PAD-g-AD) or Dox (AD-Dox) by pH-cleavable hydrazone bonds, AD moieties can be removed under the weak acidic condition, leading to destruction of SMCs and release of Dox. The pH-controlled drug release can enhance the uptake by tumor cells and thus achieve improved cancer therapy efficiency.

Hollow Fe₃O₄/Graphene Oxide Nanocomposites as Novel Rapamycin Carrier: Formulation Optimization and In Vitro Characterization.

PubMed

Cao, Liangli; Jiang, Yuren; Chen, Zhencheng

2018-05-01

In the present research an attempt was made to develop and optimize rapamycin (Rapa) loaded hollow magnetic Fe3O4/graphene oxide (Fe3O4/GO) nanocomposites using solvent evaporation technique and response surface methodology (RSM). A Box-Behnken design (BBD) with a three-level, three-factor was used to determine preparation parameters that would achieve the highest encapsulation efficiency (EE) and drug loading capacity (DLC). At optimum conditions such as mass ratio of Rapa to Fe3O4/GO (Rapa: Fe3O4/GO) 0.45, oscillation rate 144.0, and volume ratio of water to solvent (W/S) 4.2, the EE and DLC of experimentally prepared particles reached 84.92 ± 5.50% and 28.68 ± 2.54% respectively. The morphological assessment results showed that hollow Fe3O4 nano-aggregates were evenly and tightly dispersed on the layer of GO membrane. After the addition of GO and encapsulation of Rapa, the Fe3O4/GO nanocomposites and Rapa loaded magnetic Fe3O4/GO (Fe3O4/GO-Rapa) nanocomposites showed saturation magnetization of 57.77 and 40.71 emu/g respectively. The drug releasing experiment indicated a slightly acidic atmosphere, which was suitable for Rapa releasing from the obtained Fe3O4/GO nanocomposites. The cell counting Kit-8 (CCK-8) assays demonstrated the hollow Fe3O4/GO nanocomposites could effectively improve the efficacy of Rapa in killing HepG2 cells, which displayed a concentration-dependent manner. All these results suggested the prepared Fe3O4/GO nanocomposites have a potential application in drug delivery system.

Preparation and Characterization of Three Tilmicosin-loaded Lipid Nanoparticles: Physicochemical Properties and in-vitro Antibacterial Activities.

PubMed

Al-Qushawi, Alwan; Rassouli, Ali; Atyabi, Fatemeh; Peighambari, Seyed Mostafa; Esfandyari-Manesh, Mehdi; Shams, Gholam Reza; Yazdani, Azam

2016-01-01

Tilmicosin (TLM) is an important antibiotic in veterinary medicine with low bioavailability and safety. This study aimed to formulate and evaluate physicochemical properties, storage stability after lyophilization, and antibacterial activity of three TLM-loaded lipid nanoparticles (TLM-LNPs) including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid-core nanocapsules (LNCs). Physicochemical parameters such as particle size-mean diameter, polydispersity index, zeta potential, drug encapsulation efficiency (EE), loading capacity, and morphology of the formulations were evaluated and the effects of various cryoprotectants during lyophilization and storage for 8 weeks were also studied. The profiles of TLM release and the antibacterial activities of these TLM-LNPs suspensions (against Escherichia coli and Staphylococcus aureus ) were tested in comparison with their corresponding powders. TLM-LNPs suspensions were in nano-scale range with mean diameters of 186.3 ± 1.5, 149.6 ± 3.0, and 85.0 ± 1.0nm, and also EE, 69.1, 86.3, and 94.3% for TLM- SLNs, TLM-NLCs, and TLM- LNCs respectively. TLM-LNCs gave the best results with significantly low particle size and high EE (p<0.05). Mannitol was the most effective cryoprotectant for lyophilization and storage of TLM-LNPs. The drug release profiles were biphasic and the release times were longer at pH 7.4 where TLM-NLCs and TLM-LNCs powders showed longer release times. In microbiological tests, S. aureus was about 4 times more sensitive than E. coli to TLM-LNPs with minimum inhibitory concentration ranges of 0.5-1.0 and 2-4 µg/mL respectively, and TLM-LNCs exhibited the best antibacterial activities. In conclusion, TLM-LNP formulations especially TLM-LNCs and TLM-NLCs are promising carriers for TLM with better drug encapsulation capacity, release behavior, and antibacterial activity.

PLGA nanoparticles for the oral delivery of 5-Fluorouracil using high pressure homogenization-emulsification as the preparation method and in vitro/in vivo studies.

PubMed

Li, XueMing; Xu, YuanLong; Chen, GuoGuang; Wei, Ping; Ping, QiNeng

2008-01-01

The objective of the present study was to incorporate the hydrophilic anti-cancer drug 5-Fluorouracil(5-FU) into poly(lactide-co-glycolide) (PLGA) nanoparticles(NP) to improve the oral bioavailability. Owing to the high solubility of 5-FU in basic water, the water-in-oil-in-water (w/o/w) emulsification process has been chosen as one of the most appropriate method for the encapsulation of 5-FU, and the ammonia solution was used as the inner aqueous phase solvent to increase the solubility of 5-FU. In order to reach submicron size as well as increasing the grade of monodispersity compared to previous preparation techniques, we prepared 5-FU loaded PLGA-NP by a high-pressure emulsification-solvent evaporation process. The PLGA-NPs were characterized with respect to their morphology, particle size, size distribution, 5-FU encapsulation efficiency, in vitro and in vivo studies in rats. In vitro release of 5-FU from nanoparticles appeared to have two components with an initial rapid release due to the surface associated drug and followed by a slower exponential release of 5-FU, which was dissolved in the core. The in vivo research was studied in male Sprague-Dawley rats after an oral 5-FU dose of 45 mg/kg. Single oral administration of 5-FU loaded PLGA-NP to rats produced bioavailability, which was statistically higher than 5-FU solution as negative control. And the MRT (mean residence time) of 5-FU loaded PLGA-NP was significantly (P < 0.05) modified. Thus, it is possible to design a controlled drug delivery system for oral 5-FU delivery, improving therapy efficiency by possible reduction of time intervals between peroral administrations and reduction of local gastrointestinal side effects.

Smart polyelectrolyte microcapsules as carriers for water-soluble small molecular drug.

PubMed

Song, Weixing; He, Qiang; Möhwald, Helmuth; Yang, Yang; Li, Junbai

2009-10-15

Heat treatment is introduced as a simple method for the encapsulation of low molecular weight water-soluble drugs within layer-by-layer assembled microcapsules. A water-soluble drug, procainamide hydrochloride, could thus be encapsulated in large amount and enriched by more than 2 orders of magnitude in the assembled PDADMAC/PSS capsules. The shrunk capsules could control the unloading rate of drugs, and the drugs could be easily unloaded using ultrasonic treatment. The encapsulated amount could be quantitatively controlled via the drug concentration in the bulk. We also found that smaller capsules possess higher encapsulation capability.

Preparation of Robust Metal-Free Magnetic Nanoemulsions Encapsulating Low-Molecular-Weight Nitroxide Radicals and Hydrophobic Drugs Directed Toward MRI-Visible Targeted Delivery.

PubMed

Nagura, Kota; Takemoto, Yusa; Moronaga, Satori; Uchida, Yoshiaki; Shimono, Satoshi; Shiino, Akihiko; Tanigaki, Kenji; Amano, Tsukuru; Yoshino, Fumi; Noda, Yohei; Koizumi, Satoshi; Komatsu, Naoki; Kato, Tatsuhisa; Yamauchi, Jun; Tamura, Rui

2017-11-07

With a view to developing a theranostic nanomedicine for targeted drug delivery systems visible by magnetic resonance (MR) imaging, robust metal-free magnetic nanoemulsions (mean particle size less than 20 nm) consisting of a biocompatible surfactant and hydrophobic, low molecular weight 2,2,5-trimethyl-5-(4-alkoxy)phenylpyrrolidine-N-oxyl radicals were prepared in pH 7.4 phosphate-buffered saline (PBS). The structure of the nanoemulsions was characterized by electron paramagnetic resonance spectroscopy, and dynamic light scattering and small-angle neutron-scattering measurements. The nanoemulsions showed high colloidal stability, low cytotoxicity, enough reduction resistance to excess ascorbic acid, and sufficient contrast enhancement in the proton longitudinal relaxation time (T 1 ) weighted MR images in PBS in vitro (and preliminarily in vivo). Furthermore, the hydrophobic anticancer drug paclitaxel could be encapsulated inside the nanoparticles, and the resulting paclitaxel-loaded nanoemulsions were efficiently incorporated into HeLa cells to suppress cell growth. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stimulus-responsive zinc oxide-functionalized macromolecular humic acid nanocarrier for enhancement of antibacterial activity of ciprofloxacin hydrochloride.

PubMed

Murugesan, Gowri; Latha, Nachimuthu; Suganya, Kannan; Murugan, Marudhamuthu; Munusamy, Murugan A; Rajan, Mariappan

2018-07-15

Macromolecular of naturally occurring humic acid (HA) have garnered interest in the chemical, biological and medicine industry owing to their unique behavior, i.e., strong adsorptive and non-toxic nature. Here, we investigated the functionalization of organic (HA) with inorganic (ZnO) hybrid nanoparticles for topical and site-targeted delivery of ciprofloxacin by simple emulsification techniques. Ciprofloxacin (CIPRO)-encapsulated hybrid nanocarrier constitute an attractive novel drug delivery vehicle for sustained release of antibiotics to bacterial infection sites in an extended and controlled manner. The analytical characteristics of the designed system were thoroughly investigated by FTIR, XRD, SEM/EDAX, and TEM. The drug release of ciprofloxacin over 24h was 87.5%, 98.03%, 97.44%, and 97.24% for pH2.5, 5.5, 6.8, and 8.0, respectively. The antibacterial activities results confirmed that the CIPRO-encapsulated hybrid nanocarrier showed excellent growth inhibition against microorganisms. This hybrid nanocarrier loaded with antibiotics represents a promising approach for targeted and controlled drug delivery to infected sites. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of squalane on mebendazole-loaded Compritol® nanoparticles.

PubMed

Graves, Richard A; Ledet, Grace A; Nation, Cedric A; Pramar, Yashoda V; Bostanian, Levon A; Mandal, Tarun K

2015-01-01

The objective of this study is to develop nanostructured lipid formulations of Compritol for the delivery of mebendazole. The formulations were prepared with Compritol 888 ATO, squalane, and Pluronic F68. Nine batches with different amounts of modifier, squalane, and drug were prepared. The formulations were characterized by evaluating particle size, morphology, and zeta potential. The thermal properties of the formulations were analyzed by differential scanning calorimetry (DSC). The encapsulation efficiency of each formulation and the drug release rates from each formulation were quantified by UPLC. The particles were spherical and had median particle sizes between 300 and 600 nm (50th percentile). A linear relationship was observed between Compritol/squalane composition and the melting point of the mixture. The DSC scans of the formulations revealed some recrystallization of the drug from the formulations, and the amount of recrystallization correlated with the amount of squalane in the formulation. Approximately, 70% efficiency of encapsulation was observed in the formulations with 30% (w/w) squalane, and these formulations also had faster dissolution rates compared to the other formulations. Overall, the formulations with 30% squalane are the preferred formulation for future testing.

Nanopharmaceutics: phytochemical-based controlled or sustained drug-delivery systems for cancer treatment.

PubMed

Jeetah, Roubeena; Bhaw-Luximon, Archana; Jhurry, Dhanjay

2014-09-01

This review is an attempt to assess the different classes of phytochemicals and some of their members which have been encapsulated into nanocarrier systems for their chemotherapeutic or chemopreventive properties. Given the broad spectrum of nanomedicines currently in clinical trial and clinical use from polymer-protein conjugates, through nanocrystals, nanogels, dendrimers to ethosomes, the focus of this review will be on block copolymer nanomicelles, nanoparticles, polymer-drug conjugates, liposomes and solid lipid nanocarriers (SLNs). The twenty phytochemicals investigated for encapsulation and targeted delivery were selected from a variety of classes intended to encompass the largest possible chemical compositions, namely flavonoids, aromatic acids, xanthones, terpenes, quinones, lignans and alkaloids. To the best of our knowledge, reviews on the nanoencapsulation of these phytochemicals and their delivery are not available. In this review, the issues associated with the limited use of each phytochemical in cancer therapy in humans are reviewed and the advantages of entrapment into nanocarriers are assessed in terms of drug loading efficiency, size of nanocarriers, drug release profiles and in vitro and/or in vivo testing specific to cancer research, e.g., cytotoxicity assay, cell inhibition/viability, scavenging of reactive oxygen species and biodistribution studies (elimination half-life and mean residence time).

Preparation of anastrozole loaded PEG-PLA nanoparticles: evaluation of apoptotic response of breast cancer cell lines.

PubMed

Alyafee, Yusra A; Alaamery, Manal; Bawazeer, Shahad; Almutairi, Mansour S; Alghamdi, Badr; Alomran, Nawaf; Sheereen, Atia; Daghestani, Maha; Massadeh, Salam

2018-01-01

Anastrozole (ANS) is an aromatase inhibitor that is widely used as a treatment for breast cancer in postmenopausal women. Despite the wide use of ANS, it is associated with serious side effects due to uncontrolled delivery. In addition, ANS exhibits low solubility and short plasma half-life. Nanotechnology-based drug delivery has the potential to enhance the efficacy of drugs and overcome undesirable side effects. In this study, we aimed to prepare novel ANS-loaded PLA-PEG-PLA nanoparticles (ANS-NPs) and to compare the apoptotic response of MCF-7 cell line to both ANS and ANS-loaded NPs. ANS-NPs were synthesized using double emulsion method and characterized using different methods. The apoptotic response was evaluated by assessing cell viability, morphology, and studying changes in the expression of MAPK3 , MCL1 , and c-MYC apoptotic genes in MCF-7 cell lines. ANS was successfully encapsulated within PLA-PEG-PLA, forming monodisperse therapeutic NPs with an encapsulation efficiency of 67%, particle size of 186±27.13, and a polydispersity index of 0.26±0.11 with a sustained release profile extended over 144 hours. In addition, results for cell viability and for gene expression represent a similar apoptotic response between the free ANS and ANS-NPs. The synthesized ANS-NPs showed a similar therapeutic effect as the free ANS, which provides a rationale to pursue pre-clinical evaluation of ANS-NPs on animal models.

The Effect of Polymeric Nanoparticles on Biocompatibility of Carrier Red Blood Cells

PubMed Central

Pan, Daniel; Vargas-Morales, Omayra; Zern, Blaine; Anselmo, Aaron C.; Gupta, Vivek; Zakrewsky, Michael; Mitragotri, Samir; Muzykantov, Vladimir

2016-01-01

Red blood cells (RBCs) can be used for vascular delivery of encapsulated or surface-bound drugs and carriers. Coupling to RBC prolongs circulation of nanoparticles (NP, 200 nm spheres, a conventional model of polymeric drug delivery carrier) enabling their transfer to the pulmonary vasculature without provoking overt RBC elimination. However, little is known about more subtle and potentially harmful effects of drugs and drug carriers on RBCs. Here we devised high-throughput in vitro assays to determine the sensitivity of loaded RBCs to osmotic stress and other damaging insults that they may encounter in vivo (e.g. mechanical, oxidative and complement insults). Sensitivity of these tests is inversely proportional to RBC concentration in suspension and our results suggest that mouse RBCs are more sensitive to damaging factors than human RBCs. Loading RBCs by NP at 1:50 ratio did not affect RBCs, while 10–50 fold higher NP load accentuated RBC damage by mechanical, osmotic and oxidative stress. This extensive loading of RBC by NP also leads to RBCs agglutination in buffer; however, addition of albumin diminished this effect. These results provide a template for analyses of the effects of diverse cargoes loaded on carrier RBCs and indicate that: i) RBCs can tolerate carriage of NP at doses providing loading of millions of nanoparticles per microliter of blood; ii) tests using protein-free buffers and mouse RBCs may overestimate adversity that may be encountered in humans. PMID:27003833

Novel chitosan derivative for temperature and ultrasound dual-sensitive liposomal microbubble gel.

PubMed

Chen, Daquan; Yu, Hongyun; Mu, Hongjie; Wei, Junhua; Song, Zhenkun; Shi, Hong; Liang, Rongcai; Sun, Kaoxiang; Liu, Wanhui

2013-04-15

In this study, a novel liposome-loaded microbubble gel based on N-cholesteryl hemisuccinate-O-sulfate chitosan (NCHOSC) was designed. The structure of the NCHOSC was characterized by FTIR and (1)H NMR. The liposomal microbubble gel based on NCHOSC with a high encapsulation efficiency of curcumin was formed and improved the solubility of curcumin. The diameter of most liposomal microbubble was about 950 nm. The temperature-sensitive CS/GP gel could be formulated at room temperature and would form a gel at body temperature. Simultaneously, the ultrasound-sensitive induced release of curcumin was 85% applying ultrasound. The results of cytotoxicity assay indicated that encapsulated curcumin in Cur-LM or Cur-LM-G was less toxic. The anti-tumor efficacy in vivo suggested that Cur-LM-G by ultrasound suppressed tumor growth most efficiently. These findings have shed some light on the potential NCHOSC material used to liposome-loaded microbubble gel for temperature and ultrasound dual-sensitive drug delivery. Copyright © 2013 Elsevier Ltd. All rights reserved.

A novel diblock of copolymer of (monomethoxy poly [ethylene glycol]-oleate) with a small hydrophobic fraction to make stable micelles/polymersomes for curcumin delivery to cancer cells

PubMed Central

Erfani-Moghadam, Vahid; Nomani, Alireza; Zamani, Mina; Yazdani, Yaghoub; Najafi, Farhood; Sadeghizadeh, Majid

2014-01-01

Curcumin is a potent natural anticancer agent, but its effectiveness is limited by properties such as very low solubility, high rate of degradation, and low rate of absorption of its hydrophobic molecules in vivo. To date, various nanocarriers have been used to improve the bioavailability of this hydrophobic biomaterial. This study investigates the encapsulation of curcumin in a novel nanostructure of monomethoxy poly(ethylene glycol)-oleate (mPEG-OA) and its anticancer effect. Tests were done to determine the critical micelle concentration (CMC), encapsulation efficiency, drug-loading efficiency, and cytotoxicity (against U87MG brain carcinoma cells and HFSF-PI3 cells as normal human fibroblasts) of some nanodevice preparations. The results of fluorescence microscopy and cell-cycle analyses indicated that the in vitro bioavailability of the encapsulated curcumin was significantly greater than that of free curcumin. Cytotoxicity evaluations showed that half maximal inhibitory concentrations of free curcumin and curcumin-loaded mPEG-OA for the U87MG cancer cell line were 48 μM and 24 μM, respectively. The Annexin-V-FLUOS assay was used to quantify the apoptotic effect of the prepared nanostructures. Apoptosis induction was observed in a dose-dependent manner after curcumin-loaded mPEG-OA treatments. Two common self-assembling structures, micelles and polymersomes, were observed by atomic force microscopy and dynamic light scattering, and the abundance of each structure was dependent on the concentration of the diblock copolymer. The mPEG-OA micelles had a very low CMC (13.24 μM or 0.03 g/L). Moreover, atomic force microscopy and dynamic light scattering showed that the curcumin-loaded mPEG-OA polymersomes had very stable structures, and at concentrations 1,000 times less than the CMC, at which the micelles disappear, polymersomes were the dominant structures in the dispersion with a reduced size distribution below 150 nm. Overall, the results from these tests revealed that this nanocarrier can be considered as an appropriate drug delivery system for delivering curcumin to cancer cells. PMID:25489242

Controlling chitosan-based encapsulation for protein and vaccine delivery

PubMed Central

Koppolu, Bhanu prasanth; Smith, Sean G.; Ravindranathan, Sruthi; Jayanthi, Srinivas; Kumar, Thallapuranam K.S.; Zaharoff, David A.

