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Sample records for acid plga nanoparticles

  1. Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil.

    PubMed

    Yadav, Awesh K; Agarwal, Abhinav; Rai, Gopal; Mishra, Pradeep; Jain, Sanyog; Mishra, Anil K; Agrawal, Himanshu; Agrawal, Govind P

    2010-11-01

    The present investigation was aimed to develop and explore the prospective of engineered PLGA nanoparticles as vehicles for targeted delivery of 5-fluorouracil (5-FU). Nanoparticles of 5-FU-loaded hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA-FU) copolymer were prepared and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, DSC, and X-ray diffractometer measurement studies. The nanoparticulate formulation was evaluated for in vitro release, hemolytic toxicity, and hematological toxicity. Cytotoxicity studies were performed on Ehrlich ascites tumor (EAT) cell lines using MTT cell proliferation assay. Biodistribution studies of 99m Tc labeled formulation were conducted on EAT-bearing mice. The in vivo tumor inhibition study was also performed after i.v. administration of HA-PEG-PLGA-FU nanoparticles. The HA conjugated formulation was found to be less hemolytic but more cytotoxic as compared to free drug. The hematological data suggested that HA-PEG-PLGA-FU formulation was less immunogenic compared to plain drug. The tissue distribution studies displayed that HA-PEG-PLGA-FU were able to deliver a higher concentration of 5-FU in the tumor mass. In addition, the HA-PEG-PLGA-FU nanoparticles reduced tumor volume significantly in comparison with 5-FU. Thus, it was concluded that the conjugation of HA imparts targetability to the formulation, and enhanced permeation and retention effect ruled out its access to the non-tumor tissues, at the same time favored selective entry in tumors, thereby reducing the side-effects both in vitro and in vivo.

  2. Novel Simvastatin-Loaded Nanoparticles Based on Cholic Acid-Core Star-Shaped PLGA for Breast Cancer Treatment.

    PubMed

    Wu, Yanping; Wang, Zhongyuan; Liu, Gan; Zeng, Xiaowei; Wang, Xusheng; Gao, Yongfeng; Jiang, Lijuan; Shi, Xiaojun; Tao, Wei; Huang, Laiqiang; Mei, Lin

    2015-07-01

    A novel nanocarrier system of cholic acid (CA) core, star-shaped polymer consisting of poly(D,L-lactide-co-glycolide) (PLGA) was developed for sustained and controlled delivery of simvastatin for chemotherapy of breast adenocarcinoma. The star-shaped polymer CA-PLGA with three branch arms was synthesized successfully through the core-first approach. The simvastatin-loaded star-shaped CA-PLGA nanoparticles were prepared through a modified nanoprecipitation method. The data showed that the fluorescence star-shaped CA-PLGA nanoparticles could be internalized into MDA-MB-231 and MDA-MB-468 human breast cancer cells. The simvastatin-loaded star-shaped CA-PLGA nanoparticles achieved significantly higher level of cytotoxicity than pristine simvastatin and simvastatin-loaded linear PLGA nanoparticles. Moreover, the expression of the cell cycle protein cyclin D1 was dramatically inhibited by simvastatin in both cells, with simvastatin-loaded star-shaped CA-PLGA nanoparticles having the greatest effect. MDA-MB-231 xenograft tumor model on BALB/c nude mice showed that simvastatin-loaded star-shaped CA-PLGA nanoformulations could effectively inhibit the growth of tumor over a longer period of time than pristine simvastatin and simvastatin-loaded linear PLGA nanoformulations at the same dose. In agreement with these, the nuclear expression of proliferation marker Ki-67 in simvastatin-loaded star-shaped CA-PLGA nanoparticles group was reduced to a most extent among four groups through tumor frozen section immunohistochemistry. In conclusion, the star-shaped CA-PLGA polymers could serve as a novel polymeric nanocarrier for breast cancer chemotherapy.

  3. Spontaneous arrangement of a tumor targeting hyaluronic acid shell on irinotecan loaded PLGA nanoparticles.

    PubMed

    Giarra, Simona; Serri, Carla; Russo, Luisa; Zeppetelli, Stefania; De Rosa, Giuseppe; Borzacchiello, Assunta; Biondi, Marco; Ambrosio, Luigi; Mayol, Laura

    2016-04-20

    The arrangement of tumor targeting hyaluronic acid (HA) moieties on irinotecan (IRIN)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) has been directed by means of a gradient of lipophilicity between the oil and water phases of the emulsion used to produce the NPs. PLGA constitutes the NP bulk while HA is superficially exposed, with amphiphilic poloxamers acting as a bridge between PLGA and HA. Differential scanning calorimetry, zeta potential analyses and ELISA tests were employed to support the hypothesis of polymer assembly in NP formulations. The presence of flexible HA chains on NP surface enhances NP size stability over time due to an increased electrostatic repulsion between NPs and a higher degree of hydration of the device surface. IRIN in vitro release kinetics can be sustained up to 7-13 days. In vitro biologic studies indicated that HA-containing NPs were more toxic than bare PLGA NPs against CD44-overexpressing breast carcinoma cells (HS578T), therefore indicating their ability to target CD44 receptor.

  4. New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB) Stabilized Poly(Lactic-co-Glycolic Acid) (PLGA) Nanoparticles

    PubMed Central

    Gossmann, Rebecca; Langer, Klaus; Mulac, Dennis

    2015-01-01

    Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB), in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA) and polyethylene glycol (PEG) modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to a lower

  5. Cellular uptake, antioxidant and antiproliferative activity of entrapped α-tocopherol and γ-tocotrienol in poly (lactic-co-glycolic) acid (PLGA) and chitosan covered PLGA nanoparticles (PLGA-Chi).

    PubMed

    Alqahtani, Saeed; Simon, Lacey; Astete, Carlos E; Alayoubi, Alaadin; Sylvester, Paul W; Nazzal, Sami; Shen, Yixiao; Xu, Zhimin; Kaddoumi, Amal; Sabliov, Cristina M

    2015-05-01

    The aim of this study was to formulate and characterize α-tocopherol (α-T) and tocotrienol-rich fraction (TRF) entrapped in poly (lactide-co-glycolide) (PLGA) and chitosan covered PLGA (PLGA-Chi) based nanoparticles. The resultant nanoparticles were characterized and the effect of nanoparticles entrapment on the cellular uptake, antioxidant, and antiproliferative activity of α-T and TRF were tested. In vitro uptake studies in Caco2 cells showed that PLGA and PLGA-Chi nanoparticles displayed a greater enhancement in the cellular uptake of α-T and TRF when compared with the control without causing toxicity to the cells (p<0.0001). Furthermore, the cellular internalization of both PLGA and PLGA-Chi nanoparticles labeled with FITC was investigated by fluorescence microscopy; both types of nanoparticles were able to get internalized into the cells with reasonable amounts. However, PLGA-Chi nanoparticles showed significantly higher (3.5-fold) cellular uptake compared to PLGA nanoparticles. The antioxidant activity studies demonstrated that entrapment of α-T and TRF in PLGA and PLGA-Chi nanoparticles exhibited greater ability in inhibiting cholesterol oxidation at 48 h compared to the control. In vitro antiproliferative studies confirmed marked cytotoxicity of TRF on MCF-7 and MDA-MB-231 cell lines when delivered by PLGA and PLGA-Chi nanoparticles after 48 h incubation compared to control. In summary, PLGA and PLGA-Chi nanoparticles may be considered as an attractive and promising approach to enhance the bioavailability and activity of poorly water soluble compounds such as α-tocopherol and tocotrienols.

  6. Electrospun aligned PLGA and PLGA/gelatin nanofibers embedded with silica nanoparticles for tissue engineering.

    PubMed

    Mehrasa, Mohammad; Asadollahi, Mohammad Ali; Ghaedi, Kamran; Salehi, Hossein; Arpanaei, Ayyoob

    2015-08-01

    Aligned poly lactic-co-glycolic acid (PLGA) and PLGA/gelatin nanofibrous scaffolds embedded with mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. The mean diameters of nanofibers were 641±24 nm for the pure PLGA scaffolds vs 418±85 nm and 267±58 nm for the PLGA/10 wt% MSNPs and the PLGA/gelatin/10 wt% MSNPs scaffolds, respectively. The contact angle measurement results (102°±6.7 for the pure PLGA scaffold vs 81°±6.8 and 18°±8.7 for the PLGA/10 wt% MSNPs and the PLGA/gelatin/10 wt% MSNPs scaffolds, respectively) revealed enhanced hydrophilicity of scaffolds upon incorporation of gelatin and MSNPs. Besides, embedding the scaffolds with MSNPs resulted in improved tensile mechanical properties. Cultivation of PC12 cells on the scaffolds demonstrated that introduction of MSNPs into PLGA and PLGA/gelatin matrices leads to the improved cell attachment and proliferation as well as long cellular processes. DAPI staining results indicated that cell proliferations on the PLGA/10 wt% MSNPs and the PLGA/gelatin/10 wt% MSNPs scaffolds were strikingly (nearly 2.5 and 3 folds, respectively) higher than that on the aligned pure PLGA scaffolds. These results suggest superior properties of silica nanoparticles-incorporated PLGA/gelatin eletrospun nanofibrous scaffolds for the stem cell culture and tissue engineering applications.

  7. Hyaluronic acid grafted PLGA copolymer nanoparticles enhance the targeted delivery of Bromelain in Ehrlich's Ascites Carcinoma.

    PubMed

    Bhatnagar, Priyanka; Pant, Aditya Bhushan; Shukla, Yogeshwer; Panda, Amulya; Gupta, Kailash Chand

    2016-08-01

    Rapidly increasing malignant neoplastic disease demands immediate attention. Several dietary compounds have recently emerged as strong anti-cancerous agents. Among, Bromelain (BL), a protease from pineapple plant, was used to enhance its anti-cancerous efficacy using nanotechnology. In lieu of this, hyaluronic acid (HA) grafted PLGA copolymer, having tumor targeting ability, was developed. BL was encapsulated in copolymer to obtain BL-copolymer nanoparticles (NPs) that ranged between 140 to 281nm in size. NPs exhibited higher cellular uptake and cytotoxicity in cells with high CD44 expression as compared with non-targeted NPs. In vivo results on tumor bearing mice showed that NPs were efficient in suppressing the tumor growth. Hence, the formulation could be used as a self-targeting drug delivery cargo for the remission of cancer.

  8. 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.

  9. Aspartic acid-based modified PLGA-PEG nanoparticles for bone targeting: in vitro and in vivo evaluation.

    PubMed

    Fu, Yin-Chih; Fu, Tzu-Fun; Wang, Hung-Jen; Lin, Che-Wei; Lee, Gang-Hui; Wu, Shun-Cheng; Wang, Chih-Kuang

    2014-11-01

    Nanoparticles (NP) that target bone tissue were developed using PLGA-PEG (poly(lactic-co-glycolic acid)-polyethylene glycol) diblock copolymers and bone-targeting moieties based on aspartic acid, (Asp)(n(1,3)). These NP are expected to enable the transport of hydrophobic drugs. The molecular structures were examined by (1)H NMR or identified using mass spectrometry and Fourier transform infrared (FT-IR) spectra. The NP were prepared using the water miscible solvent displacement method, and their size characteristics were evaluated using transmission electron microscopy (TEM) and dynamic light scattering. The bone targeting potential of the NP was evaluated in vitro using hydroxyapatite affinity assays and in vivo using fluorescent imaging in zebrafish and rats. It was confirmed that the average particle size of the NP was <200 nm and that the dendritic Asp3 moiety of the PLGA-PEG-Asp3 NP exhibited the best apatite mineral binding ability. Preliminary findings in vivo bone affinity assays in zebrafish and rats indicated that the PLGA-PEG-ASP3 NP may display increased bone-targeting efficiency compared with other PLGA-PEG-based NP that lack a dendritic Asp3 moiety. These NP may act as a delivery system for hydrophobic drugs, warranting further evaluation of the treatment of bone disease.

  10. Highly Stable PEGylated Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles for the Effective Delivery of Docetaxel in Prostate Cancers

    NASA Astrophysics Data System (ADS)

    Cao, Long-Bin; Zeng, Sha; Zhao, Wei

    2016-06-01

    In the present study, a highly stable luteinizing-hormone-releasing hormone (LHRH)-conjugated PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles were developed for the successful treatment of prostate cancers. We have demonstrated that a unique combination of targeted drug delivery and controlled drug release is effective against prostate cancer therapy. The docetaxel (DTX)/PLGA-LHRH micelles possessed a uniform spherical shape with an average diameter of ~170 nm. The micelles exhibited a controlled drug release for up to 96 h which can minimize the non-specific systemic spread of toxic drugs during circulation while maximizing the efficiency of tumor-targeted drug delivery. The LHRH-conjugated micelles showed enhanced cellular uptake and exhibited significantly higher cytotoxicity against LNCaP cancer cells. We have showed that PLGA-LHRH induced greater caspase-3 activity indicating its superior apoptosis potential. Consistently, LHRH-conjugated micelles induced threefold and twofold higher G2/M phase arrest than compared to free DTX or PLGA NP-treated groups. Overall, results indicate that use of LHRH-conjugated nanocarriers may potentially be an effective nanocarrier to effectively treat prostate cancer.

  11. Tailoring magnetic PLGA nanoparticles suitable for doxorubicin delivery

    NASA Astrophysics Data System (ADS)

    Tansık, Gülistan; Yakar, Arzu; Gündüz, Ufuk

    2014-01-01

    One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells, which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale-based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an external magnetic field. Thus, the drug can be carried to the targeted site safely. The aim of this study is to prepare poly( dl-lactic- co-glycolic acid) (PLGA)-coated magnetic nanoparticles and load anti-cancer drug, doxorubicin to them. For this purpose, magnetite (Fe3O4) iron oxide nanoparticles were synthesized as a magnetic core material (MNP) and then coated with oleic acid. Oleic acid-coated MNP (OA-MNP) was encapsulated into PLGA. Effects of different OA-MNP/PLGA ratios on magnetite entrapment efficiency were investigated. Doxorubicin-loaded magnetic polymeric nanoparticles (DOX-PLGA-MNP) were prepared. After the characterization of prepared nanoparticles, their cytotoxic effects on MCF-7 cell line were studied. PLGA-coated magnetic nanoparticles (PLGA-MNP) had a proper size and superparamagnetic character. The highest magnetite entrapment efficiency of PLGA-MNP was estimated as 63 % at 1:8 ratio. Cytotoxicity studies of PLGA-MNP did not indicate any notable cell death between the concentration ranges of 2 and 125 μg/ml. Drug loading efficiency was estimated as 32 %, and it was observed that DOX-PLGA-MNP showed significant cytotoxicity on MCF-7 cells compared to PLGA-MNP. The results showed that prepared nanoparticles have desired size and superparamagnetic characteristics without serious toxic effects on cells. These nanoparticles may be suitable for targeted drug delivery applications.

  12. Acid-Sensitive Sheddable PEGylated PLGA Nanoparticles Increase the Delivery of TNF-α siRNA in Chronic Inflammation Sites

    PubMed Central

    Aldayel, Abdulaziz M; Naguib, Youssef W; O'Mary, Hannah L; Li, Xu; Niu, Mengmeng; Ruwona, Tinashe B; Cui, Zhengrong

    2016-01-01

    There has been growing interest in utilizing small interfering RNA (siRNA) specific to pro-inflammatory cytokines, such as tumor necrosis factor-α ( TNF-α), in chronic inflammation therapy. However, delivery systems that can increase the distribution of the siRNA in chronic inflammation sites after intravenous administration are needed. Herein we report that innovative functionalization of the surface of siRNA-incorporated poly (lactic-co-glycolic) acid (PLGA) nanoparticles significantly increases the delivery of the siRNA in the chronic inflammation sites in a mouse model. The TNF-α siRNA incorporated PLGA nanoparticles were prepared by the standard double emulsion method, but using stearoyl-hydrazone-polyethylene glycol 2000, a unique acid-sensitive surface active agent, as the emulsifying agent, which renders (i) the nanoparticles PEGylated and (ii) the PEGylation sheddable in low pH environment such as that in chronic inflammation sites. In a mouse model of lipopolysaccharide-induced chronic inflammation, the acid-sensitive sheddable PEGylated PLGA nanoparticles showed significantly higher accumulation or distribution in chronic inflammation sites than PLGA nanoparticles prepared with an acid-insensitive emulsifying agent (i.e., stearoyl-amide-polyethylene glycol 2000) and significantly increased the distribution of the TNF-α siRNA incorporated into the nanoparticles in inflamed mouse foot. PMID:27434685

  13. Multifunctional PLGA particles containing poly(l-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity.

    PubMed

    Stevanović, Magdalena; Bračko, Ines; Milenković, Marina; Filipović, Nenad; Nunić, Jana; Filipič, Metka; Uskoković, Dragan P

    2014-01-01

    A water-soluble antioxidant (ascorbic acid, vitamin C) was encapsulated together with poly(l-glutamic acid)-capped silver nanoparticles (AgNpPGA) within a poly(lactide-co-glycolide) (PLGA) polymeric matrix and their synergistic effects were studied. The PLGA/AgNpPGA/ascorbic acid particles synthesized by a physicochemical method with solvent/non-solvent systems are spherical, have a mean diameter of 775 nm and a narrow size distribution with a polydispersity index of 0.158. The encapsulation efficiency of AgNpPGA/ascorbic acid within PLGA was determined to be >90%. The entire amount of encapsulated ascorbic acid was released in 68 days, and the entire amount of AgNpPGAs was released in 87 days of degradation. The influence of PLGA/AgNpPGA/ascorbic acid on cell viability, generation of reactive oxygen species (ROS) in HepG2 cells, as well as antimicrobial activity against seven different pathogens was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated good biocompatibility of these PLGA/AgNpPGA/ascorbic acid particles. We measured the kinetics of ROS formation in HepG2 cells by a DCFH-DA assay, and found that PLGA/AgNpPGA/ascorbic acid caused a significant decrease in DCF fluorescence intensity, which was 2-fold lower than that in control cells after a 5h exposure. This indicates that the PLGA/AgNpPGA/ascorbic acid microspheres either act as scavengers of intracellular ROS and/or reduce their formation. Also, the results of antimicrobial activity of PLGA/AgNpPGA/ascorbic acid obtained by the broth microdilution method showed superior and extended activity of these particles. The samples were characterized using Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, zeta potential and particle size analysis. This paper presents a new approach to the treatment of infection that at the same time offers a very pronounced antioxidant effect.

  14. Synthesis and characterization of magnetite/PLGA/chitosan nanoparticles

    NASA Astrophysics Data System (ADS)

    Ibarra, Jaime; Melendres, Julio; Almada, Mario; Burboa, María G.; Taboada, Pablo; Juárez, Josué; Valdez, Miguel A.

    2015-09-01

    In this work, we report the synthesis and characterization of a new hybrid nanoparticles system performed by magnetite nanoparticles, loaded in a PLGA matrix, and stabilized by different concentrations of chitosan. Magnetite nanoparticles were hydrophobized with oleic acid and entrapped in a PLGA matrix by the emulsion solvent evaporation method, after that, magnetite/PLGA/chitosan nanoparticles were obtained by adding dropwise magnetite/PLGA nanoparticles in chitosan solutions. Magnetite/PLGA nanoparticles produced with different molar ratios did not show significant differences in size and the 3:1 molar ratio showed best spherical shapes as well as uniform particle size. Isothermal titration calorimetry studies demonstrated that the first stage of PLGA-chitosan interaction is mostly regulated by electrostatic forces. Based on a single set of identical sites model, we obtained for the average number of binding sites a value of 3.4, which can be considered as the number of chitosan chains per nanoparticle. This value was confirmed by using a model based on the DLVO theory and fitting zeta potential measurements of magnetite/PLGA/chitosan nanoparticles. From the adjusted parameters, we found that an average number of chitosan molecules of 3.6 per nanoparticle are attached onto the surface of the PLGA matrix. Finally, we evaluated the effect of surface charge of nanoparticles on a membrane model of endothelial cells performed by a mixture of three phospholipids at the air-water interface. Different isotherms and adsorption curves show that cationic surface of charged nanoparticles strongly interact with the phospholipids mixture and these results can be the basis of future experiments to understand the nanoparticles- cell membrane interaction.

  15. Lectin-Conjugated Clarithromycin and Acetohydroxamic Acid-Loaded PLGA Nanoparticles: a Novel Approach for Effective Treatment of H. pylori.