2014-01-01

Chitosan-based nano/microencapsulation is under increasing investigation for the delivery of drugs, biologics and vaccines. Despite widespread interest, the literature lacks a defined methodology to control chitosan particle size and drug/protein release kinetics. In this study, the effects of precipitation-coacervation formulation parameters on chitosan particle size, protein encapsulation efficiency and protein release were investigated. Chitosan particle sizes, which ranged from 300 nm to 3 μm, were influenced by chitosan concentration, chitosan molecular weight and addition rate of precipitant salt. The composition of precipitant salt played a significant role in particle formation with upper Hofmeister series salts containing strongly hydrated anions yielding particles with a low polydispersity index (PDI) while weaker anions resulted in aggregated particles with high PDIs. Sonication power had minimal effect on mean particle size, however, it significantly reduced polydispersity. Protein loading efficiencies in chitosan nano/microparticles, which ranged from 14.3% to 99.2%, was inversely related to the hydration strength of precipitant salts, protein molecular weight and directly related to the concentration and molecular weight of chitosan. Protein release rates increased with particle size and were generally inversely related to protein molecular weight. This study demonstrates that chitosan nano/microparticles with high protein loading efficiencies can be engineered with well-defined sizes and controllable release kinetics through manipulation of specific formulation parameters. PMID:24560459

Polydopamine-Functionalized CA-(PCL-ran-PLA) Nanoparticles for Target Delivery of Docetaxel and Chemo-photothermal Therapy of Breast Cancer

PubMed Central

Kong, Na; Deng, Mei; Sun, Xiu-Na; Chen, Yi-Ding; Sui, Xin-Bing

2018-01-01

Current limitations of cancer therapy include the lack of effective strategy for target delivery of chemotherapeutic drugs, and the difficulty of achieving significant efficacy by single treatment. Herein, we reported a synergistic chemo-photothermal strategy based on aptamer (Apt)-polydopamine (pD) functionalized CA-(PCL-ran-PLA) nanoparticles (NPs) for effective delivery of docetaxel (DTX) and enhanced therapeutic effect. The developed DTX-loaded Apt-pD-CA-(PCL-ran-PLA) NPs achieved promising advantages, such as (i) improved drug loading content (LC) and encapsulation efficiency (EE) initiated by star-shaped copolymer CA-(PCL-ran-PLA); (ii) effective target delivery of drugs to tumor sites by incorporating AS1411 aptamers; (iii) significant therapeutic efficacy caused by synergistic chemo-photothermal treatment. In addition, the pD coating strategy with simple procedures could address the contradiction between targeting modification and maintaining formerly excellent bio-properties. Therefore, with excellent bio-properties and simple preparation procedures, the DTX-loaded Apt-pD-CA-(PCL-ran-PLA) NPs effectively increased the local drug concentration in tumor sites, minimized side effects, and significantly eliminated tumors, indicating the promising application of these NPs for cancer therapy. PMID:29527167

Folate-modified, curcumin and paclitaxel co-loaded PLA-TPGS nanoparticles: preparation, optimization and in vitro cytotoxicity assays

NASA Astrophysics Data System (ADS)

Doan Do, Hai; Le Thi, Hao; Huong Le Thi, Thu; Nguyen, Hoai Nam; Khanh Bui, Van; Nhung Hoang Thi, My; Thu Ha, Phuong

2018-06-01

Development of chemoresistance is a significant restriction on the success of cancer treatment. Combination chemotherapy and drug delivery nanosystem are two promising strategies to overcome this limitation. Administration of two or more anticancer drugs at the same time can promote synergistic effect and suppress drug resistance through distinct mechanisms of action. Drug delivery nanosystem, on the other hand, improves delivery, efficacy and safety of drugs, and also can escape from some mechanisms of drug resistance. In this study we prepared drug delivery nanosystems from copolymers of lactic acid (PLA) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). The nanosystems incorporated with folic acid as targeting agent were used to load curcumin (Cur) and paclitaxel (PTX) contemporaneously and denoted as (Cur  +  PTX)-PLA-TPGS-Fol. The results showed that (Cur  +  PTX)-PLA-TPGS-Fol nanoparticles has average size range of 100–200 nm depending on the ratio between PLA and TPGS. Loading efficacy of the two drugs was about 35%–83% with the highest encapsulation efficiency belonged to the system with the highest ratio of PLA. All of the prepared nanosystems with single drug or in combination exhibited strong cytotoxicity to cancer cells, but the combination was more effective in case of A549 cancer cell line. These results showed that our combination of Cur and PTX in our drug delivery nanosystem can be a promising candidate for cancer treatment.

Porous Silica-Supported Solid Lipid Particles for Enhanced Solubilization of Poorly Soluble Drugs.

PubMed

Yasmin, Rokhsana; Rao, Shasha; Bremmell, Kristen E; Prestidge, Clive A

2016-07-01

Low dissolution of drugs in the intestinal fluid can limit their effectiveness in oral therapies. Here, a novel porous silica-supported solid lipid system was developed to optimize the oral delivery of drugs with limited aqueous solubility. Using lovastatin (LOV) as the model poorly water-soluble drug, two porous silica-supported solid lipid systems (SSL-A and SSL-S) were fabricated from solid lipid (glyceryl monostearate, GMS) and nanoporous silica particles Aerosil 380 (silica-A) and Syloid 244FP (silica-S) via immersion/solvent evaporation. SSL particles demonstrated significantly higher rate and extent of lipolysis in comparison with the pure solid lipid, depending on the lipid loading levels and the morphology. The highest lipid digestion was observed when silica-S was loaded with 34% (w/w) solid lipid, and differential scanning calorimeter (DSC) analysis confirmed the encapsulation of up to 2% (w/w) non-crystalline LOV in this optimal SSL-S formulation. Drug dissolution under non-digesting intestinal conditions revealed a three- to sixfold increase in dissolution efficiencies when compared to the unformulated drug and a LOV-lipid suspension. Furthermore, the SSL-S provided superior drug solubilization under simulated intestinal digesting condition in comparison with the drug-lipid suspension and drug-loaded silica. Therefore, solid lipid and nanoporous silica provides a synergistic effect on optimizing the solubilization of poorly water-soluble compound and the solid lipid-based porous carrier system provides a promising delivery approach to overcome the oral delivery challenges of poorly water-soluble drugs.

Preparation of a novel lipid-core micelle using a low-energy emulsification method.

PubMed

Fritz, Hans F; Ortiz, Andrea C; Velaga, Sitaram P; Morales, Javier O

2018-04-16

High-energy methods for the manufacturing of nanomedicines are widely used; however, interest in low-energy methods is increasing due to their simplicity, better control over the process, and energy-saving characteristics during upscaling. Here, we developed a novel lipid-core micelle (LCM) as a nanocarrier to encapsulate a poorly water-soluble drug, nifedipine (NFD), by hot-melt emulsification, a low-energy method. LCMs are self-assembling colloidal particles composed of a hydrophobic core and a hydrophilic shell. Hybrid materials, such as Gelucire 44/14, are thus excellent candidates for their preparation. We characterized the obtained nanocarriers for their colloidal properties, drug loading and encapsulation efficiency, liquid state, stability, and drug release. The low-energy method hot-melt emulsification was successfully adapted for the manufacturing of small and narrowly dispersed LCMs. The obtained LCMs had a small average size of ~ 11 nm and a narrow polydispersity index (PDI) of 0.228. These nanocarriers were able to increase the amount of NFD dispersible in water more than 700-fold. Due to their sustained drug release profile and the PEGylation of Gelucire 44/14, these nanocarriers represent an excellent starting point for the development of drug delivery systems designed for long circulation times and passive targeting.

Fabrication of biodegradable micelles with sheddable poly(ethylene glycol) shells as the carrier of 7-ethyl-10-hydroxy-camptothecin.

PubMed

Guo, Qian; Luo, Ping; Luo, Yu; Du, Fang; Lu, Wei; Liu, Shiyuan; Huang, Jin; Yu, Jiahui

2012-12-01

Biodegradable micelles with sheddable poly(ethylene glycol) shells were fabricated based on poly(ethylene glycol)-block-poly(γ-benzyl L-glutamate) (mPEG-SS-PBLG) diblock copolymer and applied as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38) in order to enhance its solubility and stability in aqueous media. The diblock polymer was designed to have the hydrophilic PEG moiety and hydrophobic PBLG moiety linked by biodegradable disulfide bond, so in reducing environment the PEG shells can be detached. The polymer was able to form the micelles of nano-scale in aqueous media, suggesting their passive targeting potential to tumor tissue. Water-insoluble antitumor drug, SN-38, was easily encapsulated into mPEG-SS-PBLG nanomicelles by lyophilization method. When setting theoretical drug loading content at 10 wt%, the drug encapsulation efficiency (EE) was assayed as 73.5%. Owing to the disulfide bond in mPEG-SS-PBLG, intense release of SN-38 occurred in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition, however, micelles showed gradual release of SN-38 in the absence of DTT. Also, the mPEG-SS-PBLG micelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition. Compared with free SN-38, SN-38-loaded nanomicelles showed essentially decreased cytotoxicity against L929 cell line in 24h, bare mPEG-SS-PBLG nanomicelles showed almost non-toxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

Diclofenac Loaded Lipid Nanovesicles Prepared by Double Solvent Displacement for Skin Drug Delivery.

PubMed

Sala, M; Locher, F; Bonvallet, M; Agusti, G; Elaissari, A; Fessi, H

2017-09-01

Herein, we detail a promising strategy of nanovesicle preparation based on control of phospholipid self-assembly: the Double Solvent Displacement. A systematic study was conducted and diclofenac as drug model encapsulated. In vitro skin studies were carried out to identify better formulation for dermal/transdermal delivery. This method consists in two solvent displacements. The first one, made in a free water environment, has allowed triggering a phospholipid pre-organization. The second one, based on the diffusion into an aqueous phase has led to liposome formation. Homogeneous liposomes were obtained with a size close to 100 nm and a negative zeta potential around -40 mV. After incorporation of acid diclofenac, we obtained nanoliposomes with a size between 101 ± 45 and 133 ± 66 nm, a zeta potential between 34 ± 2 and 49 ± 3 mV, and the encapsulation efficiency (EE%) was between 58 ± 3 and 87 ± 5%. In vitro permeation studies showed that formulation with higher EE% dispayed the higher transdermal passage (18,4% of the applied dose) especially targeting dermis and beyond. Our results suggest that our diclofenac loaded lipid vesicles have significant potential as transdermal skin drug delivery system. Here, we produced cost effective lipid nanovesicles in a merely manner according to a process easily transposable to industrial scale. Graphical Abstract ᅟ.

Dual pH-sensitive supramolecular micelles from star-shaped PDMAEMA based on β-cyclodextrin for drug release.

PubMed

Zhou, Zaishuai; Guo, Feng; Wang, Nairong; Meng, Meng; Li, Guiying

2018-05-23

Star-shaped poly(2-(dimethylamino)ethyl methacrylate) based on β-cyclodextrin (β-CD-(PDMAEMA) 7 ) was synthesized by means of atomic transfer radical polymerization (ATRP). Dual pH-sensitive supramolecular micelles were formed from β-CD-(PDMAEMA) 7 and benzimidazole modified poly(ε-caprolactone) (BM-PCL) through the host-guest interactions between β-CD and benzimidazole. The supramolecular micelles have regular spherical structure with hydrophobic β-CD/BM-PCL as the core and pH-sensitive PDMAEMA as the shell. The hydrophobic PCL as well as the hydrophobic cavity of β-CD can efficiently encapsulate doxorubicin (DOX) with the drug-loading content and entrapment efficiency up to 40% and 86%. The drug release from micelles accelerated when the pH decreased from 7.0 to 2.0 and the temperature increased from 25 °C to 45 °C. MTT assay showed that drug loaded supramolecular micelles exhibited excellent anti-cancer activity than free DOX. These supramolecular micelles have promising potential applications as intelligent nanocarriers in drug delivery system. Copyright © 2018 Elsevier B.V. All rights reserved.

Preparation and in vitro characterization of retinoic acid-loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) micelles.

PubMed

Shakiba, Ebrahim; Khazaei, Saeedeh; Hajialyani, Marziyeh; Astinchap, Bandar; Fattahi, Ali

2017-12-01

In order to achieve the controlled release of all-trans-retinoic acid (ATRA), poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) copolymer with average molecular weight of 5.34 kDa was synthesized. The nanosized micelles were prepared from copolymer by nano-precipitation method. Critical association concentration (CAC) of micelles was measured by fluorimetry and results indicated low CAC value of micelles (1.9 × 10 -3 g/L). ATRA was encapsulated in the core of micelles using different ratios of drug to copolymer. In the case of 10% drug to polymer ratio, more than 80% of the drug was released within 3 days, whereas for ratio of 2% more than 90% of the drug was released within 3 h. The cytotoxic study performed by MTT assay showed that H1299 survival percent decreased significantly ( P ≤ 0.05) after exposure to drug-loaded micelles, while no proliferation inhibition effect was observed by either free ATRA or blank PCL-PEG-PCL micelles.

Chitosan-functionalised poly(2-hydroxyethyl methacrylate) core-shell microgels as drug delivery carriers: salicylic acid loading and release.

PubMed

Mahattanadul, Natshisa; Sunintaboon, Panya; Sirithip, Piyawan; Tuchinda, Patoomratana

2016-09-01

This work presents the evaluation of chitosan-functionalised poly(2-hydroxyethyl methacrylate) (CS/PHEMA) core-shell microgels as drug delivery carriers. CS/PHEMA microgels were prepared by emulsifier-free emulsion polymerisation with N,N '-methylenebisacrylamide (MBA) as a crosslinker. The study on drug loading, using salicylic acid (SA) as a model drug, was performed. The results showed that the encapsulation efficiency (EE) increased as drug-to-microgel ratio was increased. Higher EE can be achieved with the increase in degree of crosslinking, by increasing the amount of MBA from 0.01 g to 0.03 g. In addition, the highest EE (61.1%) was observed at pH 3. The highest release of SA (60%) was noticed at pH 2.4, while the lowest one (49.4%) was obtained at pH 7.4. Moreover, the highest release of SA was enhanced by the presence of 0.2 M NaCl. The pH- and ionic-sensitivity of CS/PHEMA could be useful as a sustained release delivery device, especially for oral delivery.

Development of chitosan oleate ionic micelles loaded with silver sulfadiazine to be associated with platelet lysate for application in wound healing.

PubMed

Dellera, Eleonora; Bonferoni, Maria Cristina; Sandri, Giuseppina; Rossi, Silvia; Ferrari, Franca; Del Fante, Claudia; Perotti, Cesare; Grisoli, Pietro; Caramella, Carla

2014-11-01

In the treatment of chronic wounds, topical application of anti-infective drugs such as silver sulfadiazine (AgSD) is of primary importance to avoid infections and accelerate wound repair. AgSD is used in burns and chronic wounds for its wide antibacterial spectrum, but presents limitations due to poor solubility and cytotoxicity. In the present work polymeric micelles obtained by self-assembling of chitosan ionically modified by interaction with oleic acid were developed as carriers for AgSD to overcome the drawbacks of the drug. The AgSD loaded micelles were intended to be associated in wound healing with platelet lysate (PL), a hemoderivative rich in growth factors. Unloaded micelles demonstrated good compatibility with both fibroblasts and PL. The relevance of chitosan concentration and of the ratio between chitosan and oleic acid to the drug loading and the particle size of nanoparticles was studied. A marked increase (up to 100 times with respect to saturated solution) of AgSD concentration in micelle dispersion was obtained. Moreover, the encapsulation reduced the cytotoxic effect of the drug towards fibroblasts and the drug incompatibility with PDGF-AB (platelet derived growth factor), chosen as representative of platelet growth factors. Copyright © 2014. Published by Elsevier B.V.

Chitosan microspheres as candidate plasmid vaccine carrier for oral immunisation of Japanese flounder (Paralichthys olivaceus).

PubMed

Tian, Jiyuan; Yu, Juan; Sun, Xiuqin

2008-12-15

Oral DNA-based immunotherapy is a new treatment option for fish immunisation in intensive culture. However, because of the existence of the nucleases and severe gastrointestinal conditions, DNA-based vaccines can be hydrolyzed or denatured. In our laboratory, a plasmid DNA (pDNA) containing major capsid protein (MCP) gene of lymphocystis disease virus (LCDV) was prepared, and then pDNA was encapsulated in chitosan microspheres through an emulsion-based methodology. The yield, loading percent and encapsulation efficiency of microspheres were 93.6%, 0.3% and 94.5%, respectively. Scanning electron microscopy (SEM) showed that pDNA-loaded microspheres yielded a spherical shape with smooth surfaces. The disproportion of super-coiled to open circle and linear pDNA suggested that high transfection efficiencies of pDNA in microspheres were retained. The cumulative release of pDNA showed that chitosan microspheres were resistant to degradation in simulated gastrointestinal tract environment. The release profile at PBS buffer (pH 7.4) displayed that pDNA-loaded chitosan microspheres had a release up to 42 days after intestinal imbibition. RT-PCR showed that RNA containing information of MCP gene existed in various tissues 10-90 days post-vaccination. SDS-PAGE and immunofluorescent images indicated that pDNA expressed MCP in tissues of fish 10-90 days after oral administration. In addition, indirect ELISA displayed that the immune responses of sera were positive (O.D.> or =0.3) from week 1 to week 16 for fish vaccinated with microspheres, in comparison with fish vaccinated with naked pDNA. Data obtained suggested that chitosan microspheres were promising carriers for oral pDNA vaccine. Because this encapsulation technique was easy to operate and immunisation efficacy of microspheres loaded with pDNA was significant, it had potential to be used in drug delivery applications.

Effect of a controlled-release drug delivery system made of oleanolic acid formulated into multivesicular liposomes on hepatocellular carcinoma in vitro and in vivo

PubMed Central

Luo, Yuling; Liu, Zhongbing; Zhang, Xiaoqin; Huang, Juan; Yu, Xin; Li, Jinwei; Xiong, Dan; Sun, Xiaoduan; Zhong, Zhirong

2016-01-01

The aim of the present study was to develop a novel dosage form of multivesicular liposomes for oleanolic acid (OA) to overcome its poor solubility, prolong therapeutic drug levels in the blood, and enhance the antitumor effect on hepatocellular carcinoma. OA-encapsulated multivesicular liposomes (OA-MVLs) were prepared by a double-emulsion method, and the formulation was optimized by the central composite design. The morphology, particle size, and drug-loading efficiency of OA-MVLs were investigated. Furthermore, OA-MVLs were also characterized both in vitro and in vivo. The results showed that OA-MVLs were spherical particles with an average particle size of 11.57 μm and an encapsulation efficiency of 82.3%±0.61%. OA-MVLs exhibited a sustained-release pattern in vitro, which was fitted to Ritger–Peppas equation. OA-MVLs inhibited the growth of human HepG2 cells which was confirmed by the MTT assay and fluorescence microscopy detection. The in vivo release of OA from OA-MVLs exhibited a sustained manner, indicating a longer circulation time compared to OA solution. The in vivo toxicity study indicated that medium-dose OA-MVLs exerted no toxic effect on the hosts. Importantly, OA-MVLs suppressed the growth of murine H22 hepatoma and prolonged the survival of tumor-bearing mice. In conclusion, the poorly soluble OA could be encapsulated into MVLs to form a novel controlled-release drug delivery system. The present study may hold promise for OA-MVLs as a new dosage form for sustained-release drug delivery in cancer therapy. PMID:27471381

Colloidal microgels in drug delivery applications

PubMed Central

Vinogradov, Serguei V.

2005-01-01

Colloidal microgels have recently received attention as environmentally responsive systems and now are increasingly used in applications as carriers for therapeutic drugs and diagnostic agents. Synthetic microgels consist of a crosslinked polymer network that provides a depot for loaded drugs, protection against environmental hazards and template for post-synthetic modification or vectorization of the drug carriers. The aim of this manuscript is to review recent attempts to develop new microgel formulations for oral drug delivery, to design metal-containing microgels for diagnostic and therapeutic applications, and to advance approaches including the systemic administration of microgels. Novel nanogel drug delivery systems developed in the authors’ laboratory are discussed in details including aspects of their synthesis, vectorization and recent applications for encapsulation of low molecular weight drugs or formulation of biological macromolecules. The findings reviewed here are encouraging for further development of the nanogels as intelligent drug carriers with such features as targeted delivery and triggered drug release. PMID:17168773

Enhanced gastric retention and drug release via development of novel floating microspheres based on Eudragit E100 and polycaprolactone: synthesis and in vitro evaluation

PubMed Central

Farooq, Umar; Khan, Samiullah; Nawaz, Shahid; Ranjha, Nazar Mohammad; Haider, Malik Salman; Khan, Muhammad Muzamil; Dar, Eshwa; Nawaz, Ahmad

2017-01-01

Abstract Eudragit E 100 and polycaprolactone (PCL) floating microspheres for enhanced gastric retention and drug release were successfully prepared by oil in water solvent evaporation method. Metronidazole benzoate, an anti-protozoal drug, was used as a model drug. Polyvinyl alcohol was used as an emulsifier. The prepared microspheres were observed for % recovery, % degree of hydration, % water uptake, % drug loading, % buoyancy and % drug release. The physico-chemical properties of the microspheres were studied by calculating encapsulation efficiency of microspheres and drug release kinetics. Drug release characteristics of microspheres were studied in simulated gastric fluid and simulated intestinal fluid i.e., at pH 1.2 and 7.4 respectively. Fourier transform infrared spectroscopy was used to reveal the chemical interaction between drug and polymers. Scanning electron microscopy was conducted to study the morphology of the synthesized microspheres. PMID:29491813

Iron oxide nanoparticles for magnetically-guided and magnetically-responsive drug delivery.

PubMed

Estelrich, Joan; Escribano, Elvira; Queralt, Josep; Busquets, Maria Antònia

2015-04-10

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release.

Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery

PubMed Central

Estelrich, Joan; Escribano, Elvira; Queralt, Josep; Busquets, Maria Antònia

2015-01-01

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release. PMID:25867479

Modulating drug release from gastric-floating microcapsules through spray-coating layers.

PubMed

Lee, Wei Li; Tan, Jun Wei Melvin; Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

2014-01-01

Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

Fabrication of redox-responsive magnetic protein microcapsules from hen egg white by the sonochemical method.

PubMed

Zhong, Shuangling; Cui, Xuejun; Tian, Fangyuan

2015-01-01

Redox-responsive magnetic protein microcapsules with Fe3O4 magnetic nanoparticles (MNPs) encapsulated inside have been obtained using a facile, cost-effective and fast sonochemical method from hen egg white proteins. Such prepared redox-responsive magnetic hen egg white protein microcapsules (MHEWPMCs) could be easily manipulated to do magnetic-guided targeting delivery. The synchronous loading of the hydrophobic dye Coumarin 6 as a model of drug into MHEWPMCs was readily achieved during the fabrication of MHEWPMCs by dissolving them into the oil phase before ultrasonication. TEM images indicated that Fe3O4 MNPs were encapsulated in MHEWPMCs. Confocal laser scanning microscopic images indicated that the dye was distributed evenly in the MHEWPMCs and no leakage of dye from the MHEWPMCs was observed due to the protection of protein shells. The MHEWPMCs are potential candidates as attractive carriers for drug targeting delivery and stimuli-responsive release due to their magnetic and redox responsiveness of the disulfide in the microcapsule shells.

Doxorubicin and Indocyanine Green Loaded Hybrid Bicelles for Fluorescence Imaging Guided Synergetic Chemo/Photothermal Therapy.

PubMed

Lin, Li; Liang, Xiaolong; Xu, Yunxue; Yang, Yongbo; Li, Xiaoda; Dai, Zhifei

2017-09-20

Hybrid bicelles have been demonstrated to have great potential for hydrophobic drug delivery. Herein, we report a near-infrared light-driven, temperature-sensitive hybrid bicelles co-encapsulating hydrophobic doxorubicin (DOX) and indocyanine green (ICG) (DOX/ICG@HBs). Encapsulation of ICG into the lipid bilayer membrane of DOX/ICG@HBs results in higher photostability than free ICG. DOX/ICG@HBs exhibited temperature-regulated drug release behavior and significant photothermal cytotoxicity. After tail vein injection, such discotic nanoparticles of DOX/ICG@HBs were found to accumulate selectively at the tumor site and act as an efficient probe to enhance fluorescence imaging greatly. The in vivo experiments showed that the DOX/ICG@HBs-mediated chemo- and photothermal combination therapy was more cytotoxic to tumor cells than the photothermal treatment or the chemotherapy alone due to the synergistic effect, reducing the occurrence of tumor metastasis. Therefore, DOX/ICG@HBs can act as a powerful nanotheranostic agent for chemo/photothermal therapy of cancer under the guidance of near-infrared fluorescence imaging.

Formation and characterization of β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated Fe3O4 nanoparticles for loading and releasing 5-Fluorouracil drug.

PubMed

Prabha, G; Raj, V

2016-05-01

In this work, β-cyclodextrin (β-CD) - polyethyleneglycol (PEG) - polyethyleneimine (PEI) coated iron oxide nanoparticles (Fe3O4-β-CD-PEG-PEI) were developed as drug carriers for drug delivery applications. The 5- Fluorouracil (5-FU) was chosen as model drug molecule. The developed nanoparticles (Fe3O4-β-CD-PEG-PEI) were characterized by various techniques such as Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). The average particles size range of 5-FU loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles were from 151 to 300nm and zeta potential value of nanoparticles were from -43mV to -20mV as measured using Malvern Zetasizer. Finally, encapsulation efficiency (EE), loading capacity (LC) and in-vitro drug release performance of 5-FU drug loaded Fe3O4-β-CD, Fe3O4-β-CD-PEG and Fe3O4-β-CD-PEG-PEI nanoparticles was evaluated by UV-vis spectroscopy. In-vitro cytotoxicity tests investigated by MTT assay indicate that 5-FU loaded Fe3O4-β-CD-PEG-PEI nanoparticles were toxic to cancer cells and non-toxic to normal cells. The in-vitro release behavior of 5-FU from drug (5-FU) loaded Fe3O4-β-CD-PEG-PEI composite at different pH values and temperature was studied. It was found that 5-FU was released faster in pH 6.8 than in the acidic mediums (pH 1.2), and the released quantity was higher. Therefore, the newly prepared Fe3O4-β-CD-PEG-PEI carrier exhibits a promising potential capability for anticancer drug delivery in tumor therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

High-oil-load encapsulation of medium-chain triglycerides and D-limonene mixture in modified starch by spray drying.

PubMed

Paramita, Vita; Furuta, Takeshi; Yoshii, Hidefumi

2012-02-01

Oil mixtures of medium-chain triglycerides (MCT) and D-limonene in mixing ratios from 10 to 100 wt% were encapsulated in modified starch (wall material) by spray drying to produce oil-rich powders. The oil load (mass ratio of oil mixture to wall material) of the infeed emulsion markedly influenced the properties of the infeed liquid and the characteristics of the resulting powder. The viscosity of the infeed liquid and the particle size of the powder exponentially decreased with increasing oil load, while the emulsion droplet size in the infeed liquid increased. In addition, retention of D-limonene during spray drying also decreased markedly with increasing oil load. Irrespective of the different oil loads and concentrations of the wall material, D-limonene retention was well correlated with the emulsion droplet diameter of the infeed liquid. The encapsulation efficiency of the oil mixture exhibited a maximum value (almost 100%) at an oil load between 0.5 and 1.0, before decreasing at higher oil loads. At an oil load of 2.0, the encapsulation efficiency of D-limonene was reduced to almost zero, while around 40% of the initial MCT was encapsulated in the powder. The increase in oil load also led to increased amounts of surface oil of MCT and D-limonene in the resulting powder due to the increasing emulsion droplet diameter of the infeed liquids. This study proposes the microencapsulation of medium-chain triglycerides under high-oil-load conditions by spray drying. The powders prepared by this process provide significant benefits in terms of rapid energy conversion after consumption without accumulation in the body. Important quality factors of the powder products such as the encapsulation efficiency and the amount of surface oil were examined to understand the optimum process conditions for spray drying. © 2012 Institute of Food Technologists®

Fluorogenic pH-sensitive polydiacetylene (PDA) liposomes as a drug carrier.

PubMed

Won, Sang Ho; Lee, Jong Uk; Sim, Sang Jun

2013-06-01

A crucial issue for current liposomal carriers in clinical applications is the sustained-release property of the encapsulated drugs. We have developed novel fluorogenic pH-sensitive polymerized liposomes composed of polydiacetylene (PDA) lipids and other types of lipids. Unilamellar liposomes containing 10,12-pentacosadiynoic acid (PCDA), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and N-palmitoyl homocysteine (PHC) were loaded with ampicillin. These liposomes fused to each other rapidly when the medium pH was lowered from 7 to 4. The polymerized liposomes were characterized in terms of particle size distribution. The liposome size increased approximately 20-fold from 110.0 +/- 19.3 nm to 2046.7 +/- 487.4 nm as the pH was lowered. Cross-linking of the diacetylene lipids prevents drug leakage and the encapsulated drug can be instantaneously released at acidic pH condition. The ampicillin was nearly completely released (74.4 +/- 3.9%) from liposomes within 4 h under acidic pH conditions and the released amounts of ampicillin were analyzed by HPLC. Finally, the therapeutic effect was observed by the appearance of plaques on a lawn of E. coli, and fluorescent images of the PDA liposomes were taken from the plaques for drug release monitoring. As a result, this research demonstrates that such novel pH-sensitive polymerized liposomes have great prospects as a drug carrier.

One-step formation of lipid-polyacrylic acid-calcium carbonate nanoparticles for co-delivery of doxorubicin and curcumin.

PubMed

Peng, Jianqing; Fumoto, Shintaro; Miyamoto, Hirotaka; Chen, Yi; Kuroda, Naotaka; Nishida, Koyo

2017-09-01

A doxorubicin (Dox) and curcumin (Cur) combination treatment regimen has been widely studied in pre-clinical research. However, the nanoparticles developed for this combination therapy require a consecutive drug loading process because of the different water-solubility of these drugs. This study provides a strategy for the "one-step" formation of nanoparticles encapsulating both Dox and Cur. We took advantage of polyacrylic acid (PAA) and calcium carbonate (CaCO 3 ) to realise a high drug entrapment efficiency (EE) and pH-sensitive drug release using a simplified preparation method. Optimisation of lipid ratios and concentrations of CaCO 3 was conducted. Under optimal conditions, the mean diameter of PEGylated lipid/PAA/CaCO 3 nanoparticles with encapsulated Cur and Dox (LPCCD) was less than 100 nm. An obvious pH-sensitive release of both drugs was observed, with different Dox and Cur release rates. Successful co-delivery of Cur and Dox was achieved via LPCCD on HepG2 cells. LPCCD altered the bio-distribution of Dox and Cur in vivo and decreased Dox-induced cardiotoxicity. The current investigation has developed an efficient ternary system for co-delivery of Dox and Cur to tumours, using a "one-step" formation resulting in nanoparticles possessing remarkable pH-sensitive drug release behaviour, which may be valuable for further clinical studies and eventual clinical application.

Enhanced stability and dermal delivery of hydroquinone using solid lipid nanoparticles.

PubMed

Ghanbarzadeh, Saeed; Hariri, Reza; Kouhsoltani, Maryam; Shokri, Javad; Javadzadeh, Yousef; Hamishehkar, Hamed

2015-12-01

Hydroquinone (HQ), a well-known anti-hyperpigmentation agent suffers from (a) instability due to rapid oxidation, (b) insufficient skin penetration because of hydrophilic structure, and (c) severe side effects as a results of systemic absorption. This study aimed to load HQ into solid lipid nanoparticles (SLNs) to overcome the mentioned drawbacks for the efficient treatment of hyperpigmentation. The optimized SLN formulation was prepared by hot melt homogenization method and fully characterized by various techniques. The ability of SLNs in dermal delivery of HQ was assessed through the excised rat skin. The optimized HQ-loaded SLNs (particle size of 86 nm, encapsulation efficiency% of 89.5% and loading capacity% of 11.2%) exhibited a good physicochemical stability during a period of five months. XRD and DSC results showed that HQ was dispersed in an amorphous state, confirming uniform drug dispersion in the SLNs structure and embedment of drug in the solid lipid matrix. In vitro penetration studies showed almost 3 times higher drug accumulation in the skin and 6.5 times lower drug entrance to receiving compartment of Franz diffusion cell from HQ-loaded SLN hydrogel compared with HQ Carbopol made hydrogel. These results indicated the better HQ localization in the skin and its lower systemic absorption. It was concluded that SLN is a promising colloidal drug carrier for topical administration of HQ in the treatment of hyperpigmentation due to suitable HQ loading value in spite of its hydrophilic structure, high stability against oxidation and appropriate skin penetration along with the low systemic absorption. Copyright © 2015 Elsevier B.V. All rights reserved.

Surfactant protein-A nanobody-conjugated liposomes loaded with methylprednisolone increase lung-targeting specificity and therapeutic effect for acute lung injury.

PubMed

Li, Nan; Weng, Dong; Wang, Shan-Mei; Zhang, Yuan; Chen, Shan-Shan; Yin, Zhao-Fang; Zhai, Jiali; Scoble, Judy; Williams, Charlotte C; Chen, Tao; Qiu, Hui; Wu, Qin; Zhao, Meng-Meng; Lu, Li-Qin; Mulet, Xavier; Li, Hui-Ping

2017-11-01

The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb. MPS-NSSLs-SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS-NSSLs-SPANb to the lung. Treatment with MPS-NSSLs-SPANb reduced the levels of TNF-α, IL-8, and TGF-β1 in rat bronchoalveolar lavage fluid and the expression of NK-κB in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.

Oral delivery of exenatide via microspheres prepared by cross-linking of alginate and hyaluronate.

PubMed

Zhang, Baojie; He, Dongyang; Fan, Yu; Liu, Nan; Chen, Yijun

2014-01-01

Exenatide is an FDA-approved glucose-lowering peptide drug for the treatment of type 2 diabetes by subcutaneous injection. To address the issues on the inconvenience for patient use and the difficulty of oral administration of peptide drugs, chemical cross-linking of two pH-responsive biomaterials, alginate and hyaluronate, was carried out to prepare a new material for the encapsulation of exenatide as a form of microspheres. The exenatide-loaded microspheres exhibited spherical structures with excellent loading and release behaviors in the simulated gastrointestinal tract environments. After oral administration of the microspheres in db/db mice, maximum plasma concentration of exenatide appeared at 4 hours, and blood glucose was effectively reduced to a normal level within 2 hours and maintained for another 4 hours. The bioavailability of the exenatide-loaded microspheres, relative to subcutaneous injection of exenatide, reached 10.2%. Collectively, the present study demonstrated the feasibility of orally delivering exenatide with the new cross-linked biomaterial and formulation, and showed therapeutic potential for clinical applications.

Oral Delivery of Exenatide via Microspheres Prepared by Cross-Linking of Alginate and Hyaluronate

PubMed Central

Zhang, Baojie; He, Dongyang; Fan, Yu; Liu, Nan; Chen, Yijun

2014-01-01

Exenatide is an FDA-approved glucose-lowering peptide drug for the treatment of type 2 diabetes by subcutaneous injection. To address the issues on the inconvenience for patient use and the difficulty of oral administration of peptide drugs, chemical cross-linking of two pH-responsive biomaterials, alginate and hyaluronate, was carried out to prepare a new material for the encapsulation of exenatide as a form of microspheres. The exenatide-loaded microspheres exhibited spherical structures with excellent loading and release behaviors in the simulated gastrointestinal tract environments. After oral administration of the microspheres in db/db mice, maximum plasma concentration of exenatide appeared at 4 hours, and blood glucose was effectively reduced to a normal level within 2 hours and maintained for another 4 hours. The bioavailability of the exenatide-loaded microspheres, relative to subcutaneous injection of exenatide, reached 10.2%. Collectively, the present study demonstrated the feasibility of orally delivering exenatide with the new cross-linked biomaterial and formulation, and showed therapeutic potential for clinical applications. PMID:24465870

Evaluation of photodynamic activity, photostability and in vitro drug release of zinc phthalocyanine-loaded nanocapsules.

PubMed

de Souza, Thiane Deprá; Ziembowicz, Francieli Isa; Müller, Debora Friedrich; Lauermann, Sâmera Cristina; Kloster, Carmen Luisa; Santos, Roberto Christ Vianna; Lopes, Leonardo Quintana Soares; Ourique, Aline Ferreira; Machado, Giovanna; Villetti, Marcos Antonio

2016-02-15

Nanocapsule formulations containing zinc phthalocyanine (ZnPc) were investigated as drug delivery systems for use in photodynamic therapy (PDT). ZnPc loaded chitosan, PCL, and PCL coated with chitosan nanocapsules were prepared and characterized by means of their physicochemical properties, photodynamic activity, photostability and drug release profile. All formulations presented nanometric hydrodynamic radius, around 100 nm, low polydispersity index (0.08-0.24), slightly negative zeta potential for PCL nanoparticles and positive zeta potential for suspension containing chitosan. Encapsulation efficiencies were higher than 99%. The capacity of ZnPc loaded nanocapsules to produce cytotoxic singlet oxygen ((1)O2) by irradiation with red laser was monitored using 1.3-diphenylisobenzofuran as a probe. The singlet oxygen quantum yields (ΦΔ) for ZnPc loaded chitosan nanocapsules were high and similar to that of the standard (ZnPc in DMSO), displaying excellent ability to generate (1)O2. The photosensitizer loaded nanocapsules are photostable in the timescale usually utilized in PDT and only a small photobleaching event was observed when a light dose of 610J/cm(2) was applied. The in vitro drug release studies of ZnPc from all nanocapsules demonstrated a sustained release profile controlled by diffusion, without burst effect. The nature of the polymer and the core type of the nanocapsules regulated ZnPc release. Thus, the nanocapsules developed in this work are a promising strategy to be employed in PDT. Copyright © 2015. Published by Elsevier B.V.