    PubMed

    Jain, Sunil K; Haider, Tanweer; Kumar, Amrish; Jain, Akhlesh

    2016-10-01

    Helicobacter pylori infection remains challenging as it mainly colonized beneath the deep gastric mucosa and adheres to epithelial cells of the stomach. Concanavalin-A (Con-A)-conjugated gastro-retentive poly (lactic-co-glycolic acid) (PLGA) nanoparticles of acetohydroxamic acid (AHA) and clarithromycin (CLR) were prepared and evaluated under in vitro conditions. Solvent evaporation method was employed for preparation of nanoparticles and characterized for particle size distribution, surface morphology, percent drug entrapment, and in vitro drug release in simulated gastric fluid. Optimized nanoparticles were conjugated with Con-A and further characterized for Con-A conjugation efficiency and mucoadhesion and tested for in vitro anti-H. pylori activity. The conjugation with Con-A further sustained the drug release over a period of 8 h when compared to non-conjugated nanoparticles of AHA and CLR. In vitro anti H. pylori study confirmed that Con-A-conjugated nanoparticles containing both drugs, i.e., CLR and AHA, had shown maximum zone of inhibition compared to other formulations. In a nut shell, results suggest that the developed systems could be used for better therapeutic activity against H. pylori infection.

  16. Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis.

    PubMed

    Lin, Ts-Ting; Gao, Dong-Yu; Liu, Ya-Chi; Sung, Yun-Chieh; Wan, Dehui; Liu, Jia-Yu; Chiang, Tsaiyu; Wang, Liying; Chen, Yunching

    2016-01-10

    Sorafenib is a tyrosine kinase inhibitor that has recently been shown to be a potential antifibrotic agent. However, a narrow therapeutic window limits the clinical use and therapeutic efficacy of sorafenib. Herein, we have developed and optimized nanoparticle (NP) formulations prepared from a mixture of poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers with poly(lactic-co-glycolic acid) (PLGA) for the systemic delivery of sorafenib into the fibrotic livers of CCl4-induced fibrosis mouse models. We characterized and compared the pharmaceutical and biological properties of two different PLGA nanoparticles (NPs)--PEG-PLGA NPs (PEG-PLGA/PLGA=10/0) and PEG-PLGA/PLGA NPs (PEG-PLGA/PLGA=5/5). Increasing the PLGA content in the PEG-PLGA/PLGA mixture led to increases in the particle size and drug encapsulation efficacy and a decrease in the drug release rate. Both PEG-PLGA and PEG-PLGA/PLGA NPs significantly prolonged the blood circulation of the cargo and increased the uptake by the fibrotic livers. The systemic administration of PEG-PLGA or PEG-PLGA/PLGA NPs containing sorafenib twice per week for a period of 4 weeks efficiently ameliorated liver fibrosis, as indicated by decreased α-smooth muscle actin (α-SMA) content and collagen production in the livers of CCl4-treated mice. Furthermore, sorafenib-loaded PLGA NPs significantly shrank the abnormal blood vessels and decreased microvascular density (MVD), leading to vessel normalization in the fibrotic livers. In conclusion, our results reflect the clinical potential of sorafenib-loaded PLGA NPs for the prevention and treatment of liver fibrosis.

  17. Comparative evaluation of antibacterial activity of caffeic acid phenethyl ester and PLGA nanoparticle formulation by different methods

    NASA Astrophysics Data System (ADS)

    Arasoglu, Tülin; Derman, Serap; Mansuroglu, Banu

    2016-01-01

    The aim of the present study was to evaluate the antimicrobial activity of nanoparticle and free formulations of the CAPE compound using different methods and comparing the results in the literature for the first time. In parallel with this purpose, encapsulation of CAPE with the PLGA nanoparticle system (CAPE-PLGA-NPs) and characterization of nanoparticles were carried out. Afterwards, antimicrobial activity of free CAPE and CAPE-PLGA-NPs was determined using agar well diffusion, disk diffusion, broth microdilution and reduction percentage methods. P. aeroginosa, E. coli, S. aureus and methicillin-resistant S. aureus (MRSA) were chosen as model bacteria since they have different cell wall structures. CAPE-PLGA-NPs within the range of 214.0 ± 8.80 nm particle size and with an encapsulation efficiency of 91.59 ± 4.97% were prepared using the oil-in-water (o-w) single-emulsion solvent evaporation method. The microbiological results indicated that free CAPE did not have any antimicrobial activity in any of the applied methods whereas CAPE-PLGA-NPs had significant antimicrobial activity in both broth dilution and reduction percentage methods. CAPE-PLGA-NPs showed moderate antimicrobial activity against S. aureus and MRSA strains particularly in hourly measurements at 30.63 and 61.25 μg ml-1 concentrations (both p < 0.05), whereas they failed to show antimicrobial activity against Gram-negative bacteria (P. aeroginosa and E. coli, p > 0.05). In the reduction percentage method, in which the highest results of antimicrobial activity were obtained, it was observed that the antimicrobial effect on S. aureus was more long-standing (3 days) and higher in reduction percentage (over 90%). The appearance of antibacterial activity of CAPE-PLGA-NPs may be related to higher penetration into cells due to low solubility of free CAPE in the aqueous medium. Additionally, the biocompatible and biodegradable PLGA nanoparticles could be an alternative to solvents such as ethanol

  18. Comparative evaluation of antibacterial activity of caffeic acid phenethyl ester and PLGA nanoparticle formulation by different methods.

    PubMed

    Arasoglu, Tülin; Derman, Serap; Mansuroglu, Banu

    2016-01-15

    The aim of the present study was to evaluate the antimicrobial activity of nanoparticle and free formulations of the CAPE compound using different methods and comparing the results in the literature for the first time. In parallel with this purpose, encapsulation of CAPE with the PLGA nanoparticle system (CAPE-PLGA-NPs) and characterization of nanoparticles were carried out. Afterwards, antimicrobial activity of free CAPE and CAPE-PLGA-NPs was determined using agar well diffusion, disk diffusion, broth microdilution and reduction percentage methods. P. aeroginosa, E. coli, S. aureus and methicillin-resistant S. aureus (MRSA) were chosen as model bacteria since they have different cell wall structures. CAPE-PLGA-NPs within the range of 214.0 ± 8.80 nm particle size and with an encapsulation efficiency of 91.59 ± 4.97% were prepared using the oil-in-water (o-w) single-emulsion solvent evaporation method. The microbiological results indicated that free CAPE did not have any antimicrobial activity in any of the applied methods whereas CAPE-PLGA-NPs had significant antimicrobial activity in both broth dilution and reduction percentage methods. CAPE-PLGA-NPs showed moderate antimicrobial activity against S. aureus and MRSA strains particularly in hourly measurements at 30.63 and 61.25 μg ml(-1) concentrations (both p < 0.05), whereas they failed to show antimicrobial activity against Gram-negative bacteria (P. aeroginosa and E. coli, p > 0.05). In the reduction percentage method, in which the highest results of antimicrobial activity were obtained, it was observed that the antimicrobial effect on S. aureus was more long-standing (3 days) and higher in reduction percentage (over 90%). The appearance of antibacterial activity of CAPE-PLGA-NPs may be related to higher penetration into cells due to low solubility of free CAPE in the aqueous medium. Additionally, the biocompatible and biodegradable PLGA nanoparticles could be an alternative to solvents such as ethanol

  19. Immune activity and biodistribution of polypeptide K237 and folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles radiolabeled with 99mTc

    PubMed Central

    Wu, Yufeng; Huang, Xuanzhang; Chen, Jie; Xia, Junyong; Jiang, Hao; Ma, Jing; Wu, Jian

    2016-01-01

    In a previous study, amphiphilic copolymer, polypeptide K237 (HTMYYHHYQHHL) and folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (K237/FA-PEG-PLGA) nanoparticles were developed and studied as a drug carrier. To further promote the clinical application of K237/FA-PEG-PLGA nanoparticles and provide guidance for future research, we need to examine their specific biodistribution in vivo. In this study, K237/FA-PEG-PLGA nanoparticles were effectively labeled by a direct method with Technetium-99m (99mTc) using stannous chloride as a reducing agent. The optimal stability of the labeled nanoparticles was determined by evaluating their radiochemical purity in serum, physiological saline, diethylenetriaminepentaacetic acid (DTPA) and cysteine solutions. The affinity of ligands and receptors was elicited by cell binding and blocking experiments in KDR/folate receptor high expressing SKOV-3 ovarian cancer cells. The nanoparticles biodistribution was studied after intravenous administration in healthy mice xenografted with SKOV-3 cells. A higher percent injected dose per gram of tissue (% ID/g) was observed in liver, kidney, spleen, blood and tumor at 3 and 9 h post-injection. Scintigraphic images revealed that the radioactivity was mainly concentrated in tumor, liver, kidney and bladder; and in the heart, lung, and muscle was significantly lower at 3 h. The radioactivity distribution in the images is consistent with the in vivo biodistribution data. Our works demonstrated that K237/FA-PEG-PLGA nanoparticles have great potential as biodegradable drug carriers, especially for tumors expressing the folate and KDr receptor. PMID:27791199

  20. Biodistribution of PLGA and PLGA/chitosan nanoparticles after repeat-dose oral delivery in F344 rats for 7 days

    PubMed Central

    Navarro, Sara M; Darensbourg, Caleb; Cross, Linda; Stout, Rhett; Coulon, Diana; Astete, Carlos E; Morgan, Timothy; Sabliov, Cristina M

    2015-01-01

    Aim To quantify in vivo the biodistribution of poly(lactic-co-glycolic) acid (PLGA) and PLGA/chitosan nanoparticles (PLGA/Chi NPs) and assess if the positive charge of chitosan significantly enhances nanoparticle absorption in the GI tract. Material & methods PLGA and PLGA/Chi NPs covalently linked to tetramethylrhodamine-5-isothiocyanate (TRITC) were orally administered to F344 rats for 7 days, and the biodistribution of fluorescent NPs was analyzed in different organs. Results The highest amount of particles (% total dose/g) was detected for both treatments in the spleen, followed by intestine and kidney, and then by liver, lung, heart and brain, with no significant difference between PLGA and PLGA/Chi NPs. Conclusion Only a small percentage of orally delivered NPs was detected in the analyzed organs. The positive charge conferred by chitosan was not sufficient to improve the absorption of the PLGA/Chi NPs over that of PLGA NPs. PMID:25491670

  1. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

    PubMed

    Sanchez-Gaytan, Brenda L; Fay, Francois; Lobatto, Mark E; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E M; van Rijs, Sarian M; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J; Langer, Robert; Fayad, Zahi A; Mulder, Willem J M

    2015-03-18

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA-HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA-HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers.

  2. PLGA Nanoparticles as Subconjunctival Injection for Management of Glaucoma.

    PubMed

    Salama, Hamed A; Ghorab, Mahmoud; Mahmoud, Azza A; Abdel Hady, Mayssa

    2017-02-21

    Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), could be a promising system for targeting ocular drug delivery. The objective of this work was to investigate the possibility of encapsulating brinzolamide in PLGA nanoparticles in order to be applied as a subconjunctival injection that could represent a starting point for developing new therapeutic strategies against increase in ocular pressure. The brinzolamide-loaded PLGA nanoparticles were fabricated using emulsion-diffusion-evaporation method with varying concentrations of Tween 80 or poloxamer 188 (Plx) in aqueous and organic phases. The nanoparticles were characterized in terms of particle size and size distribution, entrapment efficiency and in-vitro drug release pattern as well as DSC and X-ray analysis. Nanoparticles prepared using Tween 80 in the aqueous phase showed higher encapsulation efficiency and smaller particle size-values compared to those prepared using Plx. Furthermore, the addition of Plx 188 or Brij 97 to the organic phase in the formulation containing Tween 80 in the aqueous phase led to an increase in the particle diameter-values of the obtained nanoparticles. The nanoparticles had the capacity to release the brinzolamide in a biphasic release profile. The nanoparticles were spherical in shape and the drug was entraped in the nanoparticles in an amorphous form. Selected nanoparticles, injected subconjunctivally in normotensive Albino rabbits, were able to reduce the IOP for up to 10 days. Nanoparticles loaded with brinzolamide with lower particle size were able to reduce the IOP for longer period compared to those with higher particle size. Histopathological studies for the anterior cross sections of the rabbits' eyes revealed that the tested nanoparticles were compatible with the ocular tissue. The overall results support that PLGA nanoparticles, applied as subconjunctival injection, can be considered as a promising carrier for

  3. [Transport of PLGA nanoparticles across Caco-2/HT29-MTX co-cultured cells].

    PubMed

    Wen, Zhen; Li, Gang; Lin, Dong-Hai; Wang, Jun-Teng; Qin, Li-Fang; Guo, Gui-Ping

    2013-12-01

    The present study is to establish Caco-2/HT29-MTX co-cultured cells and investigate the transport capability of PLGA nanoparticles with different surface chemical properties across Caco-2/HT29-MTX co-cultured cells. PLGA-NPs, mPEG-PLGA-NPs and chitosan coated PLGA-NPs were prepared by nanoprecipitation method using poly(lactic-co-glycolic acid) as carrier material with surface modified by methoxy poly(ethylene glycol) and chitosan. The particle size and zeta potential of nanoparticles were measured by dynamic light scattering. Coumarin 6 was used as a fluorescent marker in the transport of nanoparticles investigated by confocal laser scanning microscopy. The transport of furanodiene (FDE) loaded nanoparticles was quantitively determined by high performance liquid chromatography. Colchicine and nocodazole were used in the transport study to explore the involved endocytosis mechanisms of nanoparticles. Distribution of the tight junction proteins ZO-1 was also analyzed by immunofluorescence staining. The results showed that the nanoparticles dispersed uniformly. The zeta potential of PLGA-NPs was negative, the mPEG-PLGA-NPs was close to neutral and the CS-PLGA-NPs was positive. The entrapment efficiency of FDE in all nanoparticles was higher than 75%. The transport capability of mPEG-PLGA-NPs across Caco-2/HT29-MTX co-cultured cells was higher than that of PLGA-NPs and CS-PLGA-NPs. Colchicine and nocodazole could significantly decrease the transport amount of nanoparticles. mPEG-PLGA-NPs could obviously reduce the distribution of ZO-1 protein than PLGA-NPs and CS-PLGA-NPs. The transport mechanism of PLGA-NPs and mPEG-PLGA-NPs were indicated to be a combination of endocytosis and paracellular way, while CS-PLGA-NPs mainly relied on the endocytosis way. PEG coating could shield the surface charge and enhance the hydrophilicity of PLGA nanoparticles, which leads mPEG-PLGA-NPs to possess higher anti-adhesion activity. As a result, mPEG-PLGA-NPs could penetrate the mucus

  4. Systemic delivery to central nervous system by engineered PLGA nanoparticles

    PubMed Central

    Cai, Qiang; Wang, Long; Deng, Gang; Liu, Junhui; Chen, Qianxue; Chen, Zhibiao

    2016-01-01

    Neurological disorders are an important global public health problem, but pharmaceutical treatments are limited due to drug access to the central nervous system being restricted by the blood-brain barrier (BBB). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are one of the most promising drug and gene delivery systems for crossing the BBB. While these systems offer great promise, PLGA NPs also have some intrinsic drawbacks and require further engineering for clinical and research applications. Multiple strategies have been developed for using PLGA NPs to deliver compounds across the BBB. We classify these strategies into three categories according to the adaptations made to the PLGA NPs (1) to facilitate travel from the injection site (pre-transcytosis strategies); (2) to enhance passage across the brain endothelial cells (BBB transcytosis strategies) and (3) to achieve targeting of the impaired nervous system cells (post-transcytosis strategies). PLGA NPs modified according to these three strategies are denoted first, second, and third generation NPs, respectively. We believe that fusing these three strategies to engineer multifunctional PLGA NPs is the only way to achieve translational applications. PMID:27158367

  5. Interaction of PLGA and trimethyl chitosan modified PLGA nanoparticles with mixed anionic/zwitterionic phospholipid bilayers studied using molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Novak, Brian; Astete, Carlos; Sabliov, Cristina; Moldovan, Dorel

    2012-02-01

    Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer. Nanoparticles of PLGA are commonly used for drug delivery applications. The interaction of the nanoparticles with the cell membrane may influence the rate of their uptake by cells. Both PLGA and cell membranes are negatively charged, so adding positively charged polymers such as trimethyl chitosan (TMC) which adheres to the PLGA particles improves their cellular uptake. The interaction of 3 nm PLGA and TMC-modified-PLGA nanoparticles with lipid bilayers composed of mixtures of phosphatidylcholine and phosphatidylserine lipids was studied using molecular dynamics simulations. The free energy profiles as function of nanoparticles position along the normal direction to the bilayers were calculated, the distribution of phosphatidylserine lipids as a function of distance of the particle from the bilayer was calculated, and the time scale for particle motion in the directions parallel to the bilayer surface was estimated.

  6. Engineering of lipid-coated PLGA nanoparticles with a tunable payload of diagnostically active nanocrystals for medical imaging†

    PubMed Central

    Mieszawska, Aneta J.; Gianella, Anita; Cormode, David P.; Zhao, Yiming; Meijerink, Andries; Langer, Robert; Farokhzad, Omid C.; Fayad, Zahi A.; Mulder, Willem J. M.

    2013-01-01

    Polylactic-co-glycolic acid (PLGA) based nanoparticles are biocompatible and biodegradable and therefore have been extensively investigated as therapeutic carriers. Here, we engineered diagnostically active PLGA nanoparticles that incorporate high payloads of nanocrystals into their core for tunable bioimaging features. We accomplished this through esterification reactions of PLGA to generate polymers modified with nanocrystals. The PLGA nanoparticles formed from modified PLGA polymers that were functionalized with either gold nanocrystals or quantum dots exhibited favorable features for computed tomography and optical imaging, respectively. PMID:22555311

  7. Surface modification of PLGA nanoparticles by carbopol to enhance mucoadhesion and cell internalization.

    PubMed

    Surassmo, Suvimol; Saengkrit, Nattika; Ruktanonchai, Uracha Rungsardthong; Suktham, Kunat; Woramongkolchai, Noppawan; Wutikhun, Tuksadon; Puttipipatkhachorn, Satit

    2015-06-01

    Mucoadhesive poly (lactic-co-glycolic acid) (PLGA) nanoparticles having a modified shell-matrix derived from polyvinyl alcohol (PVA) and Carbopol (CP), a biodegradable polymer coating, to improve the adhesion and cell transfection properties were developed. The optimum formulations utilized a CP concentration in the range of 0.05-0.2%w/v, and were formed using modified emulsion-solvent evaporation technique. The resulting CP-PLGA nanoparticles were characterized in terms of their physical and chemical properties. The absorbed CP on the PLGA shell-matrix was found to affect the particle size and surface charge, with 0.05% CP giving rise to smooth spherical particles (0.05CP-PLGA) with the smallest size (285.90 nm), and strong negative surface charge (-25.70 mV). The introduction of CP results in an enhancement of the mucoadhesion between CP-PLGA nanoparticles and mucin particles. In vitro cell internalization studies highlighted the potential of 0.05CP-PLGA nanoparticles for transfection into SiHa cells, with uptake being time dependent. Additionally, cytotoxicity studies of CP-PLGA nanoparticles against SiHa cancer cells indicated that low concentrations of the nanoparticles were non-toxic to cells (cell viability >80%). From the various formulations studied, 0.05CP-PLGA nanoparticles proved to be the optimum model carrier having the required mucoadhesive profile and could be an alternative therapeutic efficacy carrier for targeted mucosal drug delivery systems with biodegradable polymer.

  8. Hemocompatibility of folic-acid-conjugated amphiphilic PEG-PLGA copolymer nanoparticles for co-delivery of cisplatin and paclitaxel: treatment effects for non-small-cell lung cancer.

    PubMed

    He, Zelai; Shi, Zengfang; Sun, Wenjie; Ma, Jing; Xia, Junyong; Zhang, Xiangyu; Chen, Wenjun; Huang, Jingwen

    2016-06-01

    In this study, we used folic-acid-modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) to encapsulate cisplatin and paclitaxel (separately or together), and evaluated their antitumor effects against lung cancer; this study was conducted in order to investigate the antitumor effects of the co-delivery of cisplatin and paclitaxel by a targeted drug delivery system. Blood compatibility assays and complement activation tests revealed that FA-PEG-PLGA nanoparticles did not induce blood hemolysis, blood clotting, or complement activation. The results also indicated that FA-PEG-PLGA nanoparticles had no biotoxic effects, the drug delivery system allowed controlled release of the cargo molecules, and the co-delivery of cisplatin and paclitaxel efficiently induces cancer cell apoptosis and cell cycle retardation. In addition, co-delivery of cisplatin and paclitaxel showed the ability to suppress xenograft lung cancer growth and prolong the survival time of xenografted mice. These results implied that FA-PEG-PLGA nanoparticles can function as effective carriers of cisplatin and paclitaxel, and that co-delivery of cisplatin and paclitaxel by FA-PEG-PLGA nanoparticles results in more effective antitumor effects than the combination of free-drugs or single-drug-loaded nanoparticles.