Synthesis, characterization and drug loading property of Monomethoxy-Poly(ethylene glycol)-Poly(ε-caprolactone)-Poly(D,L-lactide) (MPEG-PCLA) copolymers

PubMed Central

Chu, BingYang; Zhang, Lan; Qu, Ying; Chen, XiaoXin; Peng, JinRong; Huang, YiXing; Qian, ZhiYong

2016-01-01

Amphiphilic block copolymers have attracted a great deal of attention in drug delivery systems. In this work, a series of monomethoxy-poly (ethylene glycol)-poly (ε-caprolactone-co-D,L-lactide) (MPEG-PCLA) copolymers with variable composition of poly (ε-caprolactone) (PCL) and poly (D,L-lactide) (PDLLA) were prepared via ring-opening copolymerization of ε-CL and D,L-LA in the presence of MPEG and stannous octoate. The structure and molecular weight were characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). The crystallinity, hydrophilicity, thermal stability and hydrolytic degradation behavior were investigated in detail, respectively. The results showed that the prepared amphiphilic MPEG-PCLA copolymers have adjustable properties by altering the composition of PCLA, which make it convenient for clinical applications. Besides, the drug loading properties were also studied. Docetaxel (DTX) could be entrapped in MPEG-PCLA micelles with high loading capacity and encapsulation efficiency. And all lyophilized DTX-loaded MPEG-PCLA micelles except MPEG-PCL micelles were readily re-dissolved in normal saline at 25 °C. In addition, DTX-loaded MPEG-PCLA micelles showed a slightly enhanced antitumor activity compared with free DTX. Furthermore, DTX micelles exhibited a slower and sustained release behavior in vitro, and higher DTX concentration and longer retention time in vivo. The results suggested that the MPEG-PCLA copolymer with the adjustable ratio of PCL to PDLLA may be a promising drug delivery carrier for DTX. PMID:27677842

pH-responsive polymer-drug conjugates as multifunctional micelles for cancer-drug delivery

NASA Astrophysics Data System (ADS)

Kang, Yang; Ha, Wei; Liu, Ying-Qian; Ma, Yuan; Fan, Min-Min; Ding, Li-Sheng; Zhang, Sheng; Li, Bang-Jing

2014-08-01

We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)-4β-aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4β-aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles simultaneously served as an anticancer drug conjugate and as drug carriers. As a drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei of the tumor cells and led to much more cytotoxic effects to A549, Hela, and HepG2 cancer cells than the parent NPOD. The half maximal inhibitory concentration (IC50) of mPEG-NPOD-I was about one order magnitude lower than that of the NPOD. In vivo, mPEG-NPOD-I reduced the size of the tumors significantly, and the biodistribution studies indicated that this drug conjugate could selectively accumulate in tumor tissues. As drug carriers, the mPEG-NPOD-I micelles encapsulated hydrophobic PTX with drug-loading efficiencies of 57% and drug-loading content of 16%. The loaded PTX also showed pH-triggered fast release behavior, and good additive cytotoxicity effect was observed for the PEG-NPOD-I/PTX. We are convinced that these multifunctional drug conjugate micelles have tremendous potential for targeted cancer therapy.

pH-responsive polymer-drug conjugates as multifunctional micelles for cancer-drug delivery.

PubMed

Kang, Yang; Ha, Wei; Liu, Ying-Qian; Ma, Yuan; Fan, Min-Min; Ding, Li-Sheng; Zhang, Sheng; Li, Bang-Jing

2014-08-22

We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)-4β-aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4β-aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles simultaneously served as an anticancer drug conjugate and as drug carriers. As a drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei of the tumor cells and led to much more cytotoxic effects to A549, Hela, and HepG2 cancer cells than the parent NPOD. The half maximal inhibitory concentration (IC₅₀) of mPEG-NPOD-I was about one order magnitude lower than that of the NPOD. In vivo, mPEG-NPOD-I reduced the size of the tumors significantly, and the biodistribution studies indicated that this drug conjugate could selectively accumulate in tumor tissues. As drug carriers, the mPEG-NPOD-I micelles encapsulated hydrophobic PTX with drug-loading efficiencies of 57% and drug-loading content of 16%. The loaded PTX also showed pH-triggered fast release behavior, and good additive cytotoxicity effect was observed for the PEG-NPOD-I/PTX. We are convinced that these multifunctional drug conjugate micelles have tremendous potential for targeted cancer therapy.

Ultrasound enhanced release of therapeutics from drug-releasing implants based on titania nanotube arrays.

PubMed

Aw, Moom Sinn; Losic, Dusan

2013-02-25

A non-invasive and external stimulus-driven local drug delivery system (DDS) based on titania nanotube (TNT) arrays loaded with drug encapsulated polymeric micelles as drug carriers and ultrasound generator is described. Ultrasound waves (USW) generated by a pulsating sonication probe (Sonotrode) in phosphate buffered saline (PBS) at pH 7.2 as the medium for transmitting pressure waves, were used to release drug-loaded nano-carriers from the TNT arrays. It was demonstrated that a very rapid release in pulsatile mode can be achieved, controlled by several parameters on the ultrasonic generator. This includes pulse length, time, amplitude and power intensity. By optimization of these parameters, an immediate drug-micelles release of 100% that spans a desirable time of 5-50 min was achieved. It was shown that stimulated release can be generated and reproduced at any time throughout the TNT-Ti implant life, suggesting considerable potential of this approach as a feasible and tunable ultrasound-mediated drug delivery system in situ via drug-releasing implants. It is expected that this concept can be translated from an in vitro to in vivo regime for therapeutic applications using drug-releasing implants in orthopedic and coronary stents. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Formulation Optimization of Human Insulin Loaded Microspheres for Controlled Oral Delivery Using Response Surface Methodology.

PubMed

Agrawal, Gauravkuma; Wakte, Pravin; Shelke, Santosh

2017-01-01

The objectives of the present investigation were to prepare recombinant human insulin entrapped Eudragit-S100 microspheres containing protease inhibitors and to precisely analyze the outcome of different formulation variables on the microspheres properties using a response surface methodology to develop an optimized formulation with desirable features. A central composite design was employed to produce microspheres of therapeutic protein by w/o/w multiple emulsion solvent evaporation technique using Eudragit S-100 as coating material and polyvinyl alcohol as a stabilizer. The effect of formulation variables (independent variables) that is levels of Eudragit S-100 (X1), therapeutic protein (X2), volumes of inner aqueous phase (X3) and external aqueous phase (X4) on dependant variables, that are encapsulation efficiency (Y1), drug release at pH 1.2 after 2 h (Y2) and drug release at pH 7.4 after of 2 h (Y3) were evaluated. The significant terms in the mathematical models were generated for each response parameter using multiple linear regression analysis and analysis of variance. All the formulation variables except the volume of external aqueous phase (X4) exerted a significant effect (P <0.05) on drug encapsulation efficiency (Y1) whereas first two variables, namely the levels of Eudragit S-100 (X1) and therapeutic protein (X2) materialized as the determining factors which significantly influenced drug release at pH 1.2 after 2 h (Y2) and drug release at pH 7.4 after of 2 h (Y3). The formulation was numerically optimized by framing the constraints on the dependent and independent variables using the desirability approach. The experimental values for Y1 and Y2 of optimized formulation were found to be 77.65% and 3.64%, respectively which were quite closer to results suggested by software. The results recorded indicate that the recombinant human insulin loaded Eudragit S-100 microspheres containing aprotinin have the benefits of higher loading efficiency, pH responsive and prolonged release characteristics, which may help to carry insulin to the optimum site of absorption. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

PEGylated Silk Nanoparticles for Anticancer Drug Delivery.

PubMed

Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew J; Seib, F Philipp

2015-11-09

Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of "stealth" design principals is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential -56 ± 5.6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using clinically established and emerging anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation efficiency (>93%) and a pH-dependent release over 14 days. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines to human breast cancer cells. In conclusion, these results, taken together with prior silk nanoparticle data, support a viable future for silk-based nanomedicines.

Amphiphilic polymeric micelles as the nanocarrier for peroral delivery of poorly soluble anticancer drugs.

PubMed

Tian, Ye; Mao, Shirui

2012-06-01

Many amphiphilic copolymers have recently been synthesized as novel promising micellar carriers for the delivery of poorly water-soluble anticancer drugs. Studies on the formulation and oral delivery of such micelles have demonstrated their efficacy in enhancing drug uptake and absorption, and exhibit prolonged circulation time in vitro and in vivo. In this review, literature on hydrophobic modifications of several hydrophilic polymers, including polyethylene glycol, chitosan, hyaluronic acid, pluronic and tocopheryl polyethylene glycol succinate, is summarized. Parameters influencing the properties of polymeric micelles for oral chemotherapy are discussed and strategies to overcome main barriers for polymeric micelles peroral absorption are proposed. During the design of polymeric micelles for peroral chemotherapy, selecting or synthesizing copolymers with good compatibility with the drug is an effective strategy to increase drug loading and encapsulation efficiency. Stability of the micelles can be improved in different ways. It is recommended to take permeability, mucoadhesion, sustained release, and P-glycoprotein inhibition into consideration during copolymer preparation or to consider adding some excipients in the formulation. Furthermore, both the copolymer structure and drug loading methods should be controlled in order to get micelles with appropriate particle size for better absorption.

All-atomistic molecular dynamics (AA-MD) studies and pharmacokinetic performance of PAMAM-dendrimer-furosemide delivery systems.

PubMed

Otto, Daniel P; de Villiers, Melgardt M

2018-06-13

Improvement of problematic dissolution and solubility properties of a model drug, furosemide, was investigated for poly(amidoamine) (PAMAM) dendrimer complexes of the drug. Full and half generation dendrimers with amino and ester terminals respectively, were studied. In vitro release performance of these complexes was investigated at drug loads ranging 5-60% using simulated gastric fluids. Full generation dendrimers accommodated higher drug loads, outperformed half-generation complexes, and free drug. Pharmacokinetic studies in rats indicated that the dendrimer complexes markedly improved in the bioavailability of the drug compared to the unformulated drug. The G3.0-PAMAM dendrimer complex showed a two-fold increase in C max and a 1.75-fold increase in AUC over the free drug. Additionally, T max was shortened from approximately 25 to 20 min. One of the first all-atomistic molecular dynamics (AA-MD) simulation studies was performed to evaluate low-generation dendrimer-drug complexes as well as its pharmacokinetic performance. AA-MD provided insight into the intermolecular interactions that take place between the dendrimer and drug. It is suggested that the dendrimer not only encapsulates the drug, but can also orientate the drug in stabilized dispersion to prevent drug clustering which could impact release and bioavailability negatively. AA-MD can be a useful tool to develop dendrimer-based drug delivery systems. Copyright © 2018. Published by Elsevier B.V.

Tailored design of multifunctional and programmable pH-responsive self-assembling polypeptides as drug delivery nanocarrier for cancer therapy.

PubMed

Wang, Tzu-Wei; Yeh, Chia-Wei; Kuan, Chen-Hsiang; Wang, Li-Wen; Chen, Liang-Hsin; Wu, Hsi-Chin; Sun, Jui-Shen

2017-08-01

Breast cancer has become the second leading cause of cancer-related mortality in female wherein more than 90% of breast cancer-related death results from cancer metastasis to distant organs at advanced stage. The purpose of this study is to develop biodegradable nanoparticles composed of natural polypeptides and calcium phosphate (CaP) with sequential pH-responsivity to tumor microenvironments for active targeted drug delivery. Two different amphiphilic copolymers, poly(ethylene glycol) 3400 -aconityl linkage-poly(l-glutamic acid) 15 -poly(l-histidine) 10 -poly(l-leucine) 10 and LyP1-poly(ethylene glycol) 1100 -poly(l-glutamic acid) 15 -poly(l-histidine) 10 -poly(l-leucine) 10 , were exploited to self-assemble into micelles in aqueous phase. The bio-stable nanoparticles provide three distinct functional domains: the anionic PGlu shell for CaP mineralization, the protonation of PHis segment for facilitating anticancer drug release at target site, and the hydrophobic core of PLeu for encapsulation of anticancer drugs. Furthermore, the hydrated PEG outer corona is used for prolonging circulation time, while the active targeting ligand, LyP-1, is served to bind to breast cancer cells and lymphatic endothelial cells in tumor for inhibiting metastasis. Mineralized DOX-loaded nanoparticles (M-DOX NPs) efficiently prevent the drug leakage at physiological pH value and facilitate the encapsulated drug release at acidic condition when compared to DOX-loaded nanoparticles (DOX NPs). M-DOX NPs with LyP-1 targeting ligand effectively accumulated in MDA-MB-231 breast cancer cells. The inhibition effect on cell proliferation also enhances with time, illustrating the prominent anti-tumor efficacy. Moreover, the in vitro metastatic inhibition model shows the profound inhibition effect of inhibitory nanoparticles. In brief, this self-assembling peptide-based drug delivery nanocarrier with multifunctionality and programmable pH-sensitivity is of great promise and potential for anti-cancer therapy. This tailored-design polypeptide-based nanoparticles with self-assembling and programmable stimulus-responsive properties enable to 1) have stable pH in physiological value with a low level of drug loss and effectively release the encapsulated drug with pH variations according to the tumor microenvironment, 2) enhance targeting ability to hard-to-treat breast cancer cells and activate endothelial cells (tumor region), 3) significantly inhibit the growth and prevent from malignant metastasis of cancer cells in consonance with promising anti-tumor efficacy, and 4) make tumors stick to localized position so that these confined solid tumors can be more accessible by different treatment modalities. This work contributes to designing a programmable pH-responsive drug delivery system based on the tailor-designed polypeptides. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Neuroprotective effect of curcumin-loaded lactoferrin nano particles against rotenone induced neurotoxicity.

PubMed

Bollimpelli, V Satish; Kumar, Prashant; Kumari, Sonali; Kondapi, Anand K

2016-05-01

Curcumin is known to have neuroprotective role and possess antioxidant, anti-inflammatory activities. Rotenone, a flavonoid induced neurotoxicity in dopaminergic cells is being widely studied in Parkinson's Disease (PD) research. In the present study, curcumin loaded lactoferrin nano particles prepared by sol-oil chemistry were used to protect dopaminergic cell line SK-N-SH against rotenone induced neurotoxicity. These curcumin loaded nano particles were of 43-60 nm diameter size and around 100 nm hydrodynamic size as assessed by transmission electron microscopy, atomic force microscopy and dynamic light scattering analysis respectively. The encapsulation efficiency was 61.3% ± 2.4%. Cellular uptake of curcumin through these nano particles was confirmed by confocal imaging and spectrofluorimetric analysis. The curcumin loaded lactoferrin nanoparticles showed greater intracellular drug uptake, sustained retention and greater neuroprotection than soluble counterpart. Neuroprotective activity was characterized through viability assays and by estimating ROS levels. Furthermore rotenone induced PD like features were characterized by decrease in tyrosine hydroxylase expression and increase in α-synuclein expression. Taken together curcumin loaded lactoferrin nanoparticles could be a promising drug delivery strategy against neurotoxicity in dopaminergic neurons. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diffusion-Limited Cargo Loading of an Engineered Protein Container.

PubMed

Zschoche, Reinhard; Hilvert, Donald

2015-12-30

The engineered bacterial nanocompartment AaLS-13 is a promising artificial encapsulation system that exploits electrostatic interactions for cargo loading. In order to study its ability to take up and retain guests, a pair of fluorescent proteins was developed which allows spectroscopic determination of the extent of encapsulation by Förster resonance energy transfer (FRET). The encapsulation process is generally complete within a second, suggesting low energetic barriers for proteins to cross the capsid shell. Formation of intermediate aggregates upon mixing host and guest in vitro complicates capsid loading at low ionic strength, but can be sidestepped by increasing salt concentrations or diluting the components. Encapsulation of guests is completely reversible, and the position of the equilibrium is easily tuned by varying the ionic strength. These results, which challenge the notion that AaLS-13 is a continuous rigid shell, provide valuable information about cargo loading that will guide ongoing efforts to engineer functional host-guest complexes. Moreover, it should be possible to adapt the protein FRET pair described in this report to characterize functional capsid-cargo complexes generated by other encapsulation systems.

Method for loading lipid like vesicles with drugs of other chemicals

DOEpatents

Mehlhorn, R.J.

1998-06-09

A method for accumulating drugs or other chemicals within synthetic, lipid-like vesicles by means of a pH gradient imposed on the vesicles just prior to use is described. The method is suited for accumulating molecules with basic or acid moieties which are permeable to the vesicles membranes in their uncharged form and for molecules that contain charge moieties that are hydrophobic ions and can therefore cross the vesicle membranes in their charged form. The method is advantageous over prior art methods for encapsulating biologically active materials within vesicles in that is achieves very high degrees of loading with simple procedures that are economical and require little technical expertise, furthermore kits which can be stored for prolonged periods prior to use without impairment of the capacity to achieve drug accumulation are described. A related application of the method consists of using this technology to detoxify animals that have been exposed to poisons with basic, weak acid or hydrophobic charge groups within their molecular structures. 2 figs.

Method for loading lipid like vesicles with drugs of other chemicals

DOEpatents

Mehlhorn, Rolf Joachim

1998-01-01

A method for accumulating drugs or other chemicals within synthetic, lipid-like vesicles by means of a pH gradient imposed on the vesicles just prior to use is described. The method is suited for accumulating molecules with basic or acid moieties which are permeable to the vesicles membranes in their uncharged form and for molecules that contain charge moieties that are hydrophobic ions and can therefore cross the vesicle membranes in their charged form. The method is advantageous over prior art methods for encapsulating biologically active materials within vesicles in that is achieves very high degrees of loading with simple procedures that are economical and require little technical expertise, furthermore kits which can be stored for prolonged periods prior to use without impairment of the capacity to achieve drug accumulation are described. A related application of the method consists of using this technology to detoxify animals that have been exposed to poisons with basic, weak acid or hydrophobic charge groups within their molecular structures.

Albumin microspheres as an ocular delivery system for pilocarpine nitrate.

PubMed

Rathod, Sudha; Deshpande, S G

2008-01-01

Pilocarpine nitrate loaded egg albumin microspheres were prepared by thermal denaturation process in the size range of 1-12 mum. A series of batches were prepared to study factors, which may affect the size and entrapment efficiency of drug in microspheres and optimized the process. Drug loaded microspheres so obtained were evaluated for their size, entrapment efficiency, release rate and biological response. Electron photomicrographs were taken (8000X) to study the morphological characteristics of microspheres. The entrapment and encapsulation of pilocarpine after process optimization was found to be 82.63% and 62.5% respectively. In vitro dissolution rate studies revealed that the release of drug from the microspheres followed spherical matrix mechanism. Biological response of microspheric suspension was measured by reduction in intraocular pressure in albino rabbit eyes and compared with marketed eye drops. Various pharmacokinetic parameters viz. onset of action, duration of action, Tmax and AUC were studied. A measurable difference was found in the mean miotic response, duration and AUC of pilocarpine nitrate microspheric suspension.

Stratum corneum lipid liposome-encapsulated panomycocin: preparation, characterization, and the determination of antimycotic efficacy against Candida spp. isolated from patients with vulvovaginitis in an in vitro human vaginal epithelium tissue model.

PubMed

İzgü, Fatih; Bayram, Günce; Tosun, Kübra; İzgü, Demet

2017-01-01

In this study, a liposomal lyophilized powder formulation of panomycocin was developed for therapeutic purposes against vulvovaginal candidiasis which affects 80% of women worldwide. Panomycocin is a potent antimycotic protein secreted by the yeast Wickerhamomyces anomalus NCYC 434. This study involved the preparation of panomycocin-loaded stratum corneum lipid liposomes (SCLLs), characterization of the SCLLs, and determination of antimycotic efficacy of the formulation against Candida albicans and Candida glabrata clinical vaginal isolates in a human vaginal epithelium tissue model. The encapsulation and loading efficiencies of SCLLs were 73% and 76.8%, respectively. In transmission electron microscopy images, the SCLLs appeared in the submicron size range. Dynamic light scattering analyses showed that the SCLLs had uniform size distribution. Zeta potential measurements revealed stable and positively charged SCLLs. In Fourier transform infrared spectroscopy analyses, no irreversible interactions between the encapsulated panomycocin and the SCLLs were detected. The SCLLs retained >98% of encapsulated panomycocin in aqueous solution up to 12 hours. The formulation was fungicidal at the same minimum fungicidal concentration values for non-formulated pure panomycocin when tested on an in vitro model of vaginal candidiasis. This is the first study in which SCLLs and a protein as an active ingredient have been utilized together in a formulation. The results obtained in this study led us to conduct further preclinical trials of this formulation for the development of an effective topical anti-candidal drug with improved safety.

Stratum corneum lipid liposome-encapsulated panomycocin: preparation, characterization, and the determination of antimycotic efficacy against Candida spp. isolated from patients with vulvovaginitis in an in vitro human vaginal epithelium tissue model

PubMed Central

İzgü, Fatih; Bayram, Günce; Tosun, Kübra; İzgü, Demet

2017-01-01

In this study, a liposomal lyophilized powder formulation of panomycocin was developed for therapeutic purposes against vulvovaginal candidiasis which affects 80% of women worldwide. Panomycocin is a potent antimycotic protein secreted by the yeast Wickerhamomyces anomalus NCYC 434. This study involved the preparation of panomycocin-loaded stratum corneum lipid liposomes (SCLLs), characterization of the SCLLs, and determination of antimycotic efficacy of the formulation against Candida albicans and Candida glabrata clinical vaginal isolates in a human vaginal epithelium tissue model. The encapsulation and loading efficiencies of SCLLs were 73% and 76.8%, respectively. In transmission electron microscopy images, the SCLLs appeared in the submicron size range. Dynamic light scattering analyses showed that the SCLLs had uniform size distribution. Zeta potential measurements revealed stable and positively charged SCLLs. In Fourier transform infrared spectroscopy analyses, no irreversible interactions between the encapsulated panomycocin and the SCLLs were detected. The SCLLs retained >98% of encapsulated panomycocin in aqueous solution up to 12 hours. The formulation was fungicidal at the same minimum fungicidal concentration values for non-formulated pure panomycocin when tested on an in vitro model of vaginal candidiasis. This is the first study in which SCLLs and a protein as an active ingredient have been utilized together in a formulation. The results obtained in this study led us to conduct further preclinical trials of this formulation for the development of an effective topical anti-candidal drug with improved safety. PMID:28831255

Nanogel-based natural polymers as smart carriers for the controlled delivery of Timolol Maleate through the cornea for glaucoma.

PubMed

Ilka, Roya; Mohseni, Mojdeh; Kianirad, Mehran; Naseripour, Masood; Ashtari, Khadijeh; Mehravi, Bita

2018-04-01

Despite frequent scientific efforts, efficient ocular drug delivery is a major challenge for pharmaceutical scientists. Poor bioavailability of ophthalmic solutions can be overcome by using smart ophthalmic drug-delivery systems. In this research, loading and delivery of Timolol Maleate (TM) through the cornea by synthesized nanoparticles based on biopolymers (chitosan-alginate) were studied. The physico-chemical properties of these nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). Loading and release were evaluated by a UV-vis spectrometer and the ex vivo permeation study was carried out using the Franz Diffusion Cell and fluorescent microscopy studies. The results indicated that morphology and size of nanoparticles were spherical and in the range of 80-100nm. The loading capacity and encapsulation efficiency were about 42% and 94% respectively. They illustrated a burst release in the first hour followed by a slower and more sustained drug release during the next 24h. Also, the results indicated that the cornea penetration of TM loaded in nanoparticles was twice than that of TM. Hence, this nanocarrier can be considered as a suitable candidate for controlled TM delivery and release through the cornea. Copyright © 2017 Elsevier B.V. All rights reserved.

Sustained Pulmonary Delivery of a Water-Soluble Antibiotic Without Encapsulating Carriers.

PubMed

Ong, Winston; Nowak, Pawel; Cu, Yen; Schopf, Lisa; Bourassa, James; Enlow, Elizabeth; Moskowitz, Samuel M; Chen, Hongming

2016-03-01

Traditional polymeric nanoparticle formulations for prolonged local action during inhalation therapy are highly susceptible to muco-ciliary clearance. In addition, polymeric carriers are typically administered in high doses due to finite drug loading. For toxicological reasons, these carriers and their degradation byproducts are undesirable for inhalation therapy, particularly for chronic use, due to potential lung accumulation. We synthesized a novel, insoluble prodrug (MRPD) of a time-dependent β-lactam, meropenem, and formulated MRPD into mucus-penetrating crystals (MRPD-MPCs). After characterizing their mucus mobility (in vitro) and stability, we evaluated the lung pharmacokinetics of intratracheally-instilled MRPD-MPCs and a meropenem solution in guinea pigs. Meropenem levels rapidly declined in the lungs of guinea pigs receiving meropenem solution compared to those given MRPD-MPCs. At 9 h after dosing, drug levels in the lungs of animals that received meropenem solution dropped to 12 ng/mL, whereas those that received MRPD-MPCs maintained an average drug level of ≥1,065 ng/mL over a 12-h period. This work demonstrated that the combination of prodrug chemistry and mucus-penetrating platform created nanoparticles that produced sustained levels of meropenem in guinea pig lungs. This strategy represents a novel approach for sustained local drug delivery to the lung without using encapsulating matrices.

Clove essential oil-in-cyclodextrin-in-liposomes in the aqueous and lyophilized states: From laboratory to large scale using a membrane contactor.

PubMed

Sebaaly, Carine; Charcosset, Catherine; Stainmesse, Serge; Fessi, Hatem; Greige-Gerges, Hélène

2016-03-15

This work is dedicated to prepare liposomal dry powder formulations of inclusion complexes of clove essential oil (CEO) and its main component eugenol (Eug). Ethanol injection method and membrane contactor were applied to prepare liposomes at laboratory and large scale, respectively. Various liposomal formulations were tested: (1) free hydroxypropyl-β-cyclodextrin loaded liposomes; (2) drug in hydroxypropyl-β-cyclodextrin in liposomes (DCL); (3) DCL2 obtained by double loading technique, where the drug is added in the organic phase and the inclusion complex in the aqueous phase. Liposomes were characterized for their particle size, polydispersity index, Zeta potential, morphology, encapsulation efficiency of CEO components and Eug loading rate. Reproducible results were obtained with both injection devices. Compared to Eug-loaded liposomes, DCL and DCL2 improved the loading rate of Eug and possessed smaller vesicles size. The DPPH(•) scavenging activity of Eug and CEO was maintained upon incorporation of Eug and CEO into DCL and DCL2. Contrary to DCL2, DCL formulations were stable after 1 month of storage at 4°C and upon reconstitution of the dried lyophilized cakes. Hence, DCL in aqueous and lyophilized forms, are considered as a promising carrier system to preserve volatile and hydrophobic drugs enlarging their application in cosmetic, pharmaceutical and food industries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Substitution of Percutaneous Ethanol Injection with a Low Molecular Weight Peptide Gel Mimicking Chemoembolization for Cancer Therapy

PubMed Central

Xu, Long; Liang, Yan; Sun, Changzheng; Hao, Na; Yan, Jianqin; Gao, Wenxia; He, Bin

2017-01-01

In order to avoid the instability and quick separation between emulsifier and drug in the interventional chemoembolization, an injectable low molecular weight peptide gel (LMWG) was prepared to localize ethanol and chemotherapeutic for in situ synergistic therapy. The formation mechanism, rheological property and morphology of the LMWG were investigated by NMR, UV-vis, MS and SEM. The interaction between gelator and anticancer drug doxorubicin hydrochloride (DOX) was evaluated by fluorescence spectroscopy and its contribution on drug loading properties was demonstrated. The gel was non-toxic to both 3T3 fibroblasts and 4T1 breast cancer cells. DOX as well as ethanol were encapsulated in the gel and injected in breast cancer bearing mice with low drug dose (2.5 mg/kg body weight). The LMWG surrounded tumors act as a depot for ethanol release and release DOX to induce the apoptosis of cancer cells. With the combination of percutaneous ethanol injection (PEI) and chemotherapy, the DOX loaded LMWG exhibited great significance in necrosis of tumor tissue and exciting tumor inhibition efficiency. PMID:29071195

Stimuli-responsive protamine-based biodegradable nanocapsules for enhanced bioavailability and intracellular delivery of anticancer agents

NASA Astrophysics Data System (ADS)

Radhakrishnan, Krishna; Thomas, Midhun B.; Pulakkat, Sreeranjini; Gnanadhas, Divya P.; Chakravortty, Dipshikha; Raichur, Ashok M.

2015-08-01

Enzyme- and pH-responsive polyelectrolyte nanocapsules having diameters in the range of 200 ± 20 nm were fabricated by means of Layer-by-Layer assembly of biopolymers, protamine, and heparin, and then loaded with anticancer drug doxorubicin. The incorporation of the FDA-approved peptide drug protamine as a wall component rendered the capsules responsive to enzyme stimuli. The stimuli-responsive drug release from these nanocapsules was evaluated, and further modulation of capsule permeability to avoid premature release was demonstrated by crosslinking the wall components. The interaction of the nanocapsules with cancer cells was studied using MCF-7 breast cancer cells. These capsules were readily internalized and disintegrated inside the cells, culminating in the release of the loaded doxorubicin and subsequent cell death as observed by confocal microscopy and MTT Assay. The bioavailability studies performed using BALB/c mice revealed that the encapsulated doxorubicin exhibited enhanced bioavailability compared to free doxorubicin. Our results indicate that this stimuli-responsive system fabricated from clinically used FDA-approved molecules and exhibiting minimal premature release has great potential for drug-delivery applications.

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

PubMed Central

Ferro, Monica; Pastori, Nadia; Punta, Carlo; Melone, Lucio; Panzeri, Walter; Rossi, Barbara; Trotta, Francesco

2017-01-01

Two different formulations of cyclodextrin nanosponges (CDNS), obtained by polycondensation of β-cyclodextrin with ethylenediaminetetraacetic acid dianhydride (EDTAn), were treated with aqueous solutions of ibuprofen sodium salt (IbuNa) affording hydrogels that, after lyophilisation, gave two solid CDNS-drug formulations. 1H fast MAS NMR and 13C CP-MAS NMR spectra showed that IbuNa was converted in situ into its acidic and dimeric form (IbuH) after freeze-drying. 13C CP-MAS NMR spectra also indicated that the structure of the nanosponge did not undergo changes upon drug loading compared to the unloaded system. However, the 13C NMR spectra collected under variable contact time cross-polarization (VCT-CP) conditions showed that the polymeric scaffold CDNS changed significantly its dynamic regime on passing from the empty CDNS to the drug-loaded CDNS, thus showing that the drug encapsulation can be seen as the formation of a real supramolecular aggregate rather than a conglomerate of two solid components. Finally, the structural features obtained from the different solid-state NMR approaches reported matched the information from powder X-ray diffraction profiles. PMID:28228859

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy.

PubMed

Ferro, Monica; Castiglione, Franca; Pastori, Nadia; Punta, Carlo; Melone, Lucio; Panzeri, Walter; Rossi, Barbara; Trotta, Francesco; Mele, Andrea

2017-01-01

Two different formulations of cyclodextrin nanosponges (CDNS), obtained by polycondensation of β-cyclodextrin with ethylenediaminetetraacetic acid dianhydride (EDTAn), were treated with aqueous solutions of ibuprofen sodium salt (IbuNa) affording hydrogels that, after lyophilisation, gave two solid CDNS-drug formulations. 1 H fast MAS NMR and 13 C CP-MAS NMR spectra showed that IbuNa was converted in situ into its acidic and dimeric form (IbuH) after freeze-drying. 13 C CP-MAS NMR spectra also indicated that the structure of the nanosponge did not undergo changes upon drug loading compared to the unloaded system. However, the 13 C NMR spectra collected under variable contact time cross-polarization (VCT-CP) conditions showed that the polymeric scaffold CDNS changed significantly its dynamic regime on passing from the empty CDNS to the drug-loaded CDNS, thus showing that the drug encapsulation can be seen as the formation of a real supramolecular aggregate rather than a conglomerate of two solid components. Finally, the structural features obtained from the different solid-state NMR approaches reported matched the information from powder X-ray diffraction profiles.

Substitution of Percutaneous Ethanol Injection with a Low Molecular Weight Peptide Gel Mimicking Chemoembolization for Cancer Therapy.

PubMed

Xu, Long; Liang, Yan; Sun, Changzheng; Hao, Na; Yan, Jianqin; Gao, Wenxia; He, Bin

2017-01-01

In order to avoid the instability and quick separation between emulsifier and drug in the interventional chemoembolization, an injectable low molecular weight peptide gel (LMWG) was prepared to localize ethanol and chemotherapeutic for in situ synergistic therapy. The formation mechanism, rheological property and morphology of the LMWG were investigated by NMR, UV-vis, MS and SEM. The interaction between gelator and anticancer drug doxorubicin hydrochloride (DOX) was evaluated by fluorescence spectroscopy and its contribution on drug loading properties was demonstrated. The gel was non-toxic to both 3T3 fibroblasts and 4T1 breast cancer cells. DOX as well as ethanol were encapsulated in the gel and injected in breast cancer bearing mice with low drug dose (2.5 mg/kg body weight). The LMWG surrounded tumors act as a depot for ethanol release and release DOX to induce the apoptosis of cancer cells. With the combination of percutaneous ethanol injection (PEI) and chemotherapy, the DOX loaded LMWG exhibited great significance in necrosis of tumor tissue and exciting tumor inhibition efficiency.

Nano and microparticle engineering of water insoluble drugs using a novel spray-drying process.

PubMed

Schafroth, Nina; Arpagaus, Cordin; Jadhav, Umesh Y; Makne, Sushil; Douroumis, Dennis

2012-02-01

In the current study nano and microparticle engineering of water insoluble drugs was conducted using a novel piezoelectric spray-drying approach. Cyclosporin A (CyA) and dexamethasone (DEX) were encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) grades of different molecular weights. Spray-drying studies carried out with the Nano Spray Dryer B-90 employed with piezoelectric driven actuator. The processing parameters including inlet temperature, spray mesh diameter, sample flow rate, spray rate, applied pressure and sample concentration were examined in order to optimize the particle size and the obtained yield. The process parameters and the solute concentration showed a profound effect on the particle engineering and the obtained product yield. The produced powder presented consistent and reproducible spherical particles with narrow particle size distribution. Cyclosporin was found to be molecularly dispersed while dexamethasone was in crystalline state within the PLGA nanoparticles. Further evaluation revealed excellent drug loading, encapsulation efficiency and production yield. In vitro studies demonstrated sustained release patterns for the active substances. This novel spray-drying process proved to be efficient for nano and microparticle engineering of water insoluble active substances. Copyright © 2011 Elsevier B.V. All rights reserved.

Dual stimuli polysaccharide nanovesicles for conjugated and physically loaded doxorubicin delivery in breast cancer cells.

PubMed

Pramod, P S; Shah, Ruchira; Jayakannan, Manickam

2015-04-21

The present work reports the development of pH and enzyme dual responsive polysaccharide vesicular nano-scaffolds for the administration of doxorubicin via physical loading and polymer-drug conjugation to breast cancer cells. Dextran was suitably modified with a renewable resource 3-pentadecyl phenol unit through imine and aliphatic ester chemical linkages that acted as pH and esterase enzyme stimuli, respectively. These dual responsive polysaccharide derivatives self-organized into 200 ± 10 nm diameter nano-vesicles in water. The water soluble anticancer drug doxorubicin (DOX·HCl) was encapsulated in the hydrophilic pocket to produce core-loaded polysaccharide vesicles whereas chemical conjugation produced DOX anchored at the hydrophobic layer of the dextran nano-vesicles. In vitro studies revealed that about 70-80% of the drug was retained under circulatory conditions at pH = 7.4 and 37 °C. At a low pH of 6.0 to 5.0 and in the presence of esterase; both imine and ester linkages were cleaved instantaneously to release 100% of the loaded drugs. Cytotoxicity assays on Wild Type Mouse Embryonic Fibroblasts (WTMEFs) confirmed the non-toxicity of the newly developed dextran derivatives at up to 500 μg mL(-1) in PBS. MTT assays on fibroblast cells revealed that DOX·HCl loaded nano-vesicles exhibited better killing abilities than DOX conjugated polymer nano-vesicles. Both DOX loaded and DOX conjugated nano-vesicles were found to show significant killing in breast cancer cells (MCF 7). Confocal microscopy images confirmed the uptake of DOX loaded (or conjugated) nano-vesicles by cells compared to free DOX. Thus, the newly developed pH and enzyme dual responsive polysaccharide vesicular assemblies are potential drug vectors for the administration of DOX in both loaded and chemically conjugated forms for the efficient killing of breast cancer cells.

Self-Assembled pH-Responsive Polymeric Micelles for Highly Efficient, Noncytotoxic Delivery of Doxorubicin Chemotherapy To Inhibit Macrophage Activation: In Vitro Investigation.

PubMed

Liao, Zhi-Sheng; Huang, Shan-You; Huang, Jyun-Jie; Chen, Jem-Kun; Lee, Ai-Wei; Lai, Juin-Yih; Lee, Duu-Jong; Cheng, Chih-Chia

2018-04-26

Self-assembled pH-responsive polymeric micelles, a combination of hydrophilic poly(ethylene glycol) segments and hydrogen bonding interactions within a biocompatible polyurethane substrate, can spontaneously self-assemble into highly controlled, nanosized micelles in aqueous solution. These newly developed micelles exhibit excellent pH-responsive behavior and biocompatibility, highly controlled drug (doxorubicin; DOX) release behavior, and high drug encapsulation stability in different aqueous environments, making the micelles highly attractive potential candidates for safer, more effective drug delivery in applications such as cancer chemotherapy. In addition, in vitro cell studies revealed the drug-loaded micelles possessed excellent drug entrapment stability and low cytotoxicity toward macrophages under normal physiological conditions (pH 7.4, 37 °C). When the pH of the culture media was reduced to 6.0 to mimic the acidic tumor microenvironment, the drug-loaded micelles triggered rapid release of DOX within the cells, which induced potent antiproliferative and cytotoxic effects in vitro. Importantly, fluorescent imaging and flow cytometric analyses confirmed the DOX-loaded micelles were efficiently delivered into the cytoplasm of the cells via endocytosis and then subsequently gradually translocated into the nucleus. Therefore, these multifunctional micelles could serve as delivery vehicles for precise, effective, controlled drug release to prevent accumulation and activation of tumor-promoting tumor-associated macrophages in cancer tissues. Thus, this unique system may offer a potential route toward the practical realization of next-generation pH-responsive therapeutic delivery systems.