  9. HDL-Mimetic PLGA Nanoparticle To Target Atherosclerosis Plaque Macrophages

    PubMed Central

    Sanchez-Gaytan, Brenda L.; Fay, Francois; Lobatto, Mark E.; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E. M.; van Rijs, Sarian M.; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J.; Langer, Robert; Fayad, Zahi A.; Mulder, Willem J M

    2015-01-01

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA–HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA–HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers. PMID:25650634

  10. Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

    PubMed Central

    2013-01-01

    Background Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues. Methods PLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells. Results Size, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, −11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, −5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg). Conclusion In conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may

  11. [Transport of mPEG-PLGA nanoparticles across the rat nasal mucosa].

    PubMed

    Wang, Jun-Teng; Lin, Dong-Hai; Qin, Li-Fang; Wen, Zhen; Guo, Gui-Ping

    2013-05-01

    To investigate the effects of particle size, mPEG molecular weight, coating density and zeta potential of monomethoxyl poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles on their transportation across the rat nasal mucosa, mPEG-PLGA-NPs with different mPEG molecular weights (M(r) 1 000, 2 000) and coating density (0, 5%, 10%, 15%) and chitosan coated PLGA-NP, which loaded coumarin-6 as fluorescent marker, were prepared with the nanoprecipitation method and emulsion-solvent evaporation method, and determine their particle size, zeta potential, the efficiency of fluorescent labeling, in vitro leakage rate and the stability with the lysozyme were determined. The effects of physical and chemical properties on the transmucosal transport of the fluorescent nanoparticles were investigated by confocal laser scanning microscopy (CLSM). The result showed that the size of nanoparticles prepared with nanoprecipitation method varied between 120 and 200 nm; the size of nanoparticles prepared with emulsion-solvent evaporation method varied between 420 and 450 nm. Nanoparticles dispersed uniformly; the zeta potential of PLGA-NPs was negative; mPEG-PLGA-NPs was close to neutral; chitosan coated PLGA-NPs was positive; and the efficiency of fluorescent labeling were higher than 80%. In vitro leak was less than 5% within 4 h and nanoparticles were basically stable with lysozyme. The CLSM results show that the transportation efficiency of mPEG-PLGA-NPs with a high PEG coating density and high mPEG molecular weight was significantly higher than that of uncoated PLGA nanoparticles and also that of chitosan coated PLGA-NPs (P < 0.05). The hydrophilcity, zeta potential and particle size of nanoparticles play important roles on the efficiency of mPEG-PLGA nanoparticles to transport across the rat nasal mucosa.

  12. Radiolabeling of Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles with Biotinylated F-18 Prosthetic Groups and Imaging of Their Delivery to the Brain with Positron Emission Tomography

    PubMed Central

    2015-01-01

    The avidin–biotin interaction permits rapid and nearly irreversible noncovalent linkage between biotinylated molecules and avidin-modified substrates. We designed a biotinylated radioligand intended for use in the detection of avidin-modified polymer nanoparticles in tissue with positron emission tomography (PET). Using an F-18 labeled prosthetic group, [18F]4-fluorobenzylamine, and a commercially available biotin derivate, NHS-PEG4-biotin, [18F]-fluorobenzylamide-poly(ethylene glycol)4-biotin ([18F]NPB4) was prepared with high purity and specific activity. The attachment of the [18F]NPB4 radioligand to avidin-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles was tested by using PET imaging to measure the kinetics of convection-enhanced delivery (CED) of nanoparticles of varying size to the rat brain. PET imaging enabled the direct observation of nanoparticle delivery by measurement of the spatial volume of distribution of radiolabeled nanoparticles as a function of time, both during and after the infusion. This work thus validates new methods for radiolabeling PEG-biotin derivatives and also provides insight into the fate of nanoparticles that have been infused directly into the brain. PMID:25322194

  13. Co-delivery of cisplatin and paclitaxel by folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles for the treatment of non-small lung cancer

    PubMed Central

    He, Zelai; Huang, Jingwen; Xu, Yuanyuan; Zhang, Xiangyu; Teng, Yanwei; Huang, Can; Wu, Yufeng; Zhang, Xi; Zhang, Huijun; Sun, Wenjie

    2015-01-01

    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

  14. Galactose decorated PLGA nanoparticles for hepatic delivery of acyclovir.

    PubMed

    Gupta, Swati; Agarwal, Abhinav; Gupta, Nishant Kumar; Saraogi, Gauravkant; Agrawal, Himanshu; Agrawal, G P

    2013-12-01

    The present study explores prospective of surface tailored nanoparticles for targeted delivery of acyclovir along with the interception of minimal side effects. Acyclovir loaded plain and galactosylated poly lectic co glycolic acid (PLGA) nanoparticles were efficiently prepared and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), size, polydispersity index, zeta potential, and entrapment efficiency. The formulations were evaluated for in vitro drug release and hemolysis. Further, biodistribution study and fluorescent microscopic studies were carried out to determine the targeting potential of formulations. SEM revealed smooth morphology and spherical shape of the nanoparticles. In vitro, the galactosylated nanoparticles were found to be least hemolytic and exhibited a sustained release pattern. In vivo studies exhibited an augmented bioavailability, increased residence time and enhanced delivery of acyclovir to the liver upon galactosylation. It may therefore be concluded that galactose conjugated PLGA nanoparticles can be used suitably as vehicles for delivery of bioactives specifically to the hepatic tissues and may be thus exploited in the effective management of various liver disorders.

  15. Bone Regeneration from PLGA Micro-Nanoparticles

    PubMed Central

    Ortega-Oller, Inmaculada; Padial-Molina, Miguel; Galindo-Moreno, Pablo; O'Valle, Francisco; Jódar-Reyes, Ana Belén; Peula-García, Jose Manuel

    2015-01-01

    Poly-lactic-co-glycolic acid (PLGA) is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2). Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed. PMID:26509156

  16. Hyaluronic acid-decorated dual responsive nanoparticles of Pluronic F127, PLGA, and chitosan for targeted co-delivery of doxorubicin and irinotecan to eliminate cancer stem-like cells

    PubMed Central

    Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Xu, Ronald X.; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

    2016-01-01

    Dual responsive nanoparticles are developed for co-delivery of multiple anticancer drugs to target the drug resistance mechanisms of cancer stem-like cells (CSCs). The nanoparticles consist of four polymers approved by the Food and Drug Administration (FDA) for medical use: Poly(D,L-lactide-co-glycolide) (PLGA), Pluronic F127 (PF127), chitosan, and hyaluronic acid (HA). By combining PLGA and PF127 together, more stable and uniform-sized nanoparticles can be obtained than using PLGA or PF127 alone. The HA is used for not only actively targeting CSCs to reduce their drug resistance due to dormancy (i.e., slow metabolism), but also replacing the commonly used poly(vinyl alcohol) as a stabilizing agent to synthesize the nanoparticles using the double-emulsion approach and to allow for acidic pH-triggered drug release and thermal responsiveness. Besides minimizing drug efflux from CSCs, the nanoparticles encapsulated with doxorubicin hydrochloride (DOX, hydrophilic) and irinotecan (CPT, hydrophobic) to inhibit the activity of topoisomerases II and I, respectively, can fight against the CSC drug resistance associated with their enhanced DNA repair and anti-apoptosis. Ultimately, the two drugs-laden nanoparticles can be used to efficiently destroy the CSCs both in vitro and in vivo with up to ~500 times of enhancement compared to the simple mixture of the two drugs. PMID:26344365

  17. Efficient production of retroviruses using PLGA/bPEI-DNA nanoparticles and application for reprogramming somatic cells.

    PubMed

    Seo, Eun Jin; Jang, Il Ho; Do, Eun Kyoung; Cheon, Hyo Cheon; Heo, Soon Chul; Kwon, Yang Woo; Jeong, Geun Ok; Kim, Ba Reun; Kim, Jae Ho

    2013-01-01

    Reprogramming of somatic cells to pluripotent cells requires the introduction of factors driving fate switches. Viral delivery has been the most efficient method for generation of induced pluripotent stem cells. Transfection, which precedes virus production, is a commonly-used process for delivery of nucleic acids into cells. The aim of this study is to evaluate the efficiency of PLGA/ bPEI nanoparticles in transfection and virus production. Using a modified method of producing PLGA nanoparticles, PLGA/bPEI-DNA nanoparticles were examined for transfection efficiency and virus production yield in comparison with PLGA-DNA, bPEI-DNA nanoparticles or liposome-DNA complexes. After testing various ratios of PLGA, bPEI, and DNA, the ratio of 6:3:1 (PLGA:bPEI:DNA, w/w/w) was determined to be optimal, with acceptable cellular toxicity. PLGA/bPEI-DNA (6:3:1) nanoparticles showed superior transfection efficiency, especially in multiple gene transfection, and viral yield when compared with liposome-DNA complexes. The culture supernatants of HEK293FT cells transfected with PLGA/bPEI-DNA of viral constructs containing reprogramming factors (Oct4, Sox2, Klf4, or c-Myc) successfully and more efficiently generated induced pluripotent stem cell colonies from mouse embryonic fibroblasts. These results strongly suggest that PLGA/bPEI-DNA nanoparticles can provide significant advantages in studying the effect of multiple factor delivery such as in reprogramming or direct conversion of cell fate.

  18. PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing.

    PubMed

    Chereddy, Kiran Kumar; Her, Charles-Henry; Comune, Michela; Moia, Claudia; Lopes, Alessandra; Porporato, Paolo E; Vanacker, Julie; Lam, Martin C; Steinstraesser, Lars; Sonveaux, Pierre; Zhu, Huijun; Ferreira, Lino S; Vandermeulen, Gaëlle; Préat, Véronique

    2014-11-28

    Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles.

  19. pH-Responsive PLGA Nanoparticle for Controlled Payload Delivery of Diclofenac Sodium

    PubMed Central

    Khanal, Shalil; Adhikari, Udhab; Rijal, Nava P.; Bhattarai, Shanta R.; Sankar, Jagannathan; Bhattarai, Narayan

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) based nanoparticles have gained increasing attention in delivery applications due to their capability for controlled drug release characteristics, biocompatibility, and tunable mechanical, as well as degradation, properties. However, thorough study is always required while evaluating potential toxicity of the particles from dose dumping, inconsistent release and drug-polymer interactions. In this research, we developed PLGA nanoparticles modified by chitosan (CS), a cationic and pH responsive polysaccharide that bears repetitive amine groups in its backbone. We used a model drug, diclofenac sodium (DS), a nonsteroidal anti-inflammatory drug (NSAID), to study the drug loading and release characteristics. PLGA nanoparticles were synthesized by double-emulsion solvent evaporation technique. The nanoparticles were evaluated based on their particle size, surface charge, entrapment efficacy, and effect of pH in drug release profile. About 390–420 nm of average diameters and uniform morphology of the particles were confirmed by scanning electron microscope (SEM) imaging and dynamic light scattering (DLS) measurement. Chitosan coating over PLGA surface was confirmed by FTIR and DLS. Drug entrapment efficacy was up to 52%. Chitosan coated PLGA showed a pH responsive drug release in in vitro. The release was about 45% more at pH 5.5 than at pH 7.4. The results of our study indicated the development of chitosan coating over PLGA nanoparticle for pH dependent controlled release DS drug for therapeutic applications. PMID:27490577

  20. Preparation, characterization, and anticancer efficacy of evodiamine-loaded PLGA nanoparticles.

    PubMed

    Zou, Lidi; Chen, Fengqian; Bao, Jiaolin; Wang, Shengpeng; Wang, Lu; Chen, Meiwan; He, Chengwei; Wang, Yitao

    2016-01-01

    Evodiamine (EVO) is a plant-derived indolequinazoline alkaloid with potential anticancer activity. However, low bioavailability caused by its poor water solubility limits it anticancer efficacy in clinic. To enhance the solubility and improve the bioavailability of EVO, a delivery system based on poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with EVO (EVO-PLGA NPs) for treating breast cancer was prepared in this study. The physicochemical characterization and in vitro antitumor evaluation of EVO-PLGA NPs were determined. EVO-PLGA NPs could persistently control the release of EVO for 180 h. 3-[4,5-Dimethyl-2-thiazolyl]-2,5-diphenyl tetrazolium bromide (MTT) assessment and colony formation assay showed that EVO-PLGA NPs could enhance the toxicity and the proliferation inhibition effect of EVO on MCF-7 breast cancer cells. EVO-PLGA NPs did not strengthen G2/M arrest effect of EVO-treated cells after 24h incubation. Meanwhile, EVO-PLGA NPs could increase the expression of cyclin B1 and decrease the expression of β-actin. Taken together, these results suggested that -PLGA NPs is promising for improving anticancer efficacy of EVO in breast cancer therapy.

  1. Anticancer Activity of Nanoparticles Based on PLGA and its Co-polymer: In-vitro Evaluation

    PubMed Central

    Amjadi, Issa; Rabiee, Mohammad; Hosseini, Motahare-Sadat

    2013-01-01

    Attempts have been made to prepare nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) and doxorubicin. Biological evaluation and physio-chemical characterizations were performed to elucidate the effects of initial drug loading and polymer composition on nanoparticle properties and its antitumor activity. PLGA nanoparticles were formulated by sonication method. Lactide/glycolide ratio and doxorubicin amounts have been tailored. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were employed to identify the presence of doxorubicin within nanospheres. The in vitro release studies were performed to determine the initial ant net release rates over 24 h and 20 days, respectively. Furthermore, cytotoxicity assay was measured to evaluate therapeutic potency of doxorubicin-loaded nanoparticles. Spectroscopy and thermal results showed that doxorubicin was loaded into the particles successfully. It was observed that lactide/glycolide content of PLGA nanoparticles containing doxorubicin has more prominent role in tuning particle characteristics. Doxorubicin release profiles from PLGA 75 nanospheres demonstrated that the cumulative release rate increased slightly and higher initial burst was detected in comparison to PLGA 50 nanoparticles. MTT data revealed doxorubicin induced antitumor activity was enhanced by encapsulation process, and increasing drug loading and glycolide portion. The results led to the conclusion that by controlling the drug loading and the polymer hydrophilicity, we can adjust the drug targeting and blood clearance, which may play a more prominent role for application in chemotherapy. PMID:24523742

  2. An HPLC method for microanalysis and pharmacokinetics of marine sulfated polysaccharide PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles in rat plasma.

    PubMed

    Li, Peng-Li; Li, Chun-Xia; Xue, Yi-Ting; Li, Hai-Hua; Liu, Hong-Bing; He, Xiao-Xi; Yu, Guang-Li; Guan, Hua-Shi

    2013-04-02

    This study was aimed at developing a sensitive and selective HPLC method with postcolumn fluorescence derivatization for the detection of propylene glycol alginate sodium sulfate (PSS) in rat plasma. Plasma samples were prepared by a simple and fast ultrafiltration method. PSS was extracted from rat plasma with D-glucuronic acid as internal standard. Isocratic chromatographic separation was performed on a TSKgel G2500 PWxL column with the mobile phase of 0.1 M sodium sulfate at a flow rate of 0.5 mL/min. Analyte detection was achieved by fluorescence detection (FLD) at 250 nm (excitation) and 435 nm (emission) using guanidine hydrochloride as postcolumn derivatizing reagent in an alkaline medium at 120 °C. The calibration curve was linear over a concentration range of 1-500 μg/mL, and the lower limit of detection (LLOD) was found to be 250 ng/mL. This validated method was applied successfully to the pharmacokinetic study of PSS and PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (PSS-NP) in rat plasma after a single intravenous (PSS only) and oral administration (PSS and PSS-NP). Significant differences in the main pharmacokinetic parameters of PSS and PSS-NP were observed. The relative bioavailability of PSS-NP was 190.10% compared with PSS which shows that PSS-NP can improve oral bioavailability.

  3. An HPLC Method for Microanalysis and Pharmacokinetics of Marine Sulfated Polysaccharide PSS-Loaded Poly Lactic-co-Glycolic Acid (PLGA) Nanoparticles in Rat Plasma

    PubMed Central

    Li, Peng-Li; Li, Chun-Xia; Xue, Yi-Ting; Li, Hai-Hua; Liu, Hong-Bing; He, Xiao-Xi; Yu, Guang-Li; Guan, Hua-Shi

    2013-01-01

    This study was aimed at developing a sensitive and selective HPLC method with postcolumn fluorescence derivatization for the detection of propylene glycol alginate sodium sulfate (PSS) in rat plasma. Plasma samples were prepared by a simple and fast ultrafiltration method. PSS was extracted from rat plasma with d-glucuronic acid as internal standard. Isocratic chromatographic separation was performed on a TSKgel G2500 PWxL column with the mobile phase of 0.1 M sodium sulfate at a flow rate of 0.5 mL/min. Analyte detection was achieved by fluorescence detection (FLD) at 250 nm (excitation) and 435 nm (emission) using guanidine hydrochloride as postcolumn derivatizing reagent in an alkaline medium at 120 °C. The calibration curve was linear over a concentration range of 1–500 μg/mL, and the lower limit of detection (LLOD) was found to be 250 ng/mL. This validated method was applied successfully to the pharmacokinetic study of PSS and PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (PSS-NP) in rat plasma after a single intravenous (PSS only) and oral administration (PSS and PSS-NP). Significant differences in the main pharmacokinetic parameters of PSS and PSS-NP were observed. The relative bioavailability of PSS-NP was 190.10% compared with PSS which shows that PSS-NP can improve oral bioavailability. PMID:23549283

  4. Effects of Microemulsion Preparation Conditions on Drug Encapsulation Efficiency of PLGA Nanoparticles

    NASA Astrophysics Data System (ADS)

    Ng, Set Hui; Ooi, Ing Hong

    2011-12-01

    Emulsion solvent evaporation technique is widely used to prepare nanoparticles of many organic polymer drug carriers. The mechanism of nanoparticle generation by this technique involves oil-in-water (O/W) microemulsion formation followed by solvent evaporation. Various microemulsion preparation conditions can affect the encapsulation efficiency of drug in the nanoparticulate carrier. In this study, emulsifying speed, emulsifying temperature, and organic-to-aqueous phase ratio were varied and the resulting encapsulation efficiency of a model drug in Poly(Lactide-co-Glycolide) (PLGA) nanoparticles was determined. The organic phase containing PLGA and a model drug dissolved in chloroform was first dispersed in an aqueous solution containing 0.5 %(w/v) Poly(vinyl alcohol) (PVA), which was then homogenized at high speeds. The resulting O/W microemulsion was subsequently subjected to stirring at room temperature for four hours during which the solvent diffused and evaporated gradually. The fine white suspension was centrifuged and freeze-dried. The model drug loading in the PLGA nanoparticles was determined using UV spectrophotometry. Results showed that the encapsulation efficiency of a model drug, salicylic acid, ranged from 8.5% to 17% depending on the microemulsion preparation conditions. Under the same temperature (15 °C) and homogenization speed (19000 rpm) conditions studied, a relatively high organic-to-aqueous phase ratio (1:5) provided salicylic acid loaded PLGA nanoparticles with significantly higher drug encapsulation efficiency. In addition, under all microemulsion preparation conditions, PLGA nanoparticles obtained after solvent evaporation and freeze drying were spherical and aggregation between the nanoparticles was not observed under a high power microscope. This indicates that PLGA nanoparticles with desirable amount of drug and with anticipated size and shape can be realized by controlling emulsification process conditions.

  5. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile

    PubMed Central

    Rafiei, Pedram; Haddadi, Azita

    2017-01-01

    Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug’s pharmacokinetics related to the conventional formulation. Poly(lactide-co-glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs’ long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA–PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel’s pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs. PMID:28184163

  6. Transferrin surface-modified PLGA nanoparticles-mediated delivery of a proteasome inhibitor to human pancreatic cancer cells.

    PubMed

    Frasco, Manuela F; Almeida, Gabriela M; Santos-Silva, Filipe; Pereira, Maria do Carmo; Coelho, Manuel A N

    2015-04-01

    The aim of this study was to develop a drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles for an efficient and targeted action of the proteasome inhibitor bortezomib against pancreatic cancer cells. The PLGA nanoparticles were formulated with a poloxamer, and further surface-modified with transferrin for tumor targeting. The nanoparticles were characterized as polymer carriers of bortezomib, and the cellular uptake and growth inhibitory effects were evaluated in pancreatic cells. Cellular internalization of nanoparticles was observed in normal and cancer cells, but with higher uptake by cancer cells. The sustained release of the loaded bortezomib from PLGA nanoparticles showed cytotoxic effects against pancreatic normal and cancer cells. Noteworthy differential cytotoxicity was attained by transferrin surface-modified PLGA nanoparticles since significant cell growth inhibition by delivered bortezomib was only observed in cancer cells. These findings demonstrate that the ligand transferrin enhanced the targeted delivery of bortezomib-loaded PLGA nanoparticles to pancreatic cancer cells. These in vitro results highlight the transferrin surface-modified PLGA nanoparticles as a promising system for targeted delivery of anticancer drugs.