Comparison of generation 3 polyamidoamine dendrimer and generation 4 polypropylenimine dendrimer on drug loading, complex structure, release behavior, and cytotoxicity

PubMed Central

Shao, Naimin; Su, Yunzhang; Hu, Jingjing; Zhang, Jiahai; Zhang, Hongfeng; Cheng, Yiyun

2011-01-01

Background Polyamidoamine (PAMAM) and polypropylenimine (PPI) dendrimers are the commercially available and most widely used dendrimers in pharmaceutical sciences and biomedical engineering. In the present study, the loading and release behaviors of generation 3 PAMAM and generation 4 PPI dendrimers with the same amount of surface amine groups (32 per dendrimer) were compared using phenylbutazone as a model drug. Methods The dendrimer-phenylbutazone complexes were characterized by 1H nuclear magnetic resonance and nuclear Overhauser effect techniques, and the cytotoxicity of each dendrimer was evaluated. Results Aqueous solubility results suggest that the generation 3 PAMAM dendrimer has a much higher loading ability towards phenylbutazone in comparison with the generation 4 PPI dendrimer at high phenylbutazone-dendrimer feeding ratios. Drug release was much slower from the generation 3 PAMAM matrix than from the generation 4 PPI dendrimer. In addition, the generation 3 PAMAM dendrimer is at least 50-fold less toxic than generation 4 PPI dendrimer on MCF-7 and A549 cell lines. Conclusion Although the nuclear Overhauser effect nuclear magnetic resonance results reveal that the generation 4 PPI dendrimer with a more hydrophobic interior encapsulates more phenylbutazone, the PPI dendrimer-phenylbutazone inclusion is not stable in aqueous solution, which poses a great challenge during drug development. PMID:22267921

Physical and biological characterization of sericin-loaded copolymer liposomes stabilized by polyvinyl alcohol.

PubMed

Suktham, Kunat; Koobkokkruad, Thongchai; Saesoo, Somsak; Saengkrit, Nattika; Surassmo, Suvimol

2016-12-01

Sericin protein (SP) is widely used as a nutrient biomaterial for biomedical and cosmeceutical applications although it shows low stability to heat and light. To overcome these problems and add value to wastewater from the silk industry, sericin protein was recovered as sericin-loaded copolymer-liposomes (SP-PVA-LP), prepared through thin film hydration. The size and morphology of the liposomes were investigated using dynamic light scattering (DLS), and electron microscopy (SEM and TEM). The particle size, liposome surface morphology and encapsulation efficiency of SP were dependent on PVA concentration. The hydrodynamic size of the nanoparticles was between 200 and 400nm, with the degree of negative charge contingent on sericin loading. SEM and TEM images confirmed the mono-dispersity, and spherical nature of the particles, with FTIR measurements confirming the presence of surface bound PVA. Exposure of liposomes to 500ppm sericin highlighted a dependence of encapsulation efficiency on PVA content; 2% surface PVA proved the optimal level for sericin loading. Cytotoxicity and viability assays revealed that SP-loaded surface modified liposomes promote cellular attachment and proliferation of human skin fibroblasts without adverse toxic effects. Surface modified copolymer liposomes show high performance in maintaining structural stability, and promoting enhancements in the solubility and bio-viability of sericin. Taken together, these biocompatible constructs allow for effective controlled release, augmenting sericin activity and resulting in effective drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Mucoadhesive Microparticles for Gastroretentive Delivery: Preparation, Biodistribution and Targeting Evaluation

PubMed Central

Hou, Jing-Yi; Gao, Li-Na; Meng, Fan-Yun; Cui, Yuan-Lu

2014-01-01

The aim of this research was to prepare and characterize alginate-chitosan mucoadhesive microparticles containing puerarin. The microparticles were prepared by an emulsification-internal gelatin method using a combination of chitosan and Ca2+ as cationic components and alginate as anions. Surface morphology, particle size, drug loading, encapsulation efficiency and swelling ratio, in vitro drug released, in vitro evaluation of mucoadhesiveness and Fluorescence imaging of the gastrointestinal tract were determined. After optimization of the formulation, the encapsulation efficiency was dramatically increased from 70.3% to 99.2%, and a highly swelling ratio was achieved with a change in particle size from 50.3 ± 11.2 μm to 124.7 ± 25.6 μm. In ethanol induced gastric ulcers, administration of puerarin mucoadhesive microparticles at doses of 150 mg/kg, 300 mg/kg, 450 mg/kg and 600 mg/kg body weight prior to ethanol ingestion significantly protected the stomach ulceration. Consequently, significant changes were observed in inflammatory cytokines, such as prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and interleukin1β (IL-1β), in stomach tissues compared with the ethanol control group. In conclusion, core-shell type pH-sensitive mucoadhesive microparticles loaded with puerarin could enhance puerarin bioavailability and have the potential to alleviate ethanol-mediated gastric ulcers. PMID:25470180

Chitosan encapsulation of essential oil "cocktails" with well-defined binary Zn(II)-Schiff base species targeting antibacterial medicinal nanotechnology.

PubMed

Halevas, Eleftherios; Nday, Christiane M; Chatzigeorgiou, Evanthia; Varsamis, Vasileios; Eleftheriadou, Despoina; Jackson, Graham E; Litsardakis, Georgios; Lazari, Diamanto; Ypsilantis, Konstantinos; Salifoglou, Athanasios

2017-11-01

The advent of biodegradable nanomaterials with enhanced antibacterial activity stands as a challenge to the global research community. In an attempt to pursue the development of novel antibacterial medicinal nanotechnology, we herein a) synthesized ionic-gelated chitosan nanoparticles, b) compared and evaluated the antibacterial activity of essential oils extracted from nine different herbs (Greek origin) and their combinations with a well-defined antibacterial Zn(II)-Schiff base compound, and c) encapsulated the most effective hybrid combination of Zn(II)-essential oils inside the chitosan matrix, thereby targeting well-formulated nanoparticles of distinct biological impact. The empty and loaded chitosan nanoparticles were physicochemically characterized by FT-IR, Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), with the entrapment and drug release studies being conducted through UV-Visible and atomic absorption techniques. The antimicrobial properties of the novel hybrid materials were demonstrated against Gram positive (S. aureus, B. subtilis, and B. cereus) and Gram negative (E. coli and X. campestris) bacteria using modified agar diffusion methods. The collective physicochemical profile of the hybrid Zn(II)-essential oil cocktails, formulated so as to achieve optimal activity when loaded to chitosan nanoparticles, signifies the importance of design in the development of efficient nanomedicinal pharmaceuticals a) based on both natural products and biogenic metal ionic cofactors, and b) targeting bacterial infections and drug resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Formulation and Evaluation of Organogels Containing Hyaluronan Microparticles for Topical Delivery of Caffeine.

PubMed

Simsolo, Erol Eli; Eroğlu, İpek; Tanrıverdi, Sakine Tuncay; Özer, Özgen

2018-04-01

Cellulite is a dermal disorder including the extracellular matrix, the lymphatic and microcirculatory systems and the adipose tissue. Caffeine is used as the active moiety depending its preventive effect on localization of fat in the cellular structure. Hyaluronic acid (hyaluronan-HA) is a natural constituent of skin that generates formation and poliferation of new cells having a remarkable moisturizing ability. The aim of this study is to formulate HA microparticles loaded with caffeine via spray-drying method. Resulting microparticle formulations (33.97 ± 0.3 μm, span < 2, 88.56 ± 0.42% encapsulation efficiency) were distributed in lecithin organogels to maintain the proper viscosity for topical application. Following the characterization and cell culture studies, in vitro drug release and ex vivo permeation studies were performed. The accumulated amount of caffeine was twice higher than the aqueous solution for the microparticle-loaded organogels at 24 h (8262,673 μg/cm 2 versus 4676,691 μg/cm 2 ). It was related to the sustained behaviour of caffeine release from the microparticles. As a result, lecithin organogel containing HA-encapsulated microparticles could be considered as suitable candidate formulations for efficient topical drug delivery system of caffeine. In addition to that, synergistic effect of this combination appears as a promising approach for long-acting treatment of cellulite.

Design, characterization, and in vitro cellular inhibition and uptake of optimized genistein-loaded NLC for the prevention of posterior capsular opacification using response surface methodology.

PubMed

Zhang, Wenji; Li, Xuedong; Ye, Tiantian; Chen, Fen; Sun, Xiao; Kong, Jun; Yang, Xinggang; Pan, Weisan; Li, Sanming

2013-09-15

This study was to design an innovative nanostructured lipid carrier (NLC) for drug delivery of genistein applied after cataract surgery for the prevention of posterior capsular opacification. NLC loaded with genistein (GEN-NLC) was produced with Compritol 888 ATO, Gelucire 44/14 and Miglyol 812N, stabilized by Solutol(®) HS15 by melt emulsification method. A 2(4) central composite design of 4 independent variables was performed for optimization. Effects of drug concentration, Gelucire 44/14 concentration in total solid lipid, liquid lipid concentration, and surfactant concentration on the mean particle size, polydispersity index, zeta potential and encapsulation efficiency were investigated. Analysis of variance (ANOVA) statistical test was used to assess the optimization. The optimized GEN-NLC showed a homogeneous particle size of 90.16 nm (with PI=0.33) of negatively charged surface (-25.08 mv) and high encapsulation efficiency (91.14%). Particle morphology assessed by TEM revealed a spherical shape. DSC analyses confirmed that GEN was mostly entrapped in amorphous state. In vitro release experiments indicated a prolonged and controlled genistein release for 72 h. In vitro growth inhibition assay showed an effective growth inhibition of GEN-NLCs on human lens epithelial cells (HLECs). Preliminary cellular uptake test proved a enhanced penetration of genistein into HLECs when delivered in NLC. Copyright © 2013 Elsevier B.V. All rights reserved.

Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630

PubMed Central

Wu, Xiaoyan; Ge, Weihong; Shao, Tengfei; Wu, Weijun; Hou, Jian; Cui, Li; Wang, Jing; Zhang, Zhenghai

2017-01-01

Biochanin A (BCA), a natural dietary isoflavone, has been reported to show anticancer activities. However, its low biological availability and poor aqueous solubility limit its usefulness as a chemotherapeutic agent. We developed BCA-loaded micelles with Pluronic F127 and Plasdone S630 (BCA-FS). The optimized, spherical-shaped BCA-FS was obtained at a ratio of 1:1 (F127:S630). The particle size was 25.17±1.2 nm, and the zeta potential was −10.9±0.24 mV. BCA solubility in water increased to 5.0 mg/mL after encapsulation, and the drug-loading efficiency was 5.88%±0.76%. In vitro release experiments showed a delayed release of BCA from the mixed micelles. Furthermore, the BCA absorption permeability across a Caco-2 cell monolayer from the apical side to the basolateral side increased by 54% in BCA-FS. A pharmacokinetics evaluation showed a 2.16-fold increase in the relative oral bioavailability of BCA-FS compared with raw BCA, indicating that the mixed micelles may promote absorption in the gastrointestinal tract. A gastrointestinal safety assay was used to assess the reliability and safety of BCA-FS. On the basis of these findings, we conclude that this simple nanomicelle system could be leveraged to deliver BCA and other hydrophobic drugs. PMID:28260893

Methotrexate loading in chitosan nanoparticles at a novel pH: Response surface modeling, optimization and characterization.

PubMed

Hashad, Rania A; Ishak, Rania A H; Geneidi, Ahmed S; Mansour, Samar

2016-10-01

The aim of this study was to assess the feasibility of employing a novel but critical formulation pH (6.2) to encapsulate an anionic model drug (methotrexate, MTX) into chitosan(Cs)-tripolyphosphate nanoparticles(NPs). A response surface methodology using a three-level full factorial design was applied studying the effects of two independent variables namely; Cs concentration and MTX concentration. The responses investigated were the entrapment efficiency (EE%), mean hydrodynamic particle size (PS), polydispersity index (PDI) and zeta potential (ZP). In order to simultaneously optimize the series of models obtained, the desirability function approach was applied with a goal to produce high percent of MTX encapsulated into highly charged Cs-TPP NPs of homogenous optimum PS. MTX-loaded CsNPs were successfully prepared at the novel pH applied. The suggested significant models were found quadratic for EE, PS and ZP responses, while 2-factor interaction model for PDI. The optimization overlay graph showed that the maximum global desirability, D=0.856, was reached when the conditions were set at high Cs and MTX concentration. Thus, the use of such optimized conditions, at this novel pH, achieved a maximum drug EE% (73.38%) into NPs characterized by optimum PS (232.6nm), small PDI value (0.195) and highly surface charged (+18.4mV). Copyright © 2016 Elsevier B.V. All rights reserved.

Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630.

PubMed

Wu, Xiaoyan; Ge, Weihong; Shao, Tengfei; Wu, Weijun; Hou, Jian; Cui, Li; Wang, Jing; Zhang, Zhenghai

2017-01-01

Biochanin A (BCA), a natural dietary isoflavone, has been reported to show anticancer activities. However, its low biological availability and poor aqueous solubility limit its usefulness as a chemotherapeutic agent. We developed BCA-loaded micelles with Pluronic F127 and Plasdone S630 (BCA-FS). The optimized, spherical-shaped BCA-FS was obtained at a ratio of 1:1 (F127:S630). The particle size was 25.17±1.2 nm, and the zeta potential was -10.9±0.24 mV. BCA solubility in water increased to 5.0 mg/mL after encapsulation, and the drug-loading efficiency was 5.88%±0.76%. In vitro release experiments showed a delayed release of BCA from the mixed micelles. Furthermore, the BCA absorption permeability across a Caco-2 cell monolayer from the apical side to the basolateral side increased by 54% in BCA-FS. A pharmacokinetics evaluation showed a 2.16-fold increase in the relative oral bioavailability of BCA-FS compared with raw BCA, indicating that the mixed micelles may promote absorption in the gastrointestinal tract. A gastrointestinal safety assay was used to assess the reliability and safety of BCA-FS. On the basis of these findings, we conclude that this simple nanomicelle system could be leveraged to deliver BCA and other hydrophobic drugs.

Nanospheres Encapsulating Anti-Leishmanial Drugs for Their Specific Macrophage Targeting, Reduced Toxicity, and Deliberate Intracellular Release

PubMed Central

Shukla, Anil Kumar; Patra, Sanjukta

2012-01-01

Abstract The current work focuses on the study of polymeric, biodegradable nanoparticles (NPs) for the encapsulation of doxorubicin and mitomycin C (anti-leishmanial drugs), and their efficient delivery to macrophages, the parasite's home. The biodegradable polymer methoxypoly-(ethylene glycol)-b-poly (lactic acid) (MPEG-PLA) was used to prepare polymeric NPs encapsulating doxorubicin and mitomycin C. The morphology, mean diameter, and surface area of spherical NPs were determined by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and BET surface area analysis. X-ray diffraction was performed to validate drug encapsulation. An in vitro release profile of the drugs suggested a fairly slow release. These polymeric NPs were efficiently capable of releasing drug inside macrophages at a slower pace than the free drug, which was monitored by epi-fluorescence microscopy. Encapsulation of doxorubicin and mitomycin C into NPs also decreases cellular toxicity in mouse macrophages (J774.1A). PMID:22925019

Double emulsion solvent evaporation techniques used for drug encapsulation.

PubMed

Iqbal, Muhammad; Zafar, Nadiah; Fessi, Hatem; Elaissari, Abdelhamid

2015-12-30

Double emulsions are complex systems, also called "emulsions of emulsions", in which the droplets of the dispersed phase contain one or more types of smaller dispersed droplets themselves. Double emulsions have the potential for encapsulation of both hydrophobic as well as hydrophilic drugs, cosmetics, foods and other high value products. Techniques based on double emulsions are commonly used for the encapsulation of hydrophilic molecules, which suffer from low encapsulation efficiency because of rapid drug partitioning into the external aqueous phase when using single emulsions. The main issue when using double emulsions is their production in a well-controlled manner, with homogeneous droplet size by optimizing different process variables. In this review special attention has been paid to the application of double emulsion techniques for the encapsulation of various hydrophilic and hydrophobic anticancer drugs, anti-inflammatory drugs, antibiotic drugs, proteins and amino acids and their applications in theranostics. Moreover, the optimized ratio of the different phases and other process parameters of double emulsions are discussed. Finally, the results published regarding various types of solvents, stabilizers and polymers used for the encapsulation of several active substances via double emulsion processes are reported. Copyright © 2015 Elsevier B.V. All rights reserved.

Cytotoxicity of solid lipid nanoparticles and nanostructured lipid carriers containing the local anesthetic dibucaine designed for topical application

NASA Astrophysics Data System (ADS)

Barbosa, R. M.; da Silva, C. M. G.; Bella, T. S.; de Araújo, D. R.; Marcato, P. D.; Durán, N.; de Paula, E.

2013-04-01

Dibucaine (DBC) is powerful long-lasting local anesthetic, but it is also considered fairly toxic to the CNS. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have attracted attention as carriers for drug delivery. The aim of this study was to develop and to evaluate the cytotoxic activity of DBC-loaded SLN and NLC against 3T3 fibroblast and HaCat keratinocyte cells. The SLN and NLC had myristyl myristate and Liponate®GC as their lipid matrices, respectively, plus a surfactant. SLN and NLC were characterized in terms in their diameter, size distribution, surface charge and DBC encapsulation efficiency. The particle size of SLN and NLC were around 234.33 and 166.62 nm, respectively. The polydispersity index was kept below 0.2 for both nanomaterials. Negative surface charges were observed for both nanoparticles, which decreased in the presence of the anesthetic. Encapsulation efficiency reached 76% and 90%, respectively, in SLN and NLC. DBC alone was found to be toxic to 3T3 and HaCat cells in culture. However, NLC and SLN loaded DBC decreased its intrinsic cytotoxic effect against 3T3 and HaCat cells. In conclusion, encapsulation of DBC in SLN and NLC decreased the in vitro toxicity of the local anesthetic, indicating the potential of these nanocarriers for clinical applications.

A nanoparticulate drug-delivery system for rivastigmine: physico-chemical and in vitro biological characterization.

PubMed

Craparo, Emanuela Fabiola; Pitarresi, Giovanna; Bondì, Maria Luisa; Casaletto, Maria Pia; Licciardi, Mariano; Giammona, Gaetano

2008-03-10

The preparation and characterization of surface-PEGylated polymeric nanoparticles are described. These systems were obtained by UV irradiation of PHM and PHM-PEG(2000) as an inverse microemulsion, using an aqueous solution of the PHM/PHM-PEG(2000) copolymer mixture as the internal phase and triacetin saturated with water as the external phase, and characterized by dimensional analysis, zeta-potential measurements and XPS. in vitro biological tests demonstrated their cell compatibility and their ability to escape from phagocytosis. Rivastigmine was encapsulated into the nanoparticle structure and drug-release profiles from loaded samples were investigated in PBS at pH = 7.4 and human plasma.

Biocompatible microemulsions for fabrication of glyceryl monostearate solid lipid nanoparticles (SLN) of tretinoin.

PubMed

Shah, Kumar A; Joshi, Medha D; Patravale, Vandana B

2009-08-01

The objective of the present investigation was to fabricate glyceryl monostearate SLN by employing a biocompatible microemulsion as a template. Biocompatible excipients such as Tween 20 (as a surfactant) and Transcutol P (a cosourfactant) (at different K(m) ratios) were selected for the fabrication of microemulsions. Pseudo-ternary phase diagrams were plotted to identify the area of the microemulsion existence. Glyceryl monostearate SLN were fabricated by dispersing the microemulsion (maintained at 65 degrees C) into cold water (maintained at 2-3 degrees C). The particle size of the SLN was determined by photon correlation spectroscopy. Tretinoin, a lipophilic anti-acne agent was incorporated into SLN as a model drug. The encapsulation efficiency of tretinoin in the SLN was determined by using Nanosep ultrafilteration device at different lipid loads viz. 1%, 1.5% and 2%. Glyceryl monostearate SLN fabricated from biocompatible microemulsion template exhibited average particle size of 175 nm and polydispersity index of 0.833. Tretinoin could be successfully incorporated into SLN and the encapsulation efficiency ranged from 37-48% at different lipid loads.

Evaluation of the Combined Effect of Recombinant High-Density Lipoprotein Carrier and the Encapsulated Lovastatin in RAW264.7 Macrophage Cells Based on the Median-Effect Principle.

PubMed

Jiang, Cuiping; Zhao, Yi; Yang, Yun; He, Jianhua; Zhang, Wenli; Liu, Jianping

2018-03-05

Recombinant high-density lipoprotein (rHDL) displays a similar anti-atherosclerotic effect with native HDL and could also be served as a carrier of cardiovascular drug for atherosclerotic plaque targeting. In our previous studies, rHDL has shown a more potent anti-atherosclerotic efficacy as compared to the other conventional nanoparticles with a payload of lovastatin (LS). Therefore, we hypothesized that a synergistic anti-atherosclerotic effect of the rHDL carrier and the encapsulated LS might exist. In this study, the dose-effect relationships and the combined effect of the rHDL and LS were quantitatively evaluated in RAW 264.7 macrophage cells using the median-effect analysis, in which the rHDL carrier was regarded as a drug combined. Median-effect analysis suggested that rHDL and LS exerted a desirable synergistic inhibition on the oxLDL internalization at a ratio of 6:1 ( D m,LS : D m,rHDL ) in RAW 264.7 macrophage cells. About 50% of the reduction on the intracellular lipid contents was found when RAW264.7 cells were treated with LS-loaded rHDLs at their respective median-effect dose ( D m ) concentrations and a synergistic effect on the mediating cholesterol efflux was also observed, which verified the accuracy of the results obtained from the median-effect analysis. The mechanism underlying the synergistic effect of the rHDL carrier and the drug might be attributed to their potent inhibitory effects on SR-A expression. In conclusion, the median-effect analysis was proven to be a feasible method to quantitatively evaluate the synergistic effect of the biofunctional carrier and the drug encapsulated.

Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

PubMed

Lau, Esther T L; Johnson, Stuart K; Williams, Barbara A; Mikkelsen, Deirdre; McCourt, Elizabeth; Stanley, Roger A; Mereddy, Ram; Halley, Peter J; Steadman, Kathryn J

2017-05-19

Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

Microparticles prepared from sulfenamide-based polymers

PubMed Central

D’Mello, Sheetal R.; Yoo, Jun; Bowden, Ned B.; Salem, Aliasger K.

2015-01-01

Polysulfenamides (PSN), with a SN linkage (RSNR2) along the polymer backbone, are a new class of biodegradable and biocompatible polymers. These polymers were unknown prior to 2012 when their synthesis and medicinally relevant properties were reported. The aim of this study was to develop microparticles as a controlled drug delivery system using polysulfenamide as the matrix material. The microparticles were prepared by a water-in-oil-in-water double emulsion solvent evaporation method. For producing drug-loaded particles, FITC-dextran was used as a model hydrophilic compound. At the optimal formulation conditions, the external morphology of the PSN microparticles was examined by scanning electron microscopy to show the formation of smooth-surfaced spherical particles with low polydispersity. The microparticles had a net negative surface charge (−23 mV) as analyzed by the zetasizer. The drug encapsulation efficiency of the particles and the drug loading were found to be dependent on the drug molecular weight, amount of FITC-dextran used in fabricating FITC-dextran loaded microparticles, concentration of PSN and surfactant, and volume of the internal and external water phases. FITC-dextran was found to be distributed throughout the PSN microparticles and was released in an initial burst followed by more continuous release over time. Confocal laser scanning microscopy was used to qualitatively observe the cellular uptake of PSN microparticles and indicated localization of the particles in both the cytoplasm and the nucleus. PMID:23862723

An Extrusion Spheronization Approach to Enable a High Drug Load Formulation of a Poorly Soluble Drug with a Low Melting Surfactant.

PubMed

Tatavarti, Aditya; Kesisoglou, Filippos

2015-11-01

Vitamin E tocopherol polyethylene glycol succinate (TPGS) is a non-ionic surface active agent, known to enhance the bioavailability of lipophilic compounds via wettability, solubility, and in some cases permeability enhancement. MK-0536 is an anti-retroviral drug with poor wettability and solubility and a high dose. Based on pharmacokinetic studies in dogs and humans, use of vitamin E TPGS in oral solid formulations of MK-0536 provides desired PK characteristics. The use of vitamin E TPGS, however, in solid dosage forms is limited because of the processing challenges resulting from its waxy nature and low melting temperature (∼37°C). The current study, for the first time, demonstrates the use of an alternative low pressure extrusion and spheronization approach to enable high loadings of the poorly soluble, poorly compactable drug and relatively high levels of vitamin E TPGS. This approach not only aided in mitigating processing challenges arising from most high energy process steps such as milling, compression, and coating, but also enabled a higher drug load formulation that provided superior bioperformance relative to a conventional high shear wet granulated formulation. An encapsulated dosage form consisting of pellets prepared by extrusion spheronization with 75% (w/w) MK-0536 and 10% (w/w) vitamin E TPGS was developed. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Solid lipid microparticles containing loratadine prepared using a Micromixer.

PubMed

Milak, Spomenka; Medlicott, Natalie; Tucker, Ian G

2006-12-01

Solid lipid microparticles were investigated as a taste-masking approach for a lipophilic weak base in a suspension. The idea was that the drug concentration in the aqueous phase of a suspension might be reduced by its partitioning into the solid lipid particles. Loratadine, as a model drug, was used to prepare Precirol ATO 5 microparticles by a Micromixer. The effects of three process variables: drug loading, PVA concentration and water/lipid ratio on the microparticle size, encapsulation efficiency, surface appearance, in-vitro release and drug partitioning in a suspension were studied. Loratadine release was slow in simulated saliva and very fast at the pH of stomach. In suspension of loratadine lipid microparticles, drug was released into the aqueous phase to the same concentration as in a drug suspension. Therefore, the usefulness of these microparticles for taste-masking in liquids is limited. However, they might be useful for taste-masking in solid dosage forms.

Investigation of drug loading and in vitro release mechanisms of insulin-lauryl sulfate complex loaded PLGA nanoparticles.

PubMed

Shi, K; Cui, F; Yamamoto, H; Kawashima, Y

2008-12-01

Insulin, a water soluble peptide hormone, was hydrophobically ion-paired with sodium lauryl sulfate (SDS) at the stoichiometric molar ratio of 6:1. The obtained insulin-SDS complex precipitation was subsequently formulated in biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles by a modified spontaneous emulsion solvent diffusion method. Compared with a conventional method for free insulin encapsulation, direct dissolution of SDS-paired insulin in the non-aqueous organic phase led to an increase in drug recovery from 42.5% to 89.6%. The more hydrophobic complex contributes to the improved affinity of insulin to the polymer matrix, resulting in a higher drug content in the nanoparticles. The drug loading was investigated by determining initial burst release at the first 30 min. The results showed that 64.8% of recovered drug were preferentially surface bound on complex loaded nanoparticles. The in vitro drug release was characterized by an initial burst and subsequent delayed release in dissolution media of deionized water and phosphate buffer saline (PBS). Compared with that in PBS, nanoparticles in deionized water medium presented very low initial burst release (15% vs. 65%) and incomplete cumulative release (25% vs. 90%) of the drug. In addition, dialysis experiments were performed to clarify the form of the released insulin in the dissolution media. The results suggested that the ion-pair complex was sensitive to ionic strength, insulin was released from the particular matrix as complex form and subsequently suffered dissociation from SDS in buffer saline. Moreover, the in vivo bioactivity of the SDS-paired insulin and nanoparticulate formulations were evaluated in mice by estimation of their blood sugar levels. The results showed that the bioactivity of insulin was unaltered after the ion-pairing process.

Complete Regression of Xenograft Tumors upon Targeted Delivery of Paclitaxel via Π-Π Stacking Stabilized Polymeric Micelles

PubMed Central

Shi, Yang; van der Meel, Roy; Theek, Benjamin; Blenke, Erik Oude; Pieters, Ebel H.E.; Fens, Marcel H.A.M.; Ehling, Josef; Schiffelers, Raymond M.; Storm, Gert; van Nostrum, Cornelus F.; Lammers, Twan; Hennink, Wim E.

2015-01-01

Treatment of cancer patients with taxane-based chemotherapeutics, such as paclitaxel (PTX), is complicated by their narrow therapeutic index. Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of PTX, as they can be tailored to encapsulate large amounts of hydrophobic drugs and achieve prolonged circulation kinetics. As a result, PTX deposition in tumors is increased while drug exposure to healthy tissues is reduced. However, many PTX-loaded micelle formulations suffer from low stability and fast drug release in the circulation, limiting their suitability for systemic drug targeting. To overcome these limitations, we have developed paclitaxel (PTX)-loaded micelles which are stable without chemical crosslinking and covalent drug attachment. These micelles are characterized by excellent loading capacity and strong drug retention, attributed to π-π stacking interaction between PTX and the aromatic groups of the polymer chains in the micellar core. The micelles are based on methoxy poly(ethylene glycol)-b-(N-(2-benzoyloxypropyl) methacrylamide) (mPEG-b-p(HPMAm-Bz)) block copolymers, which improved the pharmacokinetics and the biodistribution of PTX, and substantially increased PTX tumor accumulation (by more than 2000%; as compared to Taxol® or control micellar formulations). Improved biodistribution and tumor accumulation were confirmed by hybrid μCT-FMT imaging using near-infrared labeled micelles and payload. The PTX-loaded micelles were well tolerated at different doses while they induced complete tumor regression in two different xenograft models (i.e. A431 and MDA-MB-468). Our findings consequently indicate that π-π stacking-stabilized polymeric micelles are promising carriers to improve the delivery of highly hydrophobic drugs to tumors and to increase their therapeutic index. PMID:25831471

Preparation and in vitro characterization of 9-nitrocamptothecin-loaded long circulating nanoparticles for delivery in cancer patients.

PubMed

Derakhshandeh, Katayoun; Soheili, Marzieh; Dadashzadeh, Simin; Saghiri, Reza

2010-08-09

The purpose in this study was to investigate poly(ethylene glycol)-modified poly (d,l-lactide-co-glycolide) nanoparticles (PLGA-PEG-NPs) loading 9-nitrocamptothecin (9-NC) as a potent anticancer drug. 9-NC is an analog of the natural plant alkaloid camptothecin that has shown high antitumor activity and is currently in the end stage of clinical trial. Unfortunately, at physiological pH, these potent agents undergo a rapid and reversible hydrolysis with the loss of antitumor activity. Previous researchers have shown that the encapsulation of this drug in PLGA nanoparticles could increase its stability and release profile. In this research we investigated PLGA-PEG nanoparticles and their effect on in vitro characteristics of this labile drug. 9-NC-PLGA-PEG nanoparticles with particle size within the range of 148.5 ± 30 nm were prepared by a nanoprecipitation method. The influence of four different independent variables (amount of polymer, percent of emulsifier, internal phase volume, and external phase volume) on nanoparticle drug-loading was studied. Differential scanning calorimetry and X-ray diffractometry were also evaluated for physical characterizing. The results of optimized formulation showed a narrow size distribution, suitable zeta potential (+1.84), and a drug loading of more than 45%. The in vitro drug release from PLGA-PEG NPs showed a sustained release pattern of up to 120 hours and comparing with PLGA-NPs had a significant decrease in initial burst effect. These experimental results indicate that PLGA-PEG-NPs (versus PLGA-NPs) have a better physicochemical characterization and can be developed as a drug carrier in order to treat different malignancies.

Preparation and in vitro characterization of 9-nitrocamptothecin-loaded long circulating nanoparticles for delivery in cancer patients

PubMed Central

Derakhshandeh, Katayoun; Soheili, Marzieh; Dadashzadeh, Simin; Saghiri, Reza

2010-01-01

The purpose in this study was to investigate poly(ethylene glycol)-modified poly (d,l-lactide-co-glycolide) nanoparticles (PLGA-PEG-NPs) loading 9-nitrocamptothecin (9-NC) as a potent anticancer drug. 9-NC is an analog of the natural plant alkaloid camptothecin that has shown high antitumor activity and is currently in the end stage of clinical trial. Unfortunately, at physiological pH, these potent agents undergo a rapid and reversible hydrolysis with the loss of antitumor activity. Previous researchers have shown that the encapsulation of this drug in PLGA nanoparticles could increase its stability and release profile. In this research we investigated PLGA-PEG nanoparticles and their effect on in vitro characteristics of this labile drug. 9-NC-PLGA-PEG nanoparticles with particle size within the range of 148.5 ± 30 nm were prepared by a nanoprecipitation method. The influence of four different independent variables (amount of polymer, percent of emulsifier, internal phase volume, and external phase volume) on nanoparticle drug-loading was studied. Differential scanning calorimetry and X-ray diffractometry were also evaluated for physical characterizing. The results of optimized formulation showed a narrow size distribution, suitable zeta potential (+1.84), and a drug loading of more than 45%. The in vitro drug release from PLGA-PEG NPs showed a sustained release pattern of up to 120 hours and comparing with PLGA-NPs had a significant decrease in initial burst effect. These experimental results indicate that PLGA-PEG-NPs (versus PLGA-NPs) have a better physicochemical characterization and can be developed as a drug carrier in order to treat different malignancies. PMID:20957168

Imipenem/cilastatin encapsulated polymeric nanoparticles for destroying carbapenem-resistant bacterial isolates.

PubMed

Shaaban, Mona I; Shaker, Mohamed A; Mady, Fatma M

2017-04-11

Carbapenem-resistance is an extremely growing medical threat in antibacterial therapy as the incurable resistant strains easily develop a multi-resistance action to other potent antimicrobial agents. Nonetheless, the protective delivery of current antibiotics using nano-carriers opens a tremendous approach in the antimicrobial therapy, allowing the nano-formulated antibiotics to beat these health threat pathogens. Herein, we encapsulated imipenem into biodegradable polymeric nanoparticles to destroy the imipenem-resistant bacteria and overcome the microbial adhesion and dissemination. Imipenem loaded poly Ɛ-caprolactone (PCL) and polylactide-co-glycolide (PLGA) nanocapsules were formulated using double emulsion evaporation method. The obtained nanocapsules were characterized for mean particle diameter, morphology, loading efficiency, and in vitro release. The in vitro antimicrobial and anti adhesion activities were evaluated against selected imipenem-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa clinical isolates. The obtained results reveal that imipenem loaded PCL nano-formulation enhances the microbial susceptibility and antimicrobial activity of imipenem. The imipenem loaded PCL nanoparticles caused faster microbial killing within 2-3 h compared to the imipenem loaded PLGA and free drug. Successfully, PCL nanocapsules were able to protect imipenem from enzymatic degradation by resistant isolates and prevent the emergence of the resistant colonies, as it lowered the mutation prevention concentration of free imipenem by twofolds. Moreover, the imipenem loaded PCL eliminated bacterial attachment and the biofilm assembly of P. aeruginosa and K. pneumoniae planktonic bacteria by 74 and 78.4%, respectively. These promising results indicate that polymeric nanoparticles recover the efficacy of imipenem and can be considered as a new paradigm shift against multidrug-resistant isolates in treating severe bacterial infections.

Microspheres for the oral delivery of insulin: preparation, evaluation and hypoglycaemic effect in streptozotocin-induced diabetic rats.

PubMed

Zhang, Huan; Wang, Weimei; Li, Haoran; Peng, Yi; Zhang, Zhiqing

2018-01-01

Insulin-loaded microspheres were prepared by alternating deposition film layers that were composed of insulin and poly(vinyl sulfate) potassium on the surface of poly(lactic acid) (PLA) microspheres. The preparation of the insulin-loaded microspheres was optimized by an orthogonal test design, and the relationship between drug loading (DL) and film layers was studied. The particle size, DL and encapsulation efficiency of the obtained insulin-loaded microspheres with 10 films were 5.25 ± 0.15 µm, 111.33 ± 1.15 mg/g and 33.7 ± 0.19%, respectively. Following this, the physical characteristics of the insulin-loaded microspheres were investigated. The results from scanning electron microscopy and a laser particle size analyzer (LPSA) indicated the spherical morphology, rough surface and increasing particle sizes of the insulin-loaded microspheres, which were compared to those of PLA microspheres. An in vitro release study showed that the insulin-loaded microspheres were stable in HCl solution (pH 1.0) and released insulin slowly in phosphate-buffered solution (pH 6.8). Finally, the drug efficacy of the prepared insulin-loaded microspheres via oral administration was evaluated in rats with diabetes induced by streptozotocin, and an obvious dose-dependent hypoglycemic effect was observed. This preliminary data could illustrate the prospect of using microspheres for the oral delivery of insulin.