  7. Oral Delivery of DMAB-Modified Docetaxel-Loaded PLGA-TPGS Nanoparticles for Cancer Chemotherapy

    NASA Astrophysics Data System (ADS)

    Chen, Hongbo; Zheng, Yi; Tian, Ge; Tian, Yan; Zeng, Xiaowei; Liu, Gan; Liu, Kexin; Li, Lei; Li, Zhen; Mei, Lin; Huang, Laiqiang

    2011-12-01

    Three types of nanoparticle formulation from biodegradable PLGA-TPGS random copolymer were developed in this research for oral administration of anticancer drugs, which include DMAB-modified PLGA nanoparticles, unmodified PLGA-TPGS nanoparticles and DMAB-modified PLGA-TPGS nanoparticles. Firstly, the PLGA-TPGS random copolymer was synthesized and characterized. DMAB was used to increase retention time at the cell surface, thus increasing the chances of particle uptake and improving oral drug bioavailability. Nanoparticles were found to be of spherical shape with an average particle diameter of around 250 nm. The surface charge of PLGA-TPGS nanoparticles was changed to positive after DMAB modification. The results also showed that the DMAB-modified PLGA-TPGS nanoparticles have significantly higher level of the cellular uptake than that of DMAB-modified PLGA nanoparticles and unmodified PLGA-TPGS nanoparticles. In vitro, cytotoxicity experiment showed advantages of the DMAB-modified PLGA-TPGS nanoparticle formulation over commercial Taxotere® in terms of cytotoxicity against MCF-7 cells. In conclusion, oral chemotherapy by DMAB-modified PLGA-TPGS nanoparticle formulation is an attractive and promising treatment option for patients.

  8. Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis.

    PubMed

    Arias, José L; Unciti-Broceta, Juan D; Maceira, José; Del Castillo, Teresa; Hernández-Quero, José; Magez, Stefan; Soriano, Miguel; García-Salcedo, José A

    2015-01-10

    Targeted delivery of therapeutics is an alternative approach for the selective treatment of infectious diseases. The surface of African trypanosomes, the causative agents of African trypanosomiasis, is covered by a surface coat consisting of a single variant surface glycoprotein, termed VSG. This coat is recycled by endocytosis at a very high speed, making the trypanosome surface an excellent target for the delivery of trypanocidal drugs. Here, we report the design of a drug nanocarrier based on poly ethylen glycol (PEG) covalently attached (PEGylated) to poly(D,L-lactide-co-glycolide acid) (PLGA) to generate PEGylated PLGA nanoparticles. This nanocarrier was coupled to a single domain heavy chain antibody fragment (nanobody) that specifically recognizes the surface of the protozoan pathogen Trypanosoma brucei. Nanoparticles were loaded with pentamidine, the first-line drug for T. b. gambiense acute infection. An in vitro effectiveness assay showed a 7-fold decrease in the half-inhibitory concentration (IC50) of the formulation relative to free drug. Furthermore, in vivo therapy using a murine model of African trypanosomiasis demonstrated that the formulation cured all infected mice at a 10-fold lower dose than the minimal full curative dose of free pentamidine and 60% of mice at a 100-fold lower dose. This nanocarrier has been designed with components approved for use in humans and loaded with a drug that is currently in use to treat the disease. Moreover, this flexible nanobody-based system can be adapted to load any compound, opening a range of new potential therapies with application to other diseases.

  9. Drug release behavior of poly (lactic-glycolic acid) grafting from sodium alginate (ALG-g-PLGA) prepared by direct polycondensation.

    PubMed

    Shi, Gang; Ding, Yuanyuan; Zhang, Xin; Wu, Luyan; He, Fei; Ni, Caihua

    2015-01-01

    Hydrophobically modified sodium alginate, poly (lactic-glycolic acid) grafting from sodium alginate (ALG-g-PLGA), was successfully synthesized through direct one-step polymerization of sodium alginate, glycolic acid, and lactic acid. ALG-g-PLGA self-assembled to colloidal nanoparticles and subsequently hydrogel microspheres were obtained by crosslinking ALG-g-PLGA nanoparticles in the solution of calcium chloride. The modified hydrogel microspheres could be used as the drug delivery vehicles for a hydrophobic ibuprofen. Compared with sodium alginate, ALG-g-PLGA demonstrated an improved drug loading rate, encapsulation efficiency, and prolonged release speed. The products, as novel and highly promising biomaterials, have potential applications.

  10. Biodegradable PLGA- b-PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system

    NASA Astrophysics Data System (ADS)

    Locatelli, Erica; Comes Franchini, Mauro

    2012-12-01

    During the past decades many synthetic polymers have been studied for nanomedicine applications and in particular as drug delivery systems. For this purpose, polymers must be non-toxic, biodegradable, and biocompatible. Polylactic- co-glycolic acid (PLGA) is one of the most studied polymers due to its complete biodegradability and ability to self-assemble into nanometric micelles that are able to entrap small molecules like drugs and to release them into body in a time-dependent manner. Despite fine qualities, using PLGA polymeric nanoparticles for in vivo applications still remains an open challenge due to many factors such as poor stability in water, big diameter (150-200 nm), and the removal of these nanocarriers from the blood stream by the liver and spleen thus reducing the concentration of drugs drastically in tumor tissue. Polyethylene glycol (PEG) is the most used polymers for drug delivery applications and the first PEGylated product is already on the market for over 20 years. This is due to its stealth behavior that inhibits the fast recognition by the immune system (opsonization) and generally leads to a reduced blood clearance of nanocarriers increasing blood circulation time. Furthermore, PEG is hydrophilic and able to stabilize nanoparticles by steric and not ionic effects especially in water. PLGA-PEG block copolymer is an emergent system because it can be easily synthesized and it possesses all good qualities of PLGA and also PEG capability so in the last decade it arose as one of the most promising systems for nanoparticles formation, drug loading, and in vivo drug delivery applications. This review will discuss briefly on PLGA- b-PEG synthesis and physicochemical properties, together with its improved qualities with respect to the single PLGA and PEG polymers. Moreover, we will focus on but in particular will treat nanoparticles formation and uses as new drug delivery system for nanomedical applications.

  11. Interactions of PLGA nanoparticles with blood components: protein adsorption, coagulation, activation of the complement system and hemolysis studies.

    PubMed

    Fornaguera, Cristina; Calderó, Gabriela; Mitjans, Montserrat; Vinardell, Maria Pilar; Solans, Conxita; Vauthier, Christine

    2015-04-14

    The intravenous administration of poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been widely reported as a promising alternative for delivery of drugs to specific cells. However, studies on their interaction with diverse blood components using different techniques are still lacking. Therefore, in the present work, the interaction of PLGA nanoparticles with blood components was described using different complementary techniques. The influence of different encapsulated compounds/functionalizing agents on these interactions was also reported. It is worth noting that all these techniques can be simply performed, without the need for highly sophisticated apparatus or skills. Moreover, their transference to industries and application of quality control could be easily performed. Serum albumin was adsorbed onto all types of tested nanoparticles. The saturation concentration was dependent on the nanoparticle size. In contrast, fibrinogen aggregation was dependent on nanoparticle surface charge. The complement activation was also influenced by the nanoparticle functionalization; the presence of a functionalizing agent increased complement activation, while the addition of an encapsulated compound only caused a slight increase. None of the nanoparticles influenced the coagulation cascade at low concentrations. However, at high concentrations, cationized nanoparticles did activate the coagulation cascade. Interactions of nanoparticles with erythrocytes did not reveal any hemolysis. Interactions of PLGA nanoparticles with blood proteins depended both on the nanoparticle properties and the protein studied. Independent of their loading/surface functionalization, PLGA nanoparticles did not influence the coagulation cascade and did not induce hemolysis of erythrocytes; they could be defined as safe concerning induction of embolization and cell lysis.

  12. In vivo uptake and acute immune response to orally administered chitosan and PEG coated PLGA nanoparticles

    SciTech Connect

    Semete, B.; Booysen, L.I.J.; Kalombo, L.; Venter, J.D.; Katata, L.; Ramalapa, B.; Verschoor, J.A.; Swai, H.

    2010-12-01

    Nanoparticulate drug delivery systems offer great promise in addressing challenges of drug toxicity, poor bioavailability and non-specificity for a number of drugs. Much progress has been reported for nano drug delivery systems for intravenous administration, however very little is known about the effects of orally administered nanoparticles. Furthermore, the development of nanoparticulate systems necessitates a thorough understanding of the biological response post exposure. This study aimed to elucidate the in vivo uptake of chitosan and polyethylene glycol (PEG) coated Poly, DL, lactic-co-glycolic Acid (PLGA) nanoparticles and the immunological response within 24 h of oral and peritoneal administration. These PLGA nanoparticles were administered orally and peritoneally to female Balb/C mice, they were taken up by macrophages of the peritoneum. When these particles were fluorescently labelled, intracellular localisation was observed. The expression of pro-inflammatory cytokines IL-2, IL-6, IL-12p70 and TNF-{alpha} in plasma and peritoneal lavage was found to remain at low concentration in PLGA nanoparticles treated mice as well as ZnO nanoparticles during the 24 hour period. However, these were significantly increased in lipopolysaccharide (LPS) treated mice. Of these pro-inflammatory cytokines, IL-6 and IL-12p70 were produced at the highest concentration in the positive control group. The anti-inflammatory cytokines IL-10 and chemokines INF-{gamma}, IL-4, IL-5 remained at normal levels in PLGA treated mice. IL-10 and INF-{gamma} were significantly increased in LPS treated mice. MCP-1 was found to be significantly produced in all groups in the first hours, except the saline treated mice. These results provide the first report to detail the induction of cytokine production by PLGA nanoparticles engineered for oral applications.

  13. In vitro evaluation of the genotoxicity of a family of novel MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer and PLGA nanoparticles

    NASA Astrophysics Data System (ADS)

    He, Lili; Yang, Likai; Zhang, Zhi-rong; Gong, Tao; Deng, Li; Gu, Zhongwei; Sun, Xun

    2009-11-01

    Despite the booming development of nanoparticle materials for pharmaceutical applications, studies on their genotoxicity are few. In our previous efforts to develop an intravenous nanoparticle material, a family of novel monomethoxy(polyethylene glycol)-poly(D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) polymers was synthesized. The cytotoxicity and genotoxicity of nine kinds of selected blank PELGE and PLGA (poly(D,L-lactic and glycolic acid)) nanoparticles were evaluated using methyl thiazolyl tetrazolium (MTT), micronucleus (MN) and sister chromatid exchange (SCE) assays with or without the addition of a metabolic activation system (S9 mix), using Chinese hamster ovary (CHO) cells. The cytotoxicity of nanoparticles exhibited a dose-dependent response, with a concentration of 5 mg ml-1 being the turning point. The frequencies of MN observed in samples treated with various nanoparticles were not statistically different from those seen in the negative controls in the presence or absence of the S9 mix. Also, no cell cycle delay was observed. The numbers of SCE per cell observed in samples treated with five kinds of PELGE nanoparticles were significantly greater than those found in the negative controls with or without the S9 mix. The discrepancies found in the two assays suggest that the five kinds of nanoparticles may produce only a weakly clastogenic response.

  14. In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters

    NASA Astrophysics Data System (ADS)

    Hu, Yun; Ehrich, Marion; Fuhrman, Kristel; Zhang, Chenming

    2014-08-01

    Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC.

  15. Treating cutaneous squamous cell carcinoma using ALA PLGA nanoparticle-mediated photodynamic therapy in a mouse model

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Wang, Xiuli; Zhao, Feng; Luan, Hansen

    2015-03-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Methods: UV-induced cutaneous SCCs were established in hairless mice. ALA loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results: PLGA NPs could enhance PpIX production in SCC. ALA PLGA NP mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.

  16. Development and optimization of quercetin-loaded PLGA nanoparticles by experimental design

    PubMed Central

    TEFAS, LUCIA RUXANDRA; TOMUŢĂ, IOAN; ACHIM, MARCELA; VLASE, LAURIAN

    2015-01-01

    Background and aims Quercetin is a flavonoid with good antioxidant activity, and exhibits various important pharmacological effects. The aim of the present work was to study the influence of formulation factors on the physicochemical properties of quercetin-loaded polymeric nanoparticles in order to optimize the formulation. Materials and methods The nanoparticles were prepared by the nanoprecipitation method. A 3-factor, 3-level Box-Behnken design was employed in this study considering poly(D,L-lactic-co-glycolic) acid (PLGA) concentration, polyvinyl alcohol (PVA) concentration and the stirring speed as independent variables. The responses were particle size, polydispersity index, zeta potential and encapsulation efficiency. Results The PLGA concentration seemed to be the most important factor influencing quercetin-nanoparticle characteristics. Increasing PLGA concentration led to an increase in particle size, as well as encapsulation efficiency. On the other hand, it exhibited a negative influence on the polydispersity index and zeta potential. The PVA concentration and the stirring speed had only a slight influence on particle size and polydispersity index. However, PVA concentration had an important negative effect on the encapsulation efficiency. Based on the results obtained, an optimized formulation was prepared, and the experimental values were comparable to the predicted ones. Conclusions The overall results indicated that PLGA concentration was the main factor influencing particle size, while entrapment efficiency was predominantly affected by the PVA concentration. PMID:26528074

  17. Lactosylated PLGA nanoparticles containing ϵ-polylysine for the sustained release and liver-targeted delivery of the negatively charged proteins.

    PubMed

    Zhou, Ping; An, Tong; Zhao, Chuan; Li, Yuan; Li, Rongshan; Yang, Rui; Wang, Yinsong; Gao, Xiujun

    2015-01-30

    The acidic internal pH environment, initial burst release and lack of targeting property are main limitations of poly(lactide-co-glycolide) (PLGA) nanoparticles for carrying proteins. In this study, ϵ-polylysine (ϵ-PL) was used as an anti-acidic agent and a protein protectant to prepare PLGA nanoparticles for the protein delivery. To obtain the liver-targeting capability, lactosylated PLGA (Lac-PLGA) was synthesized by conjugation of lactose acid to PLGA at both ends, and then used to prepare nanoparticles containing ϵ-PL by the nanoprecipitation method. Bovine serumal bumin (BSA), a negatively charged protein, was efficiently loaded into Lac-PLGA/ϵ-PL nanoparticles and exhibited significant decreased burst release in vitro, sustained release in the blood and increased liver distribution in mice after intravenous injections. The enhanced stability of BSA was due to its electrical interaction with ϵ-PL and the neutralized internal environment of nanoparticles. In conclusion, Lac-PLGA/ϵ-PL nanoparticle system can be used as a promising carrier for the negatively charged proteins.

  18. 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

  19. Enhanced singlet oxygen generation from PLGA loaded with verteporfin and gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Deng, Wei; Kautzka, Zofia; Goldys, Ewa M.

    2016-12-01

    In this study, poly(lactic-co-glycolic acid) (PLGA) nanocomposites were developed by incorporating a photosensitizer, verteporfin and gold nanoparticles into this polymeric matrix and utilised for enhanced photoynamic therapy. Both enhanced fluorescence and singlet oxygen generation from verteporfin were observed in this new formulation under both 425nm LED and 405nm laser illumination. A maximum enhancement factor of 2.5 for fluorescence and 1.84 for 1O2 generation was obtained when the molar ratio of gold:VP was 5:1 and excited at 425 nm, compared with PLGA doped with verteporfin only. The experiment results could be explained by the local electric field enhancement of gold nanoparticles. Furthermore, in vitro cell-killing effect on human pancreatic cancer cells was also demonstrated by using this new formulation following light exposure, indicating the utility of these nanocomposites for enhanced photodynamic therapy.

  20. In Vitro Evaluation of the Biological Responses of Canine Macrophages Challenged with PLGA Nanoparticles Containing Monophosphoryl Lipid A

    PubMed Central

    Guldner, Delphine; Hwang, Julianne K.; Cardieri, Maria Clara D.; Eren, Meaghan; Ziaei, Parissa; Norton, M. Grant; Souza, Cleverson D.

    2016-01-01

    Poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been considerably studied as a promising biodegradable delivery system to induce effective immune responses and to improve stability, safety, and cost effectiveness of vaccines. The study aimed at evaluating early inflammatory effects and cellular safety of PLGA NPs, co-encapsulating ovalbumin (PLGA/OVA NPs), as a model antigen and the adjuvant monophosphoryl lipid A (PLGA/MPLA NPs) as an adjuvant, on primary canine macrophages. The PLGA NPs constructs were prepared following the emulsion-solvent evaporation technique and further physic-chemically characterized. Peripheral blood mononuclear cells were isolated from canine whole blood by magnetic sorting and further cultured to generate macrophages. The uptake of PLGA NP constructs by macrophages was demonstrated by flow cytometry, transmission electron microscopy and confocal microscopy. Macrophage viability and morphology were evaluated by trypan blue exclusion and light microscopy. Macrophages were immunophenotyped for the expression of MHC-I and MHC-II and gene expression of Interleukin-10 (IL-10), Interleukin-12 (IL-12p40), and tumor necrosis factor alpha (TNF-α) were measured. The results showed that incubation of PLGA NP constructs with macrophages revealed effective early uptake of the PLGA NPs without altering the viability of macrophages. PLGA/OVA/MPLA NPs strongly induced TNF-α and IL-12p40 expression by macrophages as well as increase relative expression of MHC-I but not MHC-II molecules. Taken together, these results indicated that PLGA NPs with addition of MPLA represent a good model, when used as antigen carrier, for further, in vivo, work aiming to evaluate their potential to induce strong, specific, immune responses in dogs. PMID:27835636

  1. Impact of PEG and PEG-b-PAGE modified PLGA on nanoparticle formation, protein loading and release.

    PubMed

    Rietscher, René; Czaplewska, Justyna A; Majdanski, Tobias C; Gottschaldt, Michael; Schubert, Ulrich S; Schneider, Marc; Lehr, Claus-Michael

    2016-03-16

    The effect of modifying the well-established pharmaceutical polymer PLGA by different PEG-containing block-copolymers on the preparation of ovalbumin (OVA) loaded PLGA nanoparticles (NPs) was studied. The used polymers contained poly(d,l-lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG) and poly(allyl glycidyl ether) (PAGE) as building blocks. The double emulsion technique yielded spherical NPs in the size range from 170 to 220 nm (PDI<0.15) for all the differently modified polymers, allowing to directly compare protein loading of and release. PEGylation is usually believed to increase the hydrophilic character of produced particles, favoring encapsulation of hydrophilic substances. However, in this study simple PEGylation of PLGA had only a slight effect on protein release. In contrast, incorporating a PAGE block between the PEG and PLGA units, also eventually enabling active targeting introducing a reactive group, led to a significantly higher loading (+25%) and release rate (+100%), compared to PLGA and PEG-b-PLGA NPs.

  2. Cationic nanoparticles with quaternary ammonium-functionalized PLGA-PEG-based copolymers for potent gene transfection

    NASA Astrophysics Data System (ADS)

    Wang, Yan-Hsung; Fu, Yin-Chih; Chiu, Hui-Chi; Wang, Chau-Zen; Lo, Shao-Ping; Ho, Mei-Ling; Liu, Po-Len; Wang, Chih-Kuang

    2013-11-01

    The objective of the present work was to develop new cationic nanoparticles (cNPs) with amphiphilic cationic copolymers for the delivery of plasmid DNA (pDNA). Cationic copolymers were built on the synthesis of quaternary ammonium salt compounds from diethylenetriamine (DETA) to include the positively charged head group and amphiphilic multi-grafts. PLGA- phe-PEG- qDETA (PPD), phe-PEG- qDETA-PLGA (PDP), and PLGA- phe-PEG- qDETA-PLGA (PPDP) cationic copolymers were created by this moiety of DETA quaternary ammonium, heterobifunctional polyethylene glycol (COOH-PEG-NH2), phenylalanine ( phe), and poly(lactic- co-glycolic acid) (PLGA). These new cNPs were prepared by the water miscible solvent displacement method. They exhibit good pDNA binding ability, as shown in a retardation assay that occurred at a particle size of 217 nm. The zeta potential was approximately +21 mV when the cNP concentration was 25 mg/ml. The new cNPs also have a better buffering capacity than PLGA NPs. However, the pDNA binding ability was demonstrated starting at a weight ratio of approximately 6.25 cNPs/pDNA. Gene transfection results showed that these cNPs had transfection effects similar to those of Lipofectamine 2000 in 293T cells. Furthermore, cNPs can also transfect human adipose-derived stem cells. The results indicate that the newly developed cNP is a promising candidate for a novel gene delivery vehicle.

  3. Optical barcoding of PLGA for multispectral analysis of nanoparticle fate in vivo.

    PubMed

    Medina, David X; Householder, Kyle T; Ceton, Ricki; Kovalik, Tina; Heffernan, John M; Shankar, Rohini V; Bowser, Robert P; Wechsler-Reya, Robert J; Sirianni, Rachael W

    2017-03-03

    Understanding of the mechanisms by which systemically administered nanoparticles achieve delivery across biological barriers remains incomplete, due in part to the challenge of tracking nanoparticle fate in the body. Here, we develop a new approach for "barcoding" nanoparticles composed of poly(lactic-co-glycolic acid) (PLGA) with bright, spectrally defined quantum dots (QDs) to enable direct, fluorescent detection of nanoparticle fate with subcellular resolution. We show that QD labeling does not affect major biophysical properties of nanoparticles or their interaction with cells and tissues. Live cell imaging enabled simultaneous visualization of the interaction of control and targeted nanoparticles with bEnd.3 cells in a flow chamber, providing direct evidence that surface modification of nanoparticles with the cell-penetrating peptide TAT increases their biophysical association with cell surfaces over very short time periods under convective current. We next developed this technique for quantitative biodistribution analysis in vivo. These studies demonstrate that nanoparticle surface modification with the cell penetrating peptide TAT facilitates brain-specific delivery that is restricted to brain vasculature. Although nanoparticle entry into the healthy brain parenchyma is minimal, with no evidence for movement of nanoparticles across the blood-brain barrier (BBB), we observed that nanoparticles are able to enter to the central nervous system (CNS) through regions of altered BBB permeability - for example, into circumventricular organs in the brain or leaky vasculature of late-stage intracranial tumors. In sum, these data demonstrate a new, multispectral approach for barcoding PLGA, which enables simultaneous, quantitative analysis of the fate of multiple nanoparticle formulations in vivo.

  4. Immune responses to vaccines delivered by encapsulation into and/or adsorption onto cationic lipid-PLGA hybrid nanoparticles.

    PubMed

    Liu, Lanxia; Ma, Pingchuan; Wang, Hai; Zhang, Chao; Sun, Hongfan; Wang, Chun; Song, Cunxian; Leng, Xigang; Kong, Deling; Ma, Guilei

    2016-03-10

    In this study, we used cationic lipid-poly(lactide-co-glycolide) acid (PLGA) hybrid nanoparticles as antigen delivery carriers to investigate how antigen-loading methods affect antigen exposure to the immune system and evaluated the resulting antigen-specific immune responses. We formulated three classes of antigen adsorbed and/or encapsulated cationic lipid-PLGA hybrid nanoparticles; we designated antigen-adsorbed (out), antigen-encapsulated (in), and antigen-adsorbed/encapsulated (both) nanoparticles. Our results demonstrate significantly more efficient lysosomal escape and cross-presentation of antigen from dendritic cells (DCs) that were exposed to "both" and "in" nanoparticles. In vivo experiments further revealed that "both" nanoparticles significantly more effectively provided not only adequate initial antigen exposure but also long-term antigen persistence at the injection site. Data from flow cytometry and ELISA analyses demonstrated elevated in vivo immune responses from mice that were immunized with nanoparticles-delivered OVA when compared with free OVA. In addition, "in" and "both" nanoparticles elicited significantly higher antigen-specific immune response than "out" nanoparticles and free OVA. These results suggest that the location of antigen entrapment is an important factor in modulating the immune responses of antigens delivered by nanoparticles. Overall, we propose here a promising approach for the future design of vaccines using cationic lipid-PLGA nanoparticles.

  5. Preparation and in vitro evaluation of thienorphine-loaded PLGA nanoparticles.

    PubMed

    Yang, Yang; Xie, Xiang Yang; Mei, Xing Guo

    2016-01-01

    Poly (d,l-lactic-co-glycolide) nanoparticles (PLGA-NPs) have attracted considerable interest as new delivery vehicles for small molecules, with the potential to overcome issue such as poor drug solubility and cell permeability. However, their negative surface charge decreases bioavailability under oral administration. Recently, cationically modified PLGA-NPs has been introduced as novel carriers for oral delivery. In this study, our aim was to introduce and evaluate the physiochemical characteristics and bioadhesion of positively charged chitosan-coated PLGA-NPs (CS-PLGA-NPs), using thienorphine as a model drug. These results indicated that both CS-PLGA-NPs and PLGA-NPs had a narrow size distribution, averaging less than 130 nm. CS-PLGA-NPs was positively charged (+42.1 ± 0.4 mV), exhibiting the cationic nature of chitosan, whereas PLGA-NPs showed a negative surface charge (-2.01 ± 0.3 mV). CS-PLGA-NPs exhibited stronger bioadhesive potency than PLGA-NPs. Furthermore, the transport of thienorphine-CS-PLGA-NPs by Caco-2 cells was higher than thienorphine-PLGA-NPs or thienorphine solution. CS-PLGA-NPs were also found to significantly enhance cellular uptake compared with PLGA-NPs on Caco-2 cells. An evaluation of cytotoxicity showed no increase in toxicity in either kind of nanoparticles during the formulation process. The study proves that CS-PLGA-NPs can be used as a vector in oral drug delivery systems for thienorphine due to its positive surface charge and bioadhesive properties.

  6. Interactions of PLGA nanoparticles with blood components: protein adsorption, coagulation, activation of the complement system and hemolysis studies

    NASA Astrophysics Data System (ADS)

    Fornaguera, Cristina; Calderó, Gabriela; Mitjans, Montserrat; Vinardell, Maria Pilar; Solans, Conxita; Vauthier, Christine

    2015-03-01

    The intravenous administration of poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been widely reported as a promising alternative for delivery of drugs to specific cells. However, studies on their interaction with diverse blood components using different techniques are still lacking. Therefore, in the present work, the interaction of PLGA nanoparticles with blood components was described using different complementary techniques. The influence of different encapsulated compounds/functionalizing agents on these interactions was also reported. It is worth noting that all these techniques can be simply performed, without the need for highly sophisticated apparatus or skills. Moreover, their transference to industries and application of quality control could be easily performed. Serum albumin was adsorbed onto all types of tested nanoparticles. The saturation concentration was dependent on the nanoparticle size. In contrast, fibrinogen aggregation was dependent on nanoparticle surface charge. The complement activation was also influenced by the nanoparticle functionalization; the presence of a functionalizing agent increased complement activation, while the addition of an encapsulated compound only caused a slight increase. None of the nanoparticles influenced the coagulation cascade at low concentrations. However, at high concentrations, cationized nanoparticles did activate the coagulation cascade. Interactions of nanoparticles with erythrocytes did not reveal any hemolysis. Interactions of PLGA nanoparticles with blood proteins depended both on the nanoparticle properties and the protein studied. Independent of their loading/surface functionalization, PLGA nanoparticles did not influence the coagulation cascade and did not induce hemolysis of erythrocytes; they could be defined as safe concerning induction of embolization and cell lysis.The intravenous administration of poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been widely reported as a promising

  7. TPGS2k/PLGA nanoparticles for overcoming multidrug resistance by interfering mitochondria of human alveolar adenocarcinoma cells.

    PubMed

    Wang, Dong-Fang; Rong, Wen-Ting; Lu, Yu; Hou, Jie; Qi, Shan-Shan; Xiao, Qing; Zhang, Jue; You, Jin; Yu, Shu-Qin; Xu, Qian

    2015-02-25

    In this study, we successfully synthesized d-α-tocopheryl polyethylene glycol 2000 succinate (TPGS2k) and prepared TPGS2k-modified poly(lactic-co-glycolic acid) nanoparticles (TPGS2k/PLGA NPs) loaded with 7-ethyl-10-hydroxycamptothecin (SN-38), designated TPGS2k/PLGA/SN-38 NPs. Characterization measurements showed that TPGS2k/PLGA/SN-38 NPs displayed flat and spheroidal particles with diameters of 80-104 nm. SN-38 was encapsulated in TPGS2k emulsified PLGA NPs with the entrapment efficiency and loading rates of SN-38 83.6 and 7.85%, respectively. SN-38 could release constantly from TPGS2k/PLGA/SN-38 NPs in vitro. TPGS2k/PLGA/SN-38 NPs induced significantly higher cytotoxicity on A549 cells and the multidrug resistance (MDR) cell line (A549/DDP cells and A549/Taxol cells) compared with free SN-38. Further studies on the mechanism of the NPs in increasing the death of MDR cells showed that following the SN-38 releasing into cytoplasm the remaining TPGS2k/PLGA NPs could reverse the P-gp mediated MDR via interfering with the structure and function of mitochondria and rather than directly inhibiting the enzymatic activity of P-gp ATPase. Therefore, TPGS2k/PLGA NPs can reduce the generation of ATP and the release of energy for the requisite of P-gp efflux transporters. The results indicated that TPGS2k/PLGA NPs could become the nanopharmaceutical materials with the capability to reversal MDR and improve anticancer effects of some chemotherapy drugs as P-gp substrates.

  8. PLGA nanoparticle encapsulation reduces toxicity while retaining the therapeutic efficacy of EtNBS-PDT in vitro

    PubMed Central

    Hung, Hsin-I; Klein, Oliver J.; Peterson, Sam W.; Rokosh, Sarah R.; Osseiran, Sam; Nowell, Nicholas H.; Evans, Conor L.

    2016-01-01

    Photodynamic therapy regimens, which use light-activated molecules known as photosensitizers, are highly selective against many malignancies and can bypass certain challenging therapeutic resistance mechanisms. Photosensitizers such as the small cationic molecule EtNBS (5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium chloride) have proven potent against cancer cells that reside within acidic and hypoxic tumour microenvironments. At higher doses, however, these photosensitizers induce “dark toxicity” through light-independent mechanisms. In this study, we evaluated the use of nanoparticle encapsulation to overcome this limitation. Interestingly, encapsulation of the compound within poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-EtNBS) was found to significantly reduce EtNBS dark toxicity while completely retaining the molecule’s cytotoxicity in both normoxic and hypoxic conditions. This dual effect can be attributed to the mechanism of release: EtNBS remains encapsulated until external light irradiation, which stimulates an oxygen-independent, radical-mediated process that degrades the PLGA nanoparticles and releases the molecule. As these PLGA-encapsulated EtNBS nanoparticles are capable of penetrating deeply into the hypoxic and acidic cores of 3D spheroid cultures, they may enable the safe and efficacious treatment of otherwise unresponsive tumour regions. PMID:27686626

  9. PLGA nanoparticle encapsulation reduces toxicity while retaining the therapeutic efficacy of EtNBS-PDT in vitro

    NASA Astrophysics Data System (ADS)

    Hung, Hsin-I.; Klein, Oliver J.; Peterson, Sam W.; Rokosh, Sarah R.; Osseiran, Sam; Nowell, Nicholas H.; Evans, Conor L.

    2016-09-01

    Photodynamic therapy regimens, which use light-activated molecules known as photosensitizers, are highly selective against many malignancies and can bypass certain challenging therapeutic resistance mechanisms. Photosensitizers such as the small cationic molecule EtNBS (5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium chloride) have proven potent against cancer cells that reside within acidic and hypoxic tumour microenvironments. At higher doses, however, these photosensitizers induce “dark toxicity” through light-independent mechanisms. In this study, we evaluated the use of nanoparticle encapsulation to overcome this limitation. Interestingly, encapsulation of the compound within poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-EtNBS) was found to significantly reduce EtNBS dark toxicity while completely retaining the molecule’s cytotoxicity in both normoxic and hypoxic conditions. This dual effect can be attributed to the mechanism of release: EtNBS remains encapsulated until external light irradiation, which stimulates an oxygen-independent, radical-mediated process that degrades the PLGA nanoparticles and releases the molecule. As these PLGA-encapsulated EtNBS nanoparticles are capable of penetrating deeply into the hypoxic and acidic cores of 3D spheroid cultures, they may enable the safe and efficacious treatment of otherwise unresponsive tumour regions.

  10. A small variation in average particle size of PLGA nanoparticles prepared by nanoprecipitation leads to considerable change in nanoparticles' characteristics and efficacy of intracellular delivery.

    PubMed

    Sahin, Adem; Esendagli, Gunes; Yerlikaya, Firat; Caban-Toktas, Secil; Yoyen-Ermis, Digdem; Horzum, Utku; Aktas, Yesim; Khan, Mansoor; Couvreur, Patrick; Capan, Yilmaz

    2017-01-13

    In this study, it was aimed to investigate characteristics and intracellular delivery of two different-sized PLGA nanoparticles in ouzo region by considering number of nanoparticles. To determine the effect of formulation parameters on average particle size, Dil labeled nanoparticles were prepared using a three-factor, two-level full factorial statistical experimental design. PLGA230 (230.8 ± 4.32 nm) and PLGA160 (157.9 ± 6.16 nm) nanoparticles were obtained by altering polymer amount based on experimental design results and characterized. Same number of PLGA230 and PLGA160 nanoparticles per cell were applied onto HEK293 cells; then, cytotoxicity, uptake kinetics and mechanism were evaluated by flow cytometry and fluorescent microscopy. Also same weight of PLGA230 and PLGA160 nanoparticles were applied and cellular uptake of these nanoparticles was evaluated. It was found that PLGA230 nanoparticles had higher encapsulation efficiency and slower dye release compared to PLGA160 nanoparticles. When they were applied at same counts per cell, PLGA230 nanoparticles displayed faster and higher intracellular dye transfer than PLGA160 nanoparticles. On the other hand, PLGA160 appeared to be a more effective vehicle than PLGA230 when applied at the same weight concentration. It was also shown that for both nanoparticles, HEK293 cells employed macropinocytic, caveolae- and clathrin-mediated endocytic pathways.

  11. Neoangiogenesis of human mesenchymal stem cells transfected with peptide-loaded and gene-coated PLGA nanoparticles.

    PubMed

    Park, Ji Sun; Yang, Han Na; Yi, Se Won; Kim, Jae-Hwan; Park, Keun-Hong

    2016-01-01

    Several factors are involved in angiogenesis. To form new blood vessels, we fabricated vehicles carrying an angiogenesis-related peptide (apelin) and gene (vascular endothelial growth factor (VEGF)165) that were internalized by human mesenchymal stem cells (hMSCs). These non-toxic poly-(DL)-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) easily entered hMSCs without cytotoxicity. The negatively charged outer surface of PLGA NPs can be easily complexed with highly positively charged polyethylenimine (PEI) to deliver genes into cells. PLGA NPs complexed with PEI could be coated with negatively charged VEGF plasmid DNA and loaded with apelin. The physical characteristics of these PLGA NPs were determined by size distribution, gel retardation, and morphological analyses. Transfection of VEGF-coated apelin-loaded PLGA NPs resulted in the differentiation of hMSCs into endothelial cells and vascular formation in Matrigel in vitro. Following injection of hMSCs transfected with these PLGA NPs into an ischemic hind limb mouse model, these cells differentiated into endothelial cells and accelerated neovascularization.

  12. Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles.

    PubMed

    Sharma, Deepak; Sharma, Rakesh Kumar; Sharma, Navneet; Gabrani, Reema; Sharma, Sanjeev K; Ali, Javed; Dang, Shweta

    2015-10-01

    The objective of the present investigation was to optimize diazepam (Dzp)-loaded poly(lactic-co-glycolic acid) nanoparticles (NP) to achieve delivery in the brain through intranasal administration. Dzp nanoparticles (DNP) were formulated by nanoprecipitation and optimized using Box-Behnken design. The influence of various independent process variables (polymer, surfactant, aqueous to organic (w/o) phase ratio, and drug) on resulting properties of DNP (z-average and drug entrapment) was investigated. Developed DNP showed z-average 148-337 d.nm, polydispersity index 0.04-0.45, drug entrapment 69-92%, and zeta potential in the range of -15 to -29.24 mV. Optimized DNP were further analyzed by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), ex-vivo drug release, and in-vitro cytotoxicity. Ex-vivo drug release study via sheep nasal mucosa from DNP showed a controlled release of 64.4% for 24 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay performed on Vero cell line showed less toxicity for DNP as compared to Dzp suspension (DS). Gamma scintigraphy and biodistribution study of DNP and DS was performed on Sprague-Dawley rats using technetium-99m-labeled ((99m)Tc) Dzp formulations to investigate the nose-to-brain drug delivery pathway. Brain/blood uptake ratios, drug targeting efficiency, and direct nose-to-brain transport were found to be 1.23-1.45, 258, and 61% for (99m)Tc-DNP (i.n) compared to (99m)Tc-DS (i.n) (0.38-1.06, 125, and 1%). Scintigraphy images showed uptake of Dzp from nose-to-brain, and this observation was in agreement with the biodistribution results. These results suggest that the developed poly(D,L-lactide-co-glycolide) (PLGA) NP could serve as a potential carrier of Dzp for nose-to-brain delivery in outpatient management of status epilepticus.

  13. Fabrication and in vivo evaluation of Nelfinavir loaded PLGA nanoparticles for enhancing oral bioavailability and therapeutic effect

    PubMed Central

    Venkatesh, D. Nagasamy; Baskaran, Mahendran; Karri, Veera Venkata Satyanarayana Reddy; Mannemala, Sai Sandeep; Radhakrishna, Kollipara; Goti, Sandip

    2015-01-01

    Nelfinavir mesylate (NFV) is an anti-viral drug, used in the treatment of Acquired Immunodeficiency Syndrome (AIDS). Poor oral bioavailability and shorter half-life (3.5–5 h) remain a major clinical limitation of NFV leading to unpredictable drug bioavailability and frequent dosing. In this context, the objective of the present study was to formulate NFV loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which can increase the solubility and oral bioavailability along with sustained release of the drug. NFV loaded PLGA-NPs were prepared by nanoprecipitation method using PLGA and Poloxomer 407. The prepared NPs were evaluated for particle size, zeta potential, morphology, drug content, entrapment efficiency (EE) and in vitro dissolution studies. Oral bioavailability studies were carried out in New Zealand rabbits by administering developed NFV PLGA-NPs and pure drug suspension. PLGA-NPs prepared by using 1:4 ratio of drug and PLGA, with a stirring rate of 1500 rpm for 4 h. The prepared NPs were in the size of 185 ± 0.83 nm with a zeta potential of 28.7 ± 0.09 mV. The developed NPs were found to be spherical with uniform size distribution. The drug content and EE of the optimized formulation were found to be 36 ± 0.19% and 72 ± 0.47% respectively. After oral administration of NFV PLGA-NPs, the relative bioavailability was enhanced about 4.94 fold compared to NFV suspension as a control. The results describe an effective strategy for oral delivery of NFV loaded PLGA NPs that helps in enhancing bioavailability and reduce the frequency of dosing. PMID:26702262

  14. Magnetic hyperthermia efficiency and 1H-NMR relaxation properties of iron oxide/paclitaxel-loaded PLGA nanoparticles

    NASA Astrophysics Data System (ADS)

    Ruggiero, Maria R.; Geninatti Crich, Simonetta; Sieni, Elisabetta; Sgarbossa, Paolo; Forzan, Michele; Cavallari, Eleonora; Stefania, Rachele; Dughiero, Fabrizio; Aime, Silvio

    2016-07-01

    Magnetic iron oxide nanoparticles (Fe-NPs) can be exploited in biomedicine as agents for magnetic fluid hyperthermia (MFH) treatments and as contrast enhancers in magnetic resonance imaging. New, oleate-covered, iron oxide particles have been prepared either by co-precipitation or thermal decomposition methods and incorporated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-Fe-NPs) to improve their biocompatibility and in vivo stability. Moreover, the PLGA-Fe-NPs have been loaded with paclitaxel to pursue an MFH-triggered drug release. Remarkably, it has been found that the nanoparticle formulations are characterized by peculiar 1H nuclear magnetic relaxation dispersion (NMRD) profiles that directly correlate with their heating potential when exposed to an alternating magnetic field. By prolonging the magnetic field exposure to 30 min, a significant drug release was observed for PLGA-Fe-NPs in the case of the larger-sized magnetic nanoparticles. Furthermore, the immobilization of lipophilic Fe-NPs in PLGA-NPs also made it possible to maintain Néel relaxation as the dominant relaxation contribution in the presence of large iron oxide cores (diameters of 15-20 nm), with the advantage of preserving their efficiency when they are entrapped in the intracellular environment. The results reported herein show that NMRD profiles are a useful tool for anticipating the heating capabilities of Fe-NPs designed for MFH applications.

  15. Effects of ball-milling on PLGA polymer and its implication on lansoprazole-loaded nanoparticles

    PubMed Central

    Shabir, Anjumn; Alhusban, Farhan; Perrie, Yvonne; Mohammed, Afzal R.