Dual stimuli polysaccharide nanovesicles for conjugated and physically loaded doxorubicin delivery in breast cancer cells

NASA Astrophysics Data System (ADS)

Pramod, P. S.; Shah, Ruchira; Jayakannan, Manickam

2015-04-01

The present work reports the development of pH and enzyme dual responsive polysaccharide vesicular nano-scaffolds for the administration of doxorubicin via physical loading and polymer-drug conjugation to breast cancer cells. Dextran was suitably modified with a renewable resource 3-pentadecyl phenol unit through imine and aliphatic ester chemical linkages that acted as pH and esterase enzyme stimuli, respectively. These dual responsive polysaccharide derivatives self-organized into 200 +/- 10 nm diameter nano-vesicles in water. The water soluble anticancer drug doxorubicin (DOX.HCl) was encapsulated in the hydrophilic pocket to produce core-loaded polysaccharide vesicles whereas chemical conjugation produced DOX anchored at the hydrophobic layer of the dextran nano-vesicles. In vitro studies revealed that about 70-80% of the drug was retained under circulatory conditions at pH = 7.4 and 37 °C. At a low pH of 6.0 to 5.0 and in the presence of esterase; both imine and ester linkages were cleaved instantaneously to release 100% of the loaded drugs. Cytotoxicity assays on Wild Type Mouse Embryonic Fibroblasts (WTMEFs) confirmed the non-toxicity of the newly developed dextran derivatives at up to 500 μg mL-1 in PBS. MTT assays on fibroblast cells revealed that DOX.HCl loaded nano-vesicles exhibited better killing abilities than DOX conjugated polymer nano-vesicles. Both DOX loaded and DOX conjugated nano-vesicles were found to show significant killing in breast cancer cells (MCF 7). Confocal microscopy images confirmed the uptake of DOX loaded (or conjugated) nano-vesicles by cells compared to free DOX. Thus, the newly developed pH and enzyme dual responsive polysaccharide vesicular assemblies are potential drug vectors for the administration of DOX in both loaded and chemically conjugated forms for the efficient killing of breast cancer cells.The present work reports the development of pH and enzyme dual responsive polysaccharide vesicular nano-scaffolds for the administration of doxorubicin via physical loading and polymer-drug conjugation to breast cancer cells. Dextran was suitably modified with a renewable resource 3-pentadecyl phenol unit through imine and aliphatic ester chemical linkages that acted as pH and esterase enzyme stimuli, respectively. These dual responsive polysaccharide derivatives self-organized into 200 +/- 10 nm diameter nano-vesicles in water. The water soluble anticancer drug doxorubicin (DOX.HCl) was encapsulated in the hydrophilic pocket to produce core-loaded polysaccharide vesicles whereas chemical conjugation produced DOX anchored at the hydrophobic layer of the dextran nano-vesicles. In vitro studies revealed that about 70-80% of the drug was retained under circulatory conditions at pH = 7.4 and 37 °C. At a low pH of 6.0 to 5.0 and in the presence of esterase; both imine and ester linkages were cleaved instantaneously to release 100% of the loaded drugs. Cytotoxicity assays on Wild Type Mouse Embryonic Fibroblasts (WTMEFs) confirmed the non-toxicity of the newly developed dextran derivatives at up to 500 μg mL-1 in PBS. MTT assays on fibroblast cells revealed that DOX.HCl loaded nano-vesicles exhibited better killing abilities than DOX conjugated polymer nano-vesicles. Both DOX loaded and DOX conjugated nano-vesicles were found to show significant killing in breast cancer cells (MCF 7). Confocal microscopy images confirmed the uptake of DOX loaded (or conjugated) nano-vesicles by cells compared to free DOX. Thus, the newly developed pH and enzyme dual responsive polysaccharide vesicular assemblies are potential drug vectors for the administration of DOX in both loaded and chemically conjugated forms for the efficient killing of breast cancer cells. Electronic supplementary information (ESI) available: 13C NMR of DEX-CHO, 2D NMR spectra of DEX-CHO, 1H NMR of DEX-IM, 1H NMR of DEX-IM-DOX conjugated, absorbance spectra of DEX-IM-DOX conjugated, DLS, FE-SEM and TEM image of DEX-CHO-5, emission spectra of pyrene and Nile red with DEX-IM-10, FE-SEM image of DEX-IM-DOX loaded, FE-SEM image of acid treated DEX-IM-5, absorbance spectra of DOX released, in vitro DOX release from drug loaded and conjugated vesicles in the presence of serum (FBS), DLS data depicting stability of DEX-IM vesicles in serum (FBS), 1HNMR, 13C NMR and HR-MS spectra of all intermediates are provided. See DOI: 10.1039/c5nr00799b

Radiosensitization of paclitaxel, etanidazole and paclitaxel+etanidazole nanoparticles on hypoxic human tumor cells in vitro.

PubMed

Jin, Cheng; Bai, Ling; Wu, Hong; Tian, Furong; Guo, Guozhen

2007-09-01

Paclitaxel and etanidazole are hypoxic radiosensitizers that exhibit cytotoxic action at different mechanisms. The poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel, etanidazole and paclitaxel+etanidazole were prepared by o/w and w/o/w emulsification-solvent evaporation method. The morphology of the nanoparticles was investigated by scanning electron microscope (SEM). The drug encapsulation efficiency (EE) and release profile in vitro were measured by high-performance liquid chromatography (HPLC). The cellular uptake of nanoparticles for the human breast carcinoma cells (MCF-7) and the human carcinoma cervicis cells (HeLa) was evaluated by transmission electronic microscopy and fluorescence microscopy. Cell viability was determined by the ability of single cell to form colonies in vitro. The prepared nanoparticles were spherical shape with size between 80 and 150 nm. The EE was higher for paclitaxel and lower for etanidazole. The drug release was controlled over time. The cellular uptake of nanoparticles was observed. Co-culture of the two tumor cell lines with drug-loaded nanoparticles demonstrated that released drug effectively sensitized hypoxic tumor cells to radiation. The radiosensitization of paclitaxel+etanidazole nanoparticles was more significant than that of single drug-loaded nanoparticles.

Comparative study of DNA encapsulation into PLGA microparticles using modified double emulsion methods and spray drying techniques.

PubMed

Oster, C G; Kissel, T

2005-05-01

Recently, several research groups have shown the potential of microencapsulated DNA as adjuvant for DNA immunization and in tissue engineering approaches. Among techniques generally used for microencapsulation of hydrophilic drug substances into hydrophobic polymers, modified WOW double emulsion method and spray drying of water-in-oil dispersions take a prominent position. The key parameters for optimized microspheres are particle size, encapsulation efficiency, continuous DNA release and stabilization of DNA against enzymatic and mechanical degradation. This study investigates the possibility to encapsulate DNA avoiding shear forces which readily degrade DNA during this microencapsulation. DNA microparticles were prepared with polyethylenimine (PEI) as a complexation agent for DNA. Polycations are capable of stabilizing DNA against enzymatic, as well as mechanical degradation. Further, complexation was hypothesized to facilitate the encapsulation by reducing the size of the macromolecule. This study additionally evaluated the possibility of encapsulating lyophilized DNA and lyophilized DNA/PEI complexes. For this purpose, the spray drying and double emulsion techniques were compared. The size of the microparticles was characterized by laser diffractometry and the particles were visualized by scanning electron microscopy (SEM). DNA encapsulation efficiencies were investigated photometrically after complete hydrolysis of the particles. Finally, the DNA release characteristics from the particles were studied. Particles with a size of <10 microm which represent the threshold for phagocytic uptake could be prepared with these techniques. The encapsulation efficiency ranged from 100-35% for low theoretical DNA loadings. DNA complexation with PEI 25?kDa prior to the encapsulation process reduced the initial burst release of DNA for all techniques used. Spray-dried particles without PEI exhibited high burst releases, whereas double emulsion techniques showed continuous release rates.

Exploration of a Doxorubicin-Polymer Conjugate in Lipid-Polymer Hybrid Nanoparticle Drug Delivery

NASA Astrophysics Data System (ADS)

Lough, Emily

Nanoparticle (NP) drug delivery is a major focus in the research community because of its potential to use existing drugs in safer and more effective ways. Chemotherapy encapsulation in NPs shields the drug from the rest of the body while it is within the NP, with less systemic exposure leading to fewer off-target effects of the drug. However, passive loading of drugs into NPs is a suboptimal method, often leading to burst release upon administration. This work explores the impact of incorporating the drug-polymer conjugate doxorubicin-poly (lactic-co-glycolic) acid (Dox-PLGA) into a lipid-polymer hybrid nanoparticle (LPN). The primary difference in using a drug-polymer conjugate for NP drug delivery is the drug's release kinetics. Dox-PLGA LPNs showed a more sustained and prolonged release profile over 28 days compared to LPNs with passively loaded, unconjugated doxorubicin. This sustained release translates to cytotoxicity; when systemic circulation was simulated using dialysis, Dox-PLGA LPNs retained their cytotoxicity at a higher level than the passively loaded LPNs. The in vivo implication of preserving cytotoxic potency through a slower release profile is that the majority of Dox delivered via Dox-PLGA LPNs will be kept within the LPN until it reaches the tumor. This will result in fewer systemic side effects and more effective treatments given the higher drug concentration at the tumor site. An intriguing clinical application of this drug delivery approach lies in using Dox-PLGA LPNs to cross the blood-brain barrier (BBB). The incorporation of Dox-PLGA is hypothesized to have a protective effect on the BBB as its slow release profile will prevent drug from harming the BBB. Using induced pluripotent stem cells differentiated to human brain microvascular endothelial cells that comprise the BBB, the Dox-PLGA LPNs were shown to be less destructive to the BBB than their passively loaded counterparts. Dox-PLGA LPNs showed superior cytotoxicity against plated tumor cells than the passively loaded Dox LPNs after passing through an in vitro transwell BBB model. Dox-PLGA LPNs and drug-polymer conjugates are exciting alternatives to passively loaded NPs and show strong clinical promise of a treatment that is more potent with fewer side effects and less frequent administration.

Lyophilized silica lipid hybrid (SLH) carriers for poorly water-soluble drugs: physicochemical and in vitro pharmaceutical investigations.

PubMed

Yasmin, Rokhsana; Tan, Angel; Bremmell, Kristen E; Prestidge, Clive A

2014-09-01

Lyophilization was investigated to produce a powdery silica-lipid hybrid (SLH) carrier for oral delivery of poorly water-soluble drugs. The silica to lipid ratio, incorporation of cryoprotectant, and lipid loading level were investigated as performance indicators for lyophilized SLH carriers. Celecoxib, a nonsteroidal anti-inflammatory drug, was used as the model poorly soluble moiety to attain desirable physicochemical and in vitro drug solubilization properties. Scanning electron microscopy and confocal fluorescence imaging verified a nanoporous, homogenous internal matrix structures of the lyophilized SLH particles, prepared from submicron triglyceride emulsions and stabilized by porous silica nanoparticles (Aerosil 380), similar to spray-dried SLH. 20-50 wt % of silica in the formulation have shown to produce nonoily SLH agglomerates with complete lipid encapsulation. The incorporation of a cryoprotectant prevented irreversible aggregation of the silica-stabilized droplets during lyophilization, thereby readily redispersing in water to form micrometre-sized particles (<5 μm). The lyophilized SLH produced approximately 1.5-fold and fivefold increased drug solubilization than the pure drug under nondigesting and digesting conditions, respectively. The feasibility of lyophilization for producing nanostructured SLH formulations with desirable lipid loading and drug solubilization properties for enhanced oral delivery of poorly water-soluble therapeutics is confirmed. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Sulindac loaded alginate beads for a mucoprotective and controlled drug release.

PubMed

Yegin, Betül Arica; Moulari, Brice; Durlu-Kandilci, N Tugba; Korkusuz, Petek; Pellequer, Yann; Lamprecht, Alf

2007-06-01

Ionotropic gelation was used to entrap sulindac into calcium alginate beads as a potential drug carrier for the oral delivery of this anti-inflammatory drug. Beads were investigated in vitro for a possible sustained drug release and their use in vivo as a gastroprotective system for sulindac. Process parameters such as the polymer concentration, polymer/drug ratio, and different needle diameter were analysed for their influences on the bead properties. Size augmented with increasing needle diameter (0.9 mm needle: 1.28 to 1.44 mm; 0.45 mm needle: 1.04 to 1.07 mm) due to changes in droplet size as well as droplet viscosity. Yields varied between 87% and 98% while sulindac encapsulation efficiencies of about 88% and 94% were slightly increasing with higher alginate concentrations. Drug release profiles exhibited a complete release for all formulations within 4 hours with a faster release for smaller beads. Sulindac loaded alginate beads led to a significant reduction of macroscopic histological damage in the stomach and duodenum in mice. Similarly, microscopic analyses of the mucosal damage demonstrated a significant mucoprotective effect of all bead formulation compared to the free drug. The present alginate formulations exhibit promising properties of a controlled release form for sulindac; meanwhile they provide a distinct tissue protection in the stomach and duodenum.

Bioinspired Ultratough Hydrogel with Fast Recovery, Self-Healing, Injectability and Cytocompatibility.

PubMed

Azevedo, Sara; Costa, Ana M S; Andersen, Amanda; Choi, Insung S; Birkedal, Henrik; Mano, João F

2017-07-01

Inspired by the mussel byssus adhesiveness, a highly hydrated polymeric structure is designed to combine, for the first time, a set of interesting features for load-bearing purposes. These characteristics include: i) a compressive strength and stiffness in the MPa range, ii) toughness and the ability to recover it upon successive cyclic loading, iii) the ability to quickly self-heal upon rupture, iv) the possibility of administration through minimally invasive techniques, such as by injection, v) the swelling ratio being adjusted to space-filling applications, and vi) cytocompatibility. Owing to these characteristics and the mild conditions employed, the encapsulation of very unstable and sensitive cargoes is possible, highlighting their potential to researchers in the biomedical field for the repair of load-bearing soft tissues, or to be used as an encapsulation platform for a variety of biological applications such as disease models for drug screening and therapies in a more realistic mechanical environment. Moreover, given the simplicity of this methodology and the enhanced mechanical performance, this strategy can be expanded to applications in other fields, such as agriculture and electronics. As such, it is anticipated that the proposed strategy will constitute a new, versatile, and cost-effective tool to produce engineered polymeric structures for both science and technology. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Post-insertion of poloxamer 188 strengthened liposomal membrane and reduced drug irritancy and in vivo precipitation, superior to PEGylation.

PubMed

Zhang, Wenli; Wang, Guangji; See, Esther; Shaw, John P; Baguley, Bruce C; Liu, Jianping; Amirapu, Satya; Wu, Zimei

2015-04-10

The ultimate aim of this study was to develop asulacrine (ASL)-loaded long-circulating liposomes to prevent phlebitis during intravenous (i.v.) infusion for chemotherapy. Poly(ethylene)glycol (PEG) and poloxamer 188-modified liposomes (ASL-PEGL and ASL-P188L) were developed, and ASL was loaded using a remote loading method facilitated with a low concentration of sulfobutyl ether-β-cyclodextrin as a drug solubilizer. The liposomes were characterized in terms of morphology, size, release properties and stability. Pharmacokinetics and venous tissue tolerance of the formulations were simultaneously studied in rabbits following one-hour i.v. infusion via the ear vein. The irritancy was assessed using a rat paw-lift/lick model after subplantar injections. High drug loading 9.0% w/w was achieved with no drug leakage found from ASL-PEGL or ASL-P188L suspended in a 5% glucose solution at 30days. However, a rapid release (leakage) from ASL-PEGL was observed when PBS was used as release medium, partially related to the use of cyclodextrin in drug loading. Post-insertion of poloxamer 188 to the liposomes appeared to be able to restore the drug retention possibly by increasing the packing density of phospholipids in the membrane. In rabbits (n=5), ASL-P188L had a prolonged half-life with no drug precipitation or inflammation in the rabbit ear vein in contrast to ASL solution. Following subplantar (footpad) injections in rats ASL solution induced paw-lick/lift responses in all rats whereas ASL-P188L caused no response (n=8). PEGylation showed less benefit possibly due to the drug 'leakage'. In conclusion, drug precipitation in the vein and the drug mild irritancy may both contribute to the occurrence of phlebitis caused by the ASL solution, and could both be prevented by encapsulation of the drug in liposomes. Poloxamer 188 appeared to be able to 'seal' the liposomal membrane and enhance drug retention. The study also highlighted the importance of bio-relevant in vitro release study in formulation screening. Copyright © 2015. Published by Elsevier B.V.

A novel self-assembled nanoparticle platform based on pectin-eight-arm polyethylene glycol-drug conjugates for co-delivery of anticancer drugs.

PubMed

Liu, Yanxue; Liu, Kefeng; Li, Xiaomin; Xiao, Shangzhen; Zheng, Dan; Zhu, Pengbo; Li, Chunxiao; Liu, Jing; He, Jing; Lei, Jiandu; Wang, Luying

2018-05-01

The application of non-toxic carriers to increase drug loading, multi-drug delivery, and extremely small size of nano-drugs to construct a tremendous transmission system is the goal for all researchers to be pursued. The proposal of natural pectin nano-platform for delivery of multiple drugs is critical for biomedical research, especially a particle size of below 100nm with high yield. Here we design a new core-shell structure pectin-eight-arm polyethylene glycol-ursolic acid/hydrooxycampothecin nanoparticle (Pec-8PUH NPs) through a special self-assembly method for stabilizing and dispersing particles, improving water-solubility, and achieving drug controlled release. The obtained Pec-8PUH NPs possessed appropriate size (~91nm), drug-loaded efficiency and encapsulation efficiency through the regulation of eight-arm polyethylene glycol. In addition, Pec-8PUH NPs could enhance cell cytotoxicity, shorten blood retention time (7.3-fold UA, 7.2-fold HCPT) and more effective cellular uptake than free drugs, which exhibited an obvious synergistic effect of UA and HCPT by the co-delivery. 4T1 tumor-bearing mice also showed a higher survival rate than free UA and free HCPT. The result further shows that this novel drug delivery system has a promising potential for anti-cancer combination therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled release of beta-estradiol from PLAGA microparticles: the effect of organic phase solvent on encapsulation and release.

PubMed

Birnbaum, D T; Kosmala, J D; Henthorn, D B; Brannon-Peppas, L

2000-04-03

To determine the effect of the organic solvent used during microparticle preparation on the in vitro release of beta-estradiol, a number of formulations were evaluated in terms of size, shape and drug delivery performance. Biodegradable microparticles of poly(lactide-co-glycolide) were prepared containing beta-estradiol that utilized dichloromethane, ethyl acetate or a mixture of dichloromethane and methanol as the organic phase solvent during the particle preparation. The drug delivery behavior from the microparticles was studied and comparisons were made of their physical properties for different formulations. The varying solubilities of beta-estradiol and poly(lactide-co-glycolide) in the solvents studied resulted in biodegradable microparticles with very different physical characteristics. Microparticles prepared from solid suspensions of beta-estradiol using dichloromethane as the organic phase solvent were similar in appearance to microparticles prepared without drug. Microparticles prepared from dichloromethane/methanol solutions appeared transparent to translucent depending on the initial amount of drug used in the formulation. Microparticles prepared using ethyl acetate appeared to have the most homogeneous encapsulation of beta-estradiol, appearing as solid white spheres regardless of initial drug content. Studies showed that microparticles prepared from either ethyl acetate or a mixture of dichloromethane and methanol gave a more constant release profile of beta-estradiol than particles prepared using dichloromethane alone. For all formulations, an initial burst of release increased with increasing drug loading, regardless of the organic solvent used.

Creatinine-based non-phospholipid vesicular carrier for improved oral bioavailability of Azithromycin.

PubMed

Ullah, Shafi; Shah, Muhammad Raza; Shoaib, Mohammad; Imran, Muhammad; Shah, Syed Wadood Ali; Ali, Imdad; Ahmed, Farid

2017-06-01

Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs. This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability. Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug-excipient interaction using zetasizer, atomic force microscope (AFM), LC-MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits. The vesicles were spherical with 247 ± 4.67 nm diameter hosting 73.29 ± 3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80 ± 0.51% hemolysis at 1000 µg/mL. It was also found safe in mice up to 2.5 g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits. The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.