    2011-01-01

    PLGA is a biodegradable polymer utilised widely in pharmaceutical research for the encapsulation of a wide range of drugs as nano particulate systems. This study investigates the impact of rotary ball milling on the physical properties of PLGA and its influence on nanoparticle formation prepared using the solvent displacement technique. By applying mechanical stress to the polymer and altering its physical appearance and molecular weight, the loading of lansoprazole within the nanoparticles was increased to 96%, with a reduction in particle size. The results indicate that rotary ball milling significantly reduces particle size, increases lansoprazole loading and improves the release profile for lansoprazole loaded PLGA nanoparticles PMID:24826005

  16. Preparation, characterization and in vivo evaluation of a combination delivery system based on hyaluronic acid/jeffamine hydrogel loaded with PHBV/PLGA blend nanoparticles for prolonged delivery of Teriparatide.

    PubMed

    Bahari Javan, Nika; Montazeri, Hamed; Rezaie Shirmard, Leila; Jafary Omid, Nersi; Barbari, Ghullam Reza; Amini, Mohsen; Ghahremani, Mohammad Hossein; Rafiee-Tehrani, Morteza; Abedin Dorkoosh, Farid

    2017-04-01

    In the current study, biodegradable PHBV/PLGA blend nanoparticles (NPs) containing Teriparatide were loaded in hyaluronic acid/jeffamine (HA-JEF ED-600) hydrogel to prepare a combination delivery system (CDS) for prolonged delivery of Teriparatide. The principal purpose of the present study was to formulate an effective and prolonged Teriparatide delivery system in order to reduce the frequency of injection and thus enhance patient's compliance. Morphological properties, swelling behaviour, crosslinking efficiency and rheological characterization of HA-JEF ED-600 hydrogel were evaluated. The CDS was acquired by adding PHBV/PLGA NPs to HA-JEF ED-600 hydrogel simultaneously with crosslinking reaction. The percentage of NPs incorporation within the hydrogel as well as the loading capacity and morphology of Teriparatide loaded CDS were examined. Intrinsic fluorescence and circular dichroism spectroscopy proved that Teriparatide remains stable after processing. The release profile represented 63% Teriparatide release from CDS within 50days with lower burst release compared to NPs and hydrogel. MTT assay was conducted by using NIH3T3 cell line and no sign of reduction in cell viability was observed. Based on Miller and Tainter method, LD50 of Teriparatide loaded CDS was 131.8mg/kg. In vivo studies demonstrated that Teriparatide loaded CDS could effectively increase serum calcium level after subcutaneous injection in mice. Favourable results in the current study introduced CDS as a promising candidate for controlled delivery of Teriparatide and pave the way for future investigations in the field of designing prolonged delivery systems for other peptides and proteins.

  17. Development of sulfadiazine-decorated PLGA nanoparticles loaded with 5-fluorouracil and cell viability.

    PubMed

    Guimarães, Pedro Pires Goulart; Oliveira, Sheila Rodrigues; de Castro Rodrigues, Gabrielle; Gontijo, Savio Morato Lacerda; Lula, Ivana Silva; Cortés, Maria Esperanza; Denadai, Ângelo Márcio Leite; Sinisterra, Rubén Dario

    2015-01-08

    The aim of this work was to synthesize sulfadiazine-poly(lactide-co-glycolide) (SUL-PLGA) nanoparticles (NPs) for the efficient delivery of 5-fluorouracil to cancer cells. The SUL-PLGA conjugation was assessed using FTIR, 1H-NMR, 13C-NMR, elemental analysis and TG and DTA analysis. The SUL-PLGA NPs were characterized using transmission and scanning electron microscopy and dynamic light scattering. Additionally, the zeta potential, drug content, and in vitro 5-FU release were evaluated. We found that for the SUL-PLGA NPs, Dh = 114.0 nm, ZP = -32.1 mV and the encapsulation efficiency was 49%. The 5-FU was released for up to 7 days from the NPs. Cytotoxicity evaluations of 5-FU-loaded NPs (5-FU-SUL-PLGA and 5-FU-PLGA) on two cancer cell lines (Caco-2, A431) and two normal cell lines (fibroblast, osteoblast) were compared. Higher cytotoxicity of 5-FU-SUL-PLGA NPs were found to both cancer cell lines when compared to normal cell lines, demonstrating that the presence of SUL could significantly enhance the cytotoxicity of the 5-FU-SUL-PLGA NPs when compared with 5-FU-PLGA NPs. Thus, the development of 5-FU-SUL-PLGA NPs to cancer cells is a promising strategy for the 5-FU antitumor formulation in the future.

  18. Co-delivery of docetaxel and Poloxamer 235 by PLGA-TPGS nanoparticles for breast cancer treatment.

    PubMed

    Tang, Xiaolong; Liang, Yong; Feng, Xiaojun; Zhang, Rongbo; Jin, Xu; Sun, Leilei

    2015-04-01

    Multidrug resistance (MDR) is a major hurdle to the success of cancer chemotherapy. Poloxamers have been shown to reverse MDR by inhibiting the P-glycoprotein (P-gp) pump. The objective of this research is to test the feasibility of docetaxel-loaded PLGA-TPGS/Poloxamer 235 nanoparticles to overcome MDR in docetaxel-resistant human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by a modified nanoprecipitation method using PLGA-TPGS and PLGA-TPGS/Poloxamer 235 mixture, respectively. The PLGA-TPGS/Poloxamer 235 nanoparticles were of spherical shape and have a rough and porous surface. The docetaxel-loaded PLGA-TPGS/Poloxamer 235 porous nanoparticles which had an average size of around 180nm with a narrow size distribution were stable, showing almost no change in particle size and surface charge during the 3-month storage period. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PLGA-TPGS/Poloxamer 235 porous nanoparticles (PPNPs) in docetaxel-resistant human breast cancer cell line, MCF-7/TXT, in comparison with PLGA-TPGS nanoparticles (PTNPs). The PLGA-TPGS/Poloxamer 235 porous nanoparticles produced significantly higher level of toxicity than both of PLGA-TPGS nanoparticle formulation and Taxotere® both in vitro and in vivo, indicating docetaxel-loaded PLGA-TPGS/Poloxamer 235 porous nanoparticles have significant potential for the treatment of breast cancer.

  19. Gelsolin Amyloidogenesis Is Effectively Modulated by Curcumin and Emetine Conjugated PLGA Nanoparticles

    PubMed Central

    Goel, Surbhi; Kundu, Bishwajit; Mishra, Prashant; Fnu, Ashish

    2015-01-01

    Small molecule based therapeutic intervention of amyloids has been limited by their low solubility and poor pharmacokinetic characteristics. We report here, the use of water soluble poly lactic-co-glycolic acid (PLGA)-encapsulated curcumin and emetine nanoparticles (Cm-NPs and Em-NPs, respectively), as potential modulators of gelsolin amyloidogenesis. Using the amyloid-specific dye Thioflavin T (ThT) as an indicator along with electron microscopic imaging we show that the presence of Cm-NPs augmented amyloid formation in gelsolin by skipping the pre-fibrillar assemblies, while Em-NPs induced non-fibrillar aggregates. These two types of aggregates differed in their morphologies, surface hydrophobicity and secondary structural signatures, confirming that they followed distinct pathways. In spite of differences, both these aggregates displayed reduced toxicity against SH-SY5Y human neuroblastoma cells as compared to control gelsolin amyloids. We conclude that the cytotoxicity of gelsolin amyloids can be reduced by either stalling or accelerating its fibrillation process. In addition, Cm-NPs increased the fibrillar bulk while Em-NPs defibrillated the pre-formed gelsolin amyloids. Moreover, amyloid modulation happened at a much lower concentration and at a faster rate by the PLGA encapsulated compounds as compared to their free forms. Thus, besides improving pharmacokinetic and biocompatible properties of curcumin and emetine, PLGA conjugation elevates the therapeutic potential of both small molecules against amyloid fibrillation and toxicity. PMID:25996685

  20. N-trimethyl chitosan chloride-coated PLGA nanoparticles overcoming multiple barriers to oral insulin absorption.

    PubMed

    Sheng, Jianyong; Han, Limei; Qin, Jing; Ru, Ge; Li, Ruixiang; Wu, Lihong; Cui, Dongqi; Yang, Pei; He, Yuwei; Wang, Jianxin

    2015-07-22

    Although several strategies have been applied for oral insulin delivery to improve insulin bioavailability, little success has been achieved. To overcome multiple barriers to oral insulin absorption simultaneously, insulin-loaded N-trimethyl chitosan chloride (TMC)-coated polylactide-co-glycoside (PLGA) nanoparticles (Ins TMC-PLGA NPs) were formulated in our study. The Ins TMC-PLGA NPs were prepared using the double-emulsion solvent evaporation method and were characterized to determine their size (247.6 ± 7.2 nm), ζ-potential (45.2 ± 4.6 mV), insulin-loading capacity (7.8 ± 0.5%) and encapsulation efficiency (47.0 ± 2.9%). The stability and insulin release of the nanoparticles in enzyme-containing simulated gastrointestinal fluids suggested that the TMC-PLGA NPs could partially protect insulin from enzymatic degradation. Compared with unmodified PLGA NPs, the positively charged TMC-PLGA NPs could improve the mucus penetration of insulin in mucus-secreting HT29-MTX cells, the cellular uptake of insulin via clathrin- or adsorption-mediated endocytosis in Caco-2 cells and the permeation of insulin across a Caco-2 cell monolayer through tight junction opening. After oral administration in mice, the TMC-PLGA NPs moved more slowly through the gastrointestinal tract compared with unmodified PLGA NPs, indicating the mucoadhesive property of the nanoparticles after TMC coating. Additionally, in pharmacological studies in diabetic rats, orally administered Ins TMC-PLGA NPs produced a stronger hypoglycemic effect, with 2-fold higher relative pharmacological availability compared with unmodified NPs. In conclusion, oral insulin absorption is improved by TMC-PLGA NPs with the multiple absorption barriers overcome simultaneously. TMC-PLGA NPs may be a promising drug delivery system for oral administration of macromolecular therapeutics.

  1. Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma.

    PubMed

    Arshad, Azeem; Yang, Bin; Bienemann, Alison S; Barua, Neil U; Wyatt, Marcella J; Woolley, Max; Johnson, Dave E; Edler, Karen J; Gill, Steven S

    2015-01-01

    We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas.

  2. Novel PLGA-based nanoparticles for the oral delivery of insulin

    PubMed Central

    Malathi, Sampath; Nandhakumar, Perumal; Pandiyan, Velayudham; Webster, Thomas J; Balasubramanian, Sengottuvelan

    2015-01-01

    Background Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of D-α-tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was investigated for sustained delivery of insulin (IS). Objective To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin. Methods A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water–oil–water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration. Results The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6%±1.2%, and the mean diameter of the NPs was 180±20 nm. The serum glucose level was significantly (twofold) decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30) NPs when compared to that of free insulin-treated diabetic rats. The results show that the oral administration of ISTPPLG6 NPs is an effective method of reducing serum glucose level for a period of 24 hours. Histopathological studies reveal that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver, kidneys, and pancreas, indicating its biocompatibility and regenerative effects. Conclusion ISTPPLG6 NPs can

  3. Colonic gene silencing using siRNA-loaded calcium phosphate/PLGA nanoparticles ameliorates intestinal inflammation in vivo.

    PubMed

    Frede, Annika; Neuhaus, Bernhard; Klopfleisch, Robert; Walker, Catherine; Buer, Jan; Müller, Werner; Epple, Matthias; Westendorf, Astrid M

    2016-01-28

    Cytokines and chemokines are predominant players in the progression of inflammatory bowel diseases. While systemic neutralization of these players with antibodies works well in some patients, serious contraindications and side effects have been reported. Therefore, the local interference of cytokine signaling mediated by siRNA-loaded nanoparticles might be a promising new therapeutic approach. In this study, we produced multi-shell nanoparticles consisting of a calcium phosphate (CaP) core coated with siRNA directed against pro-inflammatory mediators, encapsulated into poly(d,l-lactide-co-glycolide acid) (PLGA), and coated with a final outer layer of polyethyleneimine (PEI), for the local therapeutic treatment of colonic inflammation. In cell culture, siRNA-loaded CaP/PLGA nanoparticles exhibited a rapid cellular uptake, almost no toxicity, and an excellent in vitro gene silencing efficiency. Importantly, intrarectal application of these nanoparticles loaded with siRNA directed against TNF-α, KC or IP-10 to mice suffering from dextran sulfate sodium (DSS)-induced colonic inflammation led to a significant decrease of the target genes in colonic biopsies and mesenteric lymph nodes which was accompanied with a distinct amelioration of intestinal inflammation. Thus, this study provides evidence that the specific and local modulation of the inflammatory response by CaP/PLGA nanoparticle-mediated siRNA delivery could be a promising approach for the treatment of intestinal inflammation.

  4. A Novel Method for Preparing Surface-Modified Fluocinolone Acetonide Loaded PLGA Nanoparticles for Ocular Use: In Vitro and In Vivo Evaluations.

    PubMed

    Salama, Alaa H; Mahmoud, Azza A; Kamel, Rabab

    2016-10-01

    Our objective was to prepare nanoparticulate system using a simple yet attractive innovated method as an ophthalmic delivery system for fluocinolone acetonide to improve its ocular bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by adopting thin film hydration method using PLGA/poloxamer 407 in weight ratios of 1:5 and 1:10. PLGA was used in 75/25 and 50/50 copolymer molar ratio of DL-lactide/glycolide. Results revealed that using PLGA with lower glycolic acid monomer ratio exhibited high particle size (PS), zeta potential (ZP) and drug encapsulation efficiency (EE) values with slow drug release pattern. Also, doubling the drug concentration during nanoparticles preparation ameliorated its EE to reach almost 100%. Furthermore, studies for separating the un-entrapped drug in nanoparticles using centrifugation method at 20,000 rpm for 30 min showed that the separated clear supernatant contained nanoparticles encapsulating an important drug amount. Therefore, separation of un-entrapped drug was carried out by filtrating the preparation using 20-25 μm pore size filter paper to avoid drug loss. Aiming to increase the PLGA nanoparticles mucoadhesion ability, surface modification of selected formulation was done using different amount of stearylamine and chitosan HCl. Nanoparticles coated with 0.1% w/v chitosan HCl attained most suitable results of PS, ZP and EE values as well as high drug release properties. Transmission electron microphotographs illustrated the deposition of chitosan molecules on the nanoparticles surfaces. Pharmacokinetic studies on Albino rabbit's eyes using HPLC indicated that the prepared novel chitosan-coated PLGA nanoparticles subjected to separation by filtration showed rapid and extended drug delivery to the eye.

  5. Cytotoxicity and intracellular fate of PLGA and chitosan-coated PLGA nanoparticles in Madin-Darby bovine kidney (MDBK) and human colorectal adenocarcinoma (Colo 205) cells.

    PubMed

    Trif, Mihaela; Florian, Paula E; Roseanu, Anca; Moisei, Magdalena; Craciunescu, Oana; Astete, Carlos E; Sabliov, Cristina M

    2015-11-01

    Polymeric nanoparticles (NPs) are known to facilitate intracellular uptake of drugs to improve their efficacy, with minimum bioreactivity. The goal of this study was to assess cellular uptake and trafficking of PLGA NPs and chitosan (Chi)-covered PLGA NPs in Madin-Darby bovine kidney (MDBK) and human colorectal adenocarcinoma (Colo 205) cells. Both PLGA and Chi-PLGA NPs were not cytotoxic to the studied cells at concentrations up to 2500 μg/mL. The positive charge conferred by the chitosan deposition on the PLGA NPs improved NPs uptake by MDBK cells. In this cell line, Chi-PLGA NPs colocalized partially with early endosomes compartment and showed a more consistent perinuclear localization than PLGA NPs. Kinetic uptake of PLGA NPs by Colo 205 was slower than that by MDBK cells, detected only at 24 h, exceeding that of Chi-PLGA NPs. This study offers new insights on NP interaction with target cells supporting the use of NPs as novel nutraceuticals/drug delivery systems in metabolic disorders or cancer therapy. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3599-3611, 2015.

  6. Spectral and Spatial Characterization of Protein Loaded PLGA Nanoparticles

    PubMed Central

    Zidan, Ahmed S.; Rahman, Ziyaur; Habib, Muhammad J.; Khan, Mansoor A.

    2011-01-01

    The objective of this study was to evaluate near infrared (NIR) spectroscopy and imaging as approaches to assess drug contents in poly(dl-lactide-co-glycolide) (PLGA) based nanoparticles of a model protein, cyclosporine A (CyA). A 6-factors 12-runs designed set of experiments with Plackett–Burman (PB) screening was applied in order to examine the effects of drug loading (X1), polymer loading (X2), emulsifier concentration (X3), stirring rate (X4), type of organic solvent (X5), and ratio of organic to aqueous phases' volumes (X6), on drug entrapment efficiency (EFF). After omitting the factors with nonsignificant influences on EFF, a reduced mathematical relationship, EFF = 48.34 + 7.3X1 − 29.95X3, was obtained to explain the effect of the significant factors on EFF. Using two different sets for calibration and validation, the developed NIR calibration model was able to assess CyA contents within the 12 PB formulations. NIR spectral imaging was capable of clearly distinguishing the 12 formulations, both qualitatively and quantitatively. A good correlation with a coefficient of 0.9727 was obtained for constructing a quantile-quantile plot for the actual drug loading percentage and the % standard deviation obtained for the drug loading prediction using the hyperspectral images. PMID:19774658

  7. Endocytosis of Nanomedicines: The Case of Glycopeptide Engineered PLGA Nanoparticles

    PubMed Central

    Vilella, Antonietta; Ruozi, Barbara; Belletti, Daniela; Pederzoli, Francesca; Galliani, Marianna; Semeghini, Valentina; Forni, Flavio; Zoli, Michele; Vandelli, Maria Angela; Tosi, Giovanni

    2015-01-01

    The success of nanomedicine as a new strategy for drug delivery and targeting prompted the interest in developing approaches toward basic and clinical neuroscience. Despite enormous advances on brain research, central nervous system (CNS) disorders remain the world’s leading cause of disability, in part due to the inability of the majority of drugs to reach the brain parenchyma. Many attempts to use nanomedicines as CNS drug delivery systems (DDS) were made; among the various non-invasive approaches, nanoparticulate carriers and, particularly, polymeric nanoparticles (NPs) seem to be the most interesting strategies. In particular, the ability of poly-lactide-co-glycolide NPs (PLGA-NPs) specifically engineered with a glycopeptide (g7), conferring to NPs’ ability to cross the blood brain barrier (BBB) in rodents at a concentration of up to 10% of the injected dose, was demonstrated in previous studies using different routes of administrations. Most of the evidence on NP uptake mechanisms reported in the literature about intracellular pathways and processes of cell entry is based on in vitro studies. Therefore, beside the particular attention devoted to increasing the knowledge of the rate of in vivo BBB crossing of nanocarriers, the subsequent exocytosis in the brain compartments, their fate and trafficking in the brain surely represent major topics in this field. PMID:26102358

  8. Samarium oxide as a radiotracer to evaluate the in vivo biodistribution of PLGA nanoparticles

    NASA Astrophysics Data System (ADS)

    Mandiwana, Vusani; Kalombo, Lonji; Venter, Kobus; Sathekge, Mike; Grobler, Anne; Zeevaart, Jan Rijn

    2015-09-01

    Developing nanoparticulate delivery systems that will allow easy movement and localization of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge in nanomedicine. The aim of this study was to evaluate the biodistribution of poly( d, l-lactide- co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([153Sm]Sm2O3) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear reactor to produce radioactive 153Sm-loaded-PLGA nanoparticles. The nanoparticles were characterized for size, zeta potential, and morphology. The nanoparticles were orally and intravenously (IV) administered to rats in order to trace their uptake through imaging and biodistribution studies. The 153Sm-loaded-PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The zeta potential ranged between 5 and 20 mV. The [153Sm]Sm2O3 loaded PLGA nanoparticles, orally administered were distributed to most organs at low levels, indicating that there was absorption of nanoparticles. While the IV injected [153Sm]Sm2O3-loaded PLGA nanoparticles exhibited the highest localization of nanoparticles in the spleen (8.63 %ID/g) and liver (3.07 %ID/g), confirming that nanoparticles are rapidly removed from the blood by the RES, leading to rapid uptake in the liver and spleen. From the biodistribution data obtained, it is clear that polymeric nanoscale delivery systems would be suitable for improving permeability and thus the bioavailability of therapeutic compounds.

  9. Surface modification of PLGA nanoparticles with biotinylated chitosan for the sustained in vitro release and the enhanced cytotoxicity of epirubicin.

    PubMed

    Chen, Hongli; Xie, Li Qin; Qin, Jingwen; Jia, Yajing; Cai, Xinhua; Nan, WenBin; Yang, Wancai; Lv, Feng; Zhang, Qi Qing

    2016-02-01

    In this study, poly(d,l-lactide-co-glycolide) nanoparticles (PLGA NPs) with biotinylated chitosan (Bio-CS)-surface modification were prepared to be usded as a tumor-targeted and prolonged delivery system for anticancer drugs. Epirubicin (EPB), as a model drug, was encapsulated into Bio-CS surface modified PLGA (Bio-CS-PLGA) NPs with a drug encapsulation efficiency of 84.1 ± 3.4%. EPB-loaded Bio-CS-PLGA NPs were spherical shaped, and had a larger size and higher positive zeta potential compared to the unmodfied EPB-loaded PLGA NPs. The in vitro drug releases showed that EPB-loaded Bio-CS-PLGA NPs exhibited relatively constant drug release kinetics during the first 48 h and the drug burst release significantly decreased in comparison to the unmodified PLGA NPs. The results of MTS assays showed that Bio-CS-PLGA NPs markedly increased the cytotoxicity of EPB, compared to both the unmodified PLGA NPs and the CS-PLGA NPs. The uptakes of NPs in human breast cancer MCF-7 cells were evaluated by the flow cytometry and the confocal microscope. The results revealed that Bio-CS-PLGA NPs exhibited a greater extent of cellular uptake than the unmodified PLGA NPs and CS-PLGA NPs. Moreover, the cellular uptake of Bio-CS-PLGA NPs was evidently inhibited by the endocytic inhibitors and the receptor ligand, indicating that biotin receptor-mediated endocytosis was perhaps involved in the cell entry of Bio-CS-PLGA NPs. In MCF-7 tumor-bearing nude mice, EPB-loaded Bio-CS-PLGA NPs were efficiently accumulated in the tumors. In summary, Bio-CS-PLGA NPs displayed great potential for application as the carriers of anticancer drugs.

  10. Delivery of multiple siRNAs using lipid-coated PLGA nanoparticles for treatment of prostate cancer.

    PubMed

    Hasan, Warefta; Chu, Kevin; Gullapalli, Anuradha; Dunn, Stuart S; Enlow, Elizabeth M; Luft, J Christopher; Tian, Shaomin; Napier, Mary E; Pohlhaus, Patrick D; Rolland, Jason P; DeSimone, Joseph M

    2012-01-11

    Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called Particle Replication In Nonwetting Templates (PRINT). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32-46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer.

  11. Delivery of Multiple siRNAs Using Lipid-coated PLGA Nanoparticles for Treatment of Prostate Cancer

    PubMed Central

    Hasan, Warefta; Chu, Kevin; Gullapalli, Anuradha; Dunn, Stuart S.; Enlow, Elizabeth M.; Luft, J. Christopher; Tian, Shaomin; Napier, Mary E.; Pohlhaus, Patrick D.; Rolland, Jason P.; DeSimone, Joseph M.

    2012-01-01

    Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called PRINT (Particle Replication In Nonwetting Templates). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32–46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer. PMID:22165988

  12. The inclusion into PLGA nanoparticles enables α-bisabolol to efficiently inhibit the human dendritic cell pro-inflammatory activity

    NASA Astrophysics Data System (ADS)

    Marongiu, Laura; Donini, Marta; Bovi, Michele; Perduca, Massimiliano; Vivian, Federico; Romeo, Alessandro; Mariotto, Sofia; Monaco, Hugo L.; Dusi, Stefano

    2014-08-01

    α-bisabolol, a natural sesquiterpene alcohol, has generated considerable interest for its anti-inflammatory activity. Since the mechanisms of this anti-inflammatory action remain poorly understood, we investigated whether α-bisabolol affects the release of pro-inflammatory cytokines IL-12, IL-23, IL-6, and TNFα by human dendritic cells (DCs). We found that α-bisabolol did not induce the secretion of these cytokines and did not affect their release induced upon DC challenge with lipopolysaccharide (LPS), a well-known immune cell stimulator. As α-bisabolol is scarcely ingested by the cells, we wondered whether the inclusion of α-bisabolol into nanoparticles could favor its internalization by DCs and consequently its effects on cytokine secretion. We then prepared and characterized poly(lactic-co-glycolic acid) (PLGA) nanoparticles, with a dynamic light scattering peak centered at 154 nm and a half width at half maximum of about 48 nm. These particles were unable to affect per se cytokine secretion by both resting and LPS-stimulated DCs and were internalized by human DCs as demonstrated by confocal microscopy analysis. We then loaded PLGA nanoparticles with α-bisabolol and we observed that PLGA-associated α-bisabolol did not stimulate the cytokine release by resting DCs, but decreased IL-12, IL-23, IL-6, and TNFα secretion by LPS-stimulated DCs. Our results indicate that α-bisabolol inclusion into PLGA nanoparticles represents a very promising tool for designing new anti-inflammatory, anti-pyretic and, possibly, immunosuppressive therapeutic strategies.

  13. Comparison of intracellular accumulation and cytotoxicity of free mTHPC and mTHPC-loaded PLGA nanoparticles in human colon carcinoma cells

    NASA Astrophysics Data System (ADS)

    Löw, Karin; Knobloch, Thomas; Wagner, Sylvia; Wiehe, Arno; Engel, Andrea; Langer, Klaus; von Briesen, Hagen

    2011-06-01

    The second generation photosensitizer mTHPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that mTHPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free mTHPC and mTHPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost mTHPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer mTHPC.

  14. Optimization of Stability, Encapsulation, Release, and Cross-Priming of Tumor Antigen-Containing PLGA Nanoparticles

    PubMed Central

    Prasad, Shashi; Cody, Virginia; Saucier-Sawyer, Jennifer K.; Fadel, Tarek R.; Edelson, Richard L.; Birchall, Martin A.

    2014-01-01

    Purpose In order to investigate Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP) as potential vehicles for efficient tumor antigen (TA) delivery to dendritic cells (DC), this study aimed to optimize encapsulation/release kinetics before determining immunogenicity of antigen-containing NP. Methods Various techniques were used to liberate TA from cell lines. Single (gp100) and multiple (B16-tumor lysate containing gp100) antigens were encapsulated within differing molecular weight PLGA co-polymers. Differences in morphology, encapsulation/release and biologic potency were studied. Findings were adopted to encapsulate fresh tumor lysate from patients with advanced tumors and compare stimulation of tumor infiltrating lymphocytes (TIL) against that achieved by soluble lysate. Results Four cycles of freeze-thaw + 15 s sonication resulted in antigen-rich lysates without the need for toxic detergents or protease inhibitors. The 80KDa polymer resulted in maximal release of payload and favorable production of immunostimulatory IL-2 and IFN-γ. NP-mediated antigen delivery led to increased IFN-γ and decreased immunoinhibitory IL-10 synthesis when compared to soluble lysate. Conclusions Four cycles of freeze-thaw followed by 15 s sonication is the ideal technique to obtain complex TA for encapsulation. The 80KDa polymer has the most promising combination of release kinetics and biologic potency. Encapsulated antigens are immunogenic and evoke favorable TIL-mediated anti-tumor responses. PMID:22798259

  15. Fe3O4-based PLGA nanoparticles as MR contrast agents for the detection of thrombosis

    PubMed Central

    Liu, Jia; Xu, Jie; Zhou, Jun; Zhang, Yu; Guo, Dajing; Wang, Zhigang

    2017-01-01

    Thrombotic disease is a great threat to human health, and early detection is particularly important. Magnetic resonance (MR) molecular imaging provides noninvasive imaging with the potential for early disease diagnosis. In this study, we developed Fe3O4-based poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface-modified with a cyclic Arg-Gly-Asp (cRGD) peptide as an MR contrast agent for the detection of thrombosis. The physical and chemical characteristics, biological toxicity, ability to target thrombi, and biodistribution of the NPs were studied. The Fe3O4-PLGA-cRGD NPs were constructed successfully, and hematologic and pathologic assays indicated no in vivo toxicity of the NPs. In a rat model of FeCl3-induced abdominal aorta thrombosis, the NPs readily and selectively accumulated on the surface of the thrombosis and under vascular endothelial cells ex vivo and in vivo. In the in vivo experiment, the biodistribution of the NPs suggested that the NPs might be internalized by the macrophages of the reticuloendothelial system in the liver and the spleen. The T2 signal decreased at the mural thrombus 10 min after injection and then gradually increased until 50 min. These results suggest that the NPs are suitable for in vivo molecular imaging of thrombosis under high shear stress conditions and represent a very promising MR contrast agent for sensitive and specific detection of thrombosis. PMID:28223802

  16. mZD7349 peptide-conjugated PLGA nanoparticles directed against VCAM-1 for targeted delivery of simvastatin to restore dysfunctional HUVECs.

    PubMed

    Imanparast, Fatemeh; Faramarzi, Mohammad Ali; Vatannejad, Akram; Paknejad, Maliheh; Deiham, Behnas; Kobarfard, Farzad; Amani, Amir; Doosti, Mahmood

    2017-02-02

    Endothelial dysfunction is initial and critical step of atherosclerosis. Impaired bioavailability of endothelial nitric oxide synthase (eNOS) is one of the main reasons of endothelial dysfunction. Improving bioavailability of eNOS by increasing its expression or activity using statins is an effective therapeutic strategy in restoring endothelial dysfunction. In this study, simvastatin (SIM) as a poorly water-soluble drug was loaded in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (SIM-PLGA-NPs). NPs were then conjugated with mZD7349 peptide (mZD7349-SIM-PLGA-NPs) and directed against vascular cell adhesion molecule 1 (VCAM-1). In vitro evaluation of the NPs for targeted delivery of SIM was performed on activated Human Umbilical Cord Vascular Endothelial Cells (HUVECs) by tumor necrosis factor alpha (TNF-α). Effect of mZD7349-SIM-PLGA-NPs and SIM-PLGA-NPs was compared on eNOS phosphorylation (ser-1177). Results of western blot showed SIM post-treatment increased significantly phosphor-eNOS (Ser1177) expression but no total eNOS expression. The study showed that mZD7349-SIM-PLGA-NPs have particle size, zeta potential value, polydispersity index (PDI) and encapsulation efficacy % of 233±18nm, -9.6±1.1mV, 0.59±0.066 and 69±17.3%, respectively. Also phosphor-eNOS (Ser1177) expression in activated HUVECs treated with mZD7349-SIM-PLGA-NPs was significantly (p<0.05) better than treated cells with SIM-PLGA-NPs. The results suggest that mZD7349-SIM-PLGA-NPs may be usable as an appropriate drug carrier for restoring endothelial dysfunction.

  17. Design of PLGA-functionalized quercetin nanoparticles for potential use in Alzheimer's disease.

    PubMed

    Sun, Dongdong; Li, Nuan; Zhang, Weiwei; Zhao, Zhiwei; Mou, Zhipeng; Huang, Donghui; Liu, Jie; Wang, Weiyun

    2016-12-01

    Dysfunctional interaction of amyloid-β (Aβ) with excess metal ions is proved to be related to the etiology of Alzheimer's disease (AD). Hence, disruption of these metal-peptide interactions using nanoparticles (NPs) holds considerable promise as a therapeutic strategy to combat this incurable disease. Given that quercetin is a natural product, the biocompatibility and small size essential for permeating the blood-brain barrier make it a potential therapeutic drug candidate for treating AD. Nanocarriers formulated with the US Food and Drug Administration-approved biocompatible and biodegradable polymer PLGA are being widely explored for the controlled delivery of therapeutic drugs, proteins, peptides, oligonucleotides, and genes. With this background, the present study was undertaken to investigate the effects of PLGA-functionalized quercetin (PLGA@QT) NPs on inhibited and disassembled Aβ42 fibrils and the PLGA@QT NPs have low cytotoxicity when tested on SH-SY5Y cells in vitro. As expected, the cytotoxicity studies of the PLGA@QT NPs led to a concentration-related behaviour on the SH-SY5Y human neuroblastoma cells. And, it has demonstrated that PLGA@QT NPs can inhibit the neurotoxicity of Zn(2+)-Aβ42 system and enhance the viability of neuron cells. The results from behavioral tests indicate that injection of PLGA@QT NPs into APP/PS1 mice ameliorate cognition and memory impairments. Most encouragingly, the in vivo systemic toxicity of PLGA@QT NPs examined by histological analysis in major organs did not show any signs of adverse effect to mice. Thus, the prepared quercetin based nanoscale drug delivery carrier efficiently enhanced the therapeutic index and reduced the side effects. Our findings are highly encouraging, providing substantial evidence of the safety of PLGA@QT NPs for biomedical application. We expect these findings will be relevant for other NPs for treatment of AD and have broad implications in NP-based studies and applications.

  18. Modified poly(lactic-co-glycolic acid) nanoparticles for enhanced cellular uptake and gene editing in the lung.

    PubMed

    Fields, Rachel J; Quijano, Elias; McNeer, Nicole Ali; Caputo, Christina; Bahal, Raman; Anandalingam, Kavi; Egan, Marie E; Glazer, Peter M; Saltzman, W Mark

    2015-02-18

    Surface-modified poly(lactic-co-glycolic acid) (PLGA)/poly(β-aminoester)(PBAE)nanoparticles (NPs) have shown great promise in gene delivery. In this work, the pulmonary cellular uptake of these NPs is evaluated and surface-modified PLGA/PBAE NPs are shown to achieve higher cellular association and gene editing than traditional NPs composed of PLGA or PLGA/PBAE blends alone.

  19. Surface modified PLGA nanoparticles for brain targeting of Bacoside-A.

    PubMed

    Jose, S; Sowmya, S; Cinu, T A; Aleykutty, N A; Thomas, S; Souto, E B

    2014-10-15

    The present paper focuses on the development and in vitro/in vivo characterization of nanoparticles composed of poly-(D,L)-Lactide-co-Glycolide (PLGA) loading Bacoside-A, as a new approach for the brain delivery of the neuroprotective drug for the treatment of neurodegenerative disorders (e.g. Alzheimer Disease). Bacoside-A-loaded PLGA nanoparticles were prepared via o/w emulsion solvent evaporation technique. Surface of the nanoparticles were modified by coating with polysorbate 80 to facilitate the crossing of the blood brain barrier (BBB), and the processing parameters (i.e. sonication time, the concentration of polymer (PLGA) and surfactant (polysorbate 80), and drug-polymer ratio) were optimized with the aim to achieve a high production yield. Brain targeting potential of the nanoparticles was evaluated by in vivo studies using Wistar albino rats. The nanoparticles produced by optimal formulation were within the nanosized range (70-200 nm) with relatively low polydispersity index (0.391 ± 1.2). The encapsulation efficiency of Bacoside-A in PLGA nanoparticles was 57.11 ± 7.11%, with a drug loading capacity of 20.5 ± 1.98%. SEM images showed the spherical shape of the PLGA nanoparticles, whereas their low crystallinity was demonstrated by X-ray studies, which also confirmed no chemical interactions between the drug and polymer molecules. The in vitro release of Bacoside-A from the PLGA nanoparticles followed a sustained release pattern with a maximum release of up to 83.04 ± 2.55% in 48 h. When compared to pure drug solution (2.56 ± 1.23 μg/g tissue), in vivo study demonstrated higher brain concentration of Bacoside-A (23.94 ± 1.74 μg/g tissue) suggesting a significant role of surface coated nanoparticles on brain targeting. The results indicate the potential of surface modified PLGA nanoparticles for the delivery of Bacoside-A to the brain.

  20. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer's disease.

    PubMed

    Mathew, Anila; Fukuda, Takahiro; Nagaoka, Yutaka; Hasumura, Takashi; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Venugopal, Kizhikkilot; Kumar, D Sakthi

    2012-01-01

    Alzheimer's disease is a growing concern in the modern world. As the currently available medications are not very promising, there is an increased need for the fabrication of newer drugs. Curcumin is a plant derived compound which has potential activities beneficial for the treatment of Alzheimer's disease. Anti-amyloid activity and anti-oxidant activity of curcumin is highly beneficial for the treatment of Alzheimer's disease. The insolubility of curcumin in water restricts its use to a great extend, which can be overcome by the synthesis of curcumin nanoparticles. In our work, we have successfully synthesized water-soluble PLGA coated- curcumin nanoparticles and characterized it using different techniques. As drug targeting to diseases of cerebral origin are difficult due to the stringency of blood-brain barrier, we have coupled the nanoparticle with Tet-1 peptide, which has the affinity to neurons and possess retrograde transportation properties. Our results suggest that curcumin encapsulated-PLGA nanoparticles are able to destroy amyloid aggregates, exhibit anti-oxidative property and are non-cytotoxic. The encapsulation of the curcumin in PLGA does not destroy its inherent properties and so, the PLGA-curcumin nanoparticles can be used as a drug with multiple functions in treating Alzheimer's disease proving it to be a potential therapeutic tool against this dreaded disease.

  1. 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.

  2. Enhanced Osteoblast Functions on Nanophase Titania in Poly-lactic-co-glycolic Acid (PLGA) Composites

    DTIC Science & Technology

    2005-01-01

    Poly - lactic -co-glycolic Acid (PLGA) Composites Huinan Liu’, Elliott B. Slamovich’ and Thomas J. Webster’ 2 1School of Materials Engineering, 501...collagen matrix. For this purpose, poly - lactic -co- glycolic acid (PLGA) was dissolved in chloroform and nanometer grain size titania was dispersed by...gelatin, fibrin or collagen [4-6]), synthetic bioresorbable polymers (e.g., polylactic acid , polyglycolic acid and poly - lactic -co-glycolic acid [7-9

  3. PLGA nanoparticles from nano-emulsion templating as imaging agents: Versatile technology to obtain nanoparticles loaded with fluorescent dyes.

    PubMed

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

    2016-11-01

    The interest in polymeric nanoparticles as imaging systems for biomedical applications has increased notably in the last decades. In this work, PLGA nanoparticles, prepared from nano-emulsion templating, have been used to prepare novel fluorescent imaging agents. Two model fluorescent dyes were chosen and dissolved in the oil phase of the nano-emulsions together with PLGA. Nano-emulsions were prepared by the phase inversion composition (PIC) low-energy method. Fluorescent dye-loaded nanoparticles were obtained by solvent evaporation of nano-emulsion templates. PLGA nanoparticles loaded with the fluorescent dyes showed hydrodynamic radii lower than 40nm; markedly lower than those reported in previous studies. The small nanoparticle size was attributed to the nano-emulsification strategy used. PLGA nanoparticles showed negative surface charge and enough stability to be used for biomedical imaging purposes. Encapsulation efficiencies were higher than 99%, which was also attributed to the nano-emulsification approach as well as to the low solubility of the dyes in the aqueous component. Release kinetics of both fluorescent dyes from the nanoparticle dispersions was pH-independent and sustained. These results indicate that the dyes could remain encapsulated enough time to reach any organ and that the decrease of the pH produced during cell internalization by the endocytic route would not affect their release. Therefore, it can be assumed that these nanoparticles are appropriate as systemic imaging agents. In addition, in vitro toxicity tests showed that nanoparticles are non-cytotoxic. Consequently, it can be concluded that the preparation of PLGA nanoparticles from nano-emulsion templating represents a very versatile technology that enables obtaining biocompatible, biodegradable and safe imaging agents suitable for biomedical purposes.

  4. Targeting hepatocellular carcinoma with aptamer-functionalized PLGA/PLA-PEG nanoparticles

    NASA Astrophysics Data System (ADS)

    Weigum, Shannon E.; Sutton, Melissa; Barnes, Eugenia; Miller, Sarah; Betancourt, Tania

    2014-08-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, particularly in regions where chronic Hepatitis B and C infections are common. Nanoparticle assemblies that incorporate high-affinity aptamers which specifically bind malignant hepatocellular carcinoma cells could be useful for targeted drug delivery or enhancing contrast with existing ablation therapies. The in vitro interactions of a tumor-specific aptamer, TLS11a, were characterized in a hepatoma cell line via live-cell fluorescence imaging, SDS-PAGE and Western Blotting techniques. Cell surface binding of the aptamer-AlexaFluor®546 conjugate was found to occur within 20 minutes of initial exposure, followed by internalization and localization to late endosomes or lysosomes using a pH-sensitive LysoSensor™ Green dye and confocal microscopy. Aptamer-functionalized polymer nanoparticles containing poly(lactic-co-glycolic acid) (PLGA) and poly(lactide)-b-poly(ethylene glycol) (PLA-PEG) were then prepared by nanoprecipitation and passively loaded with the chemotherapeutic agent, doxorubicin, yielding spherical nanoparticles approximately 50 nm in diameter. Targeted drug delivery and cytotoxicity was assessed using live/dead fluorescent dyes and a MTT colorimetric viability assay with elevated levels of cell death found in cultures treated with either the aptamer-coated and uncoated polymer nanoparticles. Identification and characterization of the cell surface protein epitope(s) recognized by the TLS11a aptamer are ongoing along with nanoparticle optimization, but these preliminary studies support continued investigation of this aptamer and functionalized nanoparticle conjugates for targeted labeling and drug delivery within malignant hepatocellular carcinomas.

  5. Anticancer activity of bicalutamide-loaded PLGA nanoparticles in prostate cancers

    PubMed Central

    GUO, JUN; WU, SHU-HONG; REN, WEI-GUO; WANG, XIN-LI; YANG, AI-QING

    2015-01-01

    Prostate cancer is the most commonly diagnosed non-cutaneous malignancy in men in western and most developing countries. Bicalutamide (BLT) is an antineoplastic hormonal agent primarily used in the treatment of locally advanced and metastatic prostate cancers. In the present study, the aim was to develop a nanotechnology-based delivery system to target prostate cancer cells. This involved the development of a BLT-loaded poly(D,L-lactide-co-glycolide) PLGA (PLGA-BLT) nanoparticulate system in an attempt to improve the therapeutic efficacy of BLT in prostate cancer and to mitigate its toxicity. Nanosized particles with a uniform size distribution and spherical shape were developed. PLGA-BLT showed a pronounced cytotoxic effect on LNCaP and C4-2 cancer cells. The superior cell-killing effect of the nanoparticles may be attributable to their sustained drug-release characteristics and high cellular internalization. PLGA-BLT was also found to significantly inhibit colony formation in the two cell lines. Furthermore, the caspase-3 activity of PLGA-BLT treated cancer cells was enhanced, indicating the cell apoptosis-inducing potential of PLGA-BLT. Overall, these results suggest that nanotechnology-based formulations of BLT exhibit superior anticancer activity and have enormous potential in the treatment of prostate cancers. PMID:26668633

  6. Anticancer activity of bicalutamide-loaded PLGA nanoparticles in prostate cancers.

    PubMed

    Guo, Jun; Wu, Shu-Hong; Ren, Wei-Guo; Wang, Xin-Li; Yang, Ai-Qing

    2015-12-01

    Prostate cancer is the most commonly diagnosed non-cutaneous malignancy in men in western and most developing countries. Bicalutamide (BLT) is an antineoplastic hormonal agent primarily used in the treatment of locally advanced and metastatic prostate cancers. In the present study, the aim was to develop a nanotechnology-based delivery system to target prostate cancer cells. This involved the development of a BLT-loaded poly(D,L-lactide-co-glycolide) PLGA (PLGA-BLT) nanoparticulate system in an attempt to improve the therapeutic efficacy of BLT in prostate cancer and to mitigate its toxicity. Nanosized particles with a uniform size distribution and spherical shape were developed. PLGA-BLT showed a pronounced cytotoxic effect on LNCaP and C4-2 cancer cells. The superior cell-killing effect of the nanoparticles may be attributable to their sustained drug-release characteristics and high cellular internalization. PLGA-BLT was also found to significantly inhibit colony formation in the two cell lines. Furthermore, the caspase-3 activity of PLGA-BLT treated cancer cells was enhanced, indicating the cell apoptosis-inducing potential of PLGA-BLT. Overall, these results suggest that nanotechnology-based formulations of BLT exhibit superior anticancer activity and have enormous potential in the treatment of prostate cancers.

  7. 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.

  8. Streptomycin-loaded PLGA-alginate nanoparticles: preparation, characterization, and assessment

    NASA Astrophysics Data System (ADS)

    Asadi, Asadollah

    2013-04-01

    The aim of this study was to formulate and characterize streptomycin-loaded PLGA-alginate nanoparticles for their potential therapeutic use in Salmonella subsp. enterica ATCC 14028 infections. The streptomycin nanoparticle was prepared by solvent diffusion method, and the other properties such as size, zeta potential, loading efficacy, release kinetics, and antimicrobial strength were evaluated. The survey shows that nanoparticles may serve as a carrier of streptomycin and may provide localized antibacterial activity in the treatment of Salmonellosis. Electron microscopy showed spherical particles with indentations. The average size of the nanoparticles was 90 nm. At pH 7.2, the release kinetics of streptomycin from the nanoparticles was successfully illustrated as an initial burst defined by a first order equation that after this stage, it has a drastic tendency to obtain steady state. Nevertheless, nanoparticles showed loading efficacy nearly about 70-75 %. In addition, the tendency of concentration of streptomycin released from nanoparticles to reach antibacterial activity was similar to that of free streptomycin against PLGA-alginate, but it had threefold more antimicrobial strength in comparison with free streptomycin. This work shows the potential use of streptomycin-loaded PLGA-alginate nanoparticles and its capability.

  9. Streptomycin-loaded PLGA-alginate nanoparticles: preparation, characterization, and assessment

    NASA Astrophysics Data System (ADS)

    Asadi, Asadollah

    2014-04-01

    The aim of this study was to formulate and characterize streptomycin-loaded PLGA-alginate nanoparticles for their potential therapeutic use in Salmonella subsp. enterica ATCC 14028 infections. The streptomycin nanoparticle was prepared by solvent diffusion method, and the other properties such as size, zeta potential, loading efficacy, release kinetics, and antimicrobial strength were evaluated. The survey shows that nanoparticles may serve as a carrier of streptomycin and may provide localized antibacterial activity in the treatment of Salmonellosis. Electron microscopy showed spherical particles with indentations. The average size of the nanoparticles was 90 nm. At pH 7.2, the release kinetics of streptomycin from the nanoparticles was successfully illustrated as an initial burst defined by a first order equation that after this stage, it has a drastic tendency to obtain steady state. Nevertheless, nanoparticles showed loading efficacy nearly about 70-75 %. In addition, the tendency of concentration of streptomycin released from nanoparticles to reach antibacterial activity was similar to that of free streptomycin against PLGA-alginate, but it had threefold more antimicrobial strength in comparison with free streptomycin. This work shows the potential use of streptomycin-loaded PLGA-alginate nanoparticles and its capability.

  10. Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles.

    PubMed

    Dhar, Shanta; Gu, Frank X; Langer, Robert; Farokhzad, Omid C; Lippard, Stephen J

    2008-11-11

    Cisplatin is used to treat a variety of tumors, but dose limiting toxicities or intrinsic and acquired resistance limit its application in many types of cancer including prostate. We report a unique strategy to deliver cisplatin to prostate cancer cells by constructing Pt(IV)-encapsulated prostate-specific membrane antigen (PSMA) targeted nanoparticles (NPs) of poly(D,L-lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-functionalized controlled release polymers. By using PLGA-b-PEG nanoparticles with PSMA targeting aptamers (Apt) on the surface as a vehicle for the platinum(IV) compound c,t,c-[Pt(NH(3))(2)(O(2)CCH(2)CH(2)CH(2)CH(2)CH(3))(2)Cl(2)] (1), a lethal dose of cisplatin was delivered specifically to prostate cancer cells. PSMA aptamer targeted delivery of Pt(IV) cargos to PSMA(+) LNCaP prostate cancer cells by endocytosis of the nanoparticle vehicles was demonstrated using fluorescence microscopy by colocalization of green fluorescent labeled cholesterol-encapsulated NPs and early endosome marker EEA-1. The choice of linear hexyl chains in 1 was the result of a systematic study to optimize encapsulation and controlled release from the polymer without compromising either feature. Release of cisplatin from the polymeric nanoparticles after reduction of 1 and formation of cisplatin 1,2-intrastrand d(GpG) cross-links on nuclear DNA was confirmed by using a monoclonal antibody for the adduct. A comparison between the cytotoxic activities of Pt(IV)-encapsulated PLGA-b-PEG NPs with the PSMA aptamer on the surface (Pt-NP-Apt), cisplatin, and the nontargeted Pt(IV)-encapsulated NPs (Pt-NP) against human prostate PSMA-overexpressing LNCaP and PSMA(-) PC3 cancer cells revealed significant differences. The effectiveness of PSMA targeted Pt-NP-Apt nanoparticles against the PSMA(+) LNCaP cells is approximately an order of magnitude greater than that of free cisplatin.

  11. Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography

    NASA Astrophysics Data System (ADS)

    Swy, Eric R.; Schwartz-Duval, Aaron S.; Shuboni, Dorela D.; Latourette, Matthew T.; Mallet, Christiane L.; Parys, Maciej; Cormode, David P.; Shapiro, Erik M.

    2014-10-01

    Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ~70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging.Reports of molecular and cellular imaging using

  12. Delivery of doxorubicin-loaded PLGA nanoparticles into U87 human glioblastoma cells.

    PubMed

    Malinovskaya, Julia; Melnikov, Pavel; Baklaushev, Vladimir; Gabashvili, Anna; Osipova, Nadezhda; Mantrov, Sergey; Ermolenko, Yulia; Maksimenko, Olga; Gorshkova, Marina; Balabanyan, Vadim; Kreuter, Jörg; Gelperina, Svetlana

    2017-03-27

    The paramount problem in the therapy of brain tumors is the inability of most drugs to cross the blood-brain barrier. PLGA nanoparticles overcoated with poloxamer 188 could overcome this problem and enabled a high anti-tumoral effect against the very aggressive intracranial 101.8 glioblastoma in rats that closely resembles human grade IV glioblastomas. The basis for the transport of these particles across the blood-brain barrier appears to be adsorption of blood apolipoproteins (ApoE or ApoA-I) on the nanoparticle surface caused by the poloxamer 188-coating, followed by receptor-mediated transcytosis of the nanoparticles. The objective of the present study is the elucidation of the mechanism by which the poloxamer 188-coated nanoparticles then enter the brain tumor cells. Their intracellular fate, therefore, was investigated using the U87 human glioma cell line. The main mechanism of the PLGA nanoparticle internalization by U87 cells was clathrin-mediated endocytosis. Within 1h free doxorubicin was released from late endosomes and could reach its target site, i.e. the DNA in the nuclei without degradation, whereas the PLGA nanoparticles, which were labeled with Cy5.5, still were observed in the endo-lysosomal compartment. These results demonstrate that the underlying mechanism of action in the brain cells is by diffusive doxorubicin release from the nanoparticles rather than by their intracellular degradation.

  13. Optimization, in vitro-in vivo evaluation, and short-term tolerability of novel levofloxacin-loaded PLGA nanoparticle formulation.

    PubMed

    Kumar, Gaurav; Sharma, Sadhna; Shafiq, Nusrat; Khuller, Gopal Krishan; Malhotra, Samir

    2012-06-01

    A novel poly(lactic-co-glycolic acid) (PLGA)-based nanoformulation of levofloxacin was developed for multidrug-resistant tuberculosis with the purpose of achieving sustained release in plasma. After lyophilization of levofloxacin-loaded nanoparticles, the average size, charge, and polydispersity index were 268 ± 18 nm, -10.2 ± 1.5 mV, and 0.15 ± 0.03, respectively. The maximum drug encapsulation efficiency and loading capacity were 36.9 ± 6.1% (w/w) and 7.2 ± 1.2 mg/100 mg nanopowder, respectively. Biphasic extended-release profile was produced in vitro. Scanning electron microscopy and Fourier transform infrared studies showed spherical shape of drug-loaded nanoparticles and no drug-polymer interactions were observed. After single oral administration in mice, levofloxacin-loaded PLGA nanoparticles produced sustained release of levofloxacin for 4 days in plasma against 24 h for free levofloxacin. Levofloxacin was detected in organs (lung, liver, and spleen) for up to 4-6 days in case of levofloxacin-loaded nanoparticles, whereas free levofloxacin was cleared within 24 h. This novel formulation did not show any significant adverse effects on body weight and clinical signs in mice. No treatment-related changes were found in hematological and biochemical parameters and on histopathological evaluation. These results indicate the feasibility of development of an orally efficacious safe formulation of levofloxacin with sustained-release properties.

  14. Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography.

    PubMed

    Swy, Eric R; Schwartz-Duval, Aaron S; Shuboni, Dorela D; Latourette, Matthew T; Mallet, Christiane L; Parys, Maciej; Cormode, David P; Shapiro, Erik M

    2014-11-07

    Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ∼70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging.

  15. Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography

    PubMed Central

    Swy, Eric R.; Schwartz-Duval, Aaron S.; Shuboni, Dorela D.; Latourette, Matthew T.; Mallet, Christiane L.; Parys, Maciej; Cormode, David P.; Shapiro, Erik M.

    2015-01-01

    Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ∼ 70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging. PMID:25248645

  16. Synthesis and characterization of PLGA nanoparticles containing mixture of curcuminoids for optimization of photodynamic inactivation

    NASA Astrophysics Data System (ADS)

    Suzuki, Isabella L.; Inada, Natália M.; Marangoni, Valéria S.; Corrêa, Thaila Q.; Zucolotto, Valtencir; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-03-01

    Because of excessive use of antibiotics there is a growth in the number of resistant strains. Due to this growth of multiresistant bacteria, the number of searches looking for alternatives antibacterial therapeutic has increased, and among them is the antimicrobial photodynamic therapy (aPDT) or photodynamic inactivation (PDI). The photodynamic inactivation involves the action of a photosensitizer (PS), activated by a specific wavelength, in the present of oxygen, resulting in cytotoxic effect. Natural curcumin, consists of a mixture of three curcuminoids: curcumin, demethoxycurcumin and bis-demethoxycurcumin. Curcumin has various pharmacological properties, however, has extremely low solubility in aqueous solutions, which difficult the use as therapeutic agent. The present study aims to develop polymeric PLGA nanoparticles containing curcuminoids to improve water solubility, increase bioavailability providing protection from degradation (chemistry and physics), and to verify the efficacy in photodynamic inactivation of microorganisms. The PLGA-CURC were synthesized by nanoprecipitation, resulting in two different systems, with an average size of 172 nm and 70% encapsulation efficiency for PLGA-CURC1, and 215 nm and 80% for PLGA-CURC2. Stability tests showed the polymer protected the curcuminoids against premature degradation. Microbiological tests in vitro with curcuminoids water solution and both suspension of PLGA-CURC were efficient in Gram-positive bacterium and fungus. However, the solution presented dark toxicity at high concentrations, unlike the nanoparticles. Thus, it was concluded that it was possible to let curcuminoids water soluble by encapsulation in PLGA nanoparticles, to ensure improved stability in aqueous medium (storage), and to inactivate bacteria and fungus.

  17. Orally Administered Nano-curcumin to Attenuate Morphine Tolerance: Comparison between Negatively Charged PLGA and Partially and Fully PEGylated Nanoparticles

    PubMed Central

    Shen, Hao; Hu, Xiaoyu; Szymusiak, Magdalena; Wang, Zaijie Jim; Liu, Ying

    2014-01-01

    We have formulated hydrophobic curcurmin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] into stable nanoparticle suspensions (nano-curcumin) to overcome its relatively low bioavailability, high rate of metabolism and rapid elimination and clearance from the body. Employing the curcumin nanoformulations as the platform, we discovered that curcumin has the potential to alleviate morphine tolerance. The two types of stable polymeric nanoparticles - poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) - and the hybrid of the two were generated using flash nanoprecipitation integrated with spray drying. The optimized formulations have high drug loading (>45%), small particles size with narrow distribution, and controlled surface properties. Mice behavioral studies (tail-flick and hot-plate tests) were conducted to verify the effects of nano-curcumin on attenuating morphine tolerance. Significant analgesia was observed in mice during both tail-flick and hot-plate tests using orally administrated nano-curcumin following subcutaneous injections of morphine. However, unformulated curcumin at the same dose showed no effect. Compared with PEGylated nano-curcumin, negatively charged PLGA nanoparticles showed better functionality. PMID:24195658

  18. Orally administered nanocurcumin to attenuate morphine tolerance: comparison between negatively charged PLGA and partially and fully PEGylated nanoparticles.

    PubMed

    Shen, Hao; Hu, Xiaoyu; Szymusiak, Magdalena; Wang, Zaijie Jim; Liu, Ying

    2013-12-02

    We have formulated hydrophobic curcurmin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] into stable nanoparticle suspensions (nanocurcumin) to overcome its relatively low bioavailability, high rate of metabolism, and rapid elimination and clearance from the body. Employing the curcumin nanoformulations as the platform, we discovered that curcumin has the potential to alleviate morphine tolerance. The two types of stable polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), and the hybrid of the two were generated using flash nanoprecipitation integrated with spray drying. The optimized formulations have high drug loading (>45%), small particles size with narrow distribution, and controlled surface properties. Mice behavioral studies (tail-flick and hot-plate tests) were conducted to verify the effects of nanocurcumin on attenuating morphine tolerance. Significant analgesia was observed in mice during both tail-flick and hot-plate tests using orally administered nanocurcumin following subcutaneous injections of morphine. However, unformulated curcumin at the same dose showed no effect. Compared with PEGylated nanocurcumin, negatively charged PLGA nanoparticles showed better functionality.

  19. Biotin decorated PLGA nanoparticles containing SN-38 designed for cancer therapy.

    PubMed

    Mehdizadeh, Mozhdeh; Rouhani, Hasti; Sepehri, Nima; Varshochian, Reyhaneh; Ghahremani, Mohammad Hossein; Amini, Mohsen; Gharghabi, Mehdi; Ostad, Seyed Nasser; Atyabi, Fatemeh; Baharian, Azin; Dinarvand, Rassoul

    2017-05-01

    Active targeted chemotherapy is expected to provide more specific delivery of cytotoxic drugs to the tumor cells and hence reducing the side effects on healthy tissues. Due to the over expression of biotin receptors on cancerous cells as a result of further requirement for rapid proliferations, biotin can be a good candidate as a targeting agent. In this study, biotin decorated PLGA nanoparticles (NPs) containing SN-38 were prepared and in vitro studies were evaluated for their improved anti-cancer properties. In conclusion, biotin targeted PLGA NPs containing SN-38 showed preferential anticancer properties against tumor cells with biotin receptor over expression.

  20. 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.

  1. In vivo study of ALA PLGA nanoparticles-mediated PDT for treating cutaneous squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojie; Shi, Lei; Huang, Zheng; Wang, Xiuli

    2014-09-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still a challenge. Although topical photodynamic therapy (PDT) is effective for treating in situ and superficial SCC, the effectiveness of topical ALA delivery to thick SCC can be limited by its bioavailability. Polylactic-co-glycolic acid nanopartieles (PLGA NPs) might provide a promising ALA delivery strategy. The aim of this study was to evaluate the efficacy of ALA PLGA NPs PDT for the treatment of cutaneous SCC in a mouse model. Methods: ALA loaded PLGA NPs were prepared and characterized. The therapeutic efficacy of ALA PLGA NP mediated PDT in treating UV-induced cutaneous SCC in the mice model were examined. Results: In vivo study showed that ALA PLGA NPs PDT were more effective than free ALA of the same concentration in treating mouse cutaneous SCC. Conclusion: ALA PLGA NPs provides a promising strategy for delivering ALA and treating cutaneous SCC.

  2. Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

    PubMed Central

    2013-01-01

    Background and the aim of the study The objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology. Method A Box-Behnken design was made considering the mass ratio of drug to polymer (D/P), the volumetric proportion of the water to oil phase (W/O) and the concentration of polyvinyl alcohol (PVA) as the independent agents. PLGA-NPs were successfully prepared and the size (nm), entrapment efficiency (EE), drug loading (DL) and cumulative release of drug from NPs post 1 and 8 hrs were assessed as the responses. Results The NPs were prepared in a spherical shape and the sizes range of 240 to 316 nm. The polydispersity index of size was lower than 0.5 and the EE (%) and DL (%) varied between 14-62% and 2-6%, respectively. The optimized formulation with a desirability factor of 0.9 was selected and characterized. This formulation demonstrated the particle size of 270 nm, EE of 55%, DL of 3.9% and cumulative drug release of 79% after 12 hrs. In vitro release studies showed a burst release at the initial stage followed by a sustained release of sildenafil from NPs up to 12 hrs. The release kinetic of the optimized formulation was fitted to Higuchi model. Conclusions Sildenafil citrate NPs with small particle size, lipophilic feature, high entrapment efficiency and good loading capacity is produced by this method. Characterization of optimum formulation, provided by an evaluation of experimental data, showed no significant difference between calculated and measured data. PMID:24355133

  3. Tf-PEG-PLL-PLGA nanoparticles enhanced chemosensitivity for hypoxia-responsive tumor cells

    PubMed Central

    Liu, Ping; Zhang, Haijun; Wu, Xue; Guo, Liting; Wang, Fei; Xia, Guohua; Chen, Baoan; Yin, HaiXiang; Wang, Yonglu; Li, Xueming

    2016-01-01

    Hypoxia is an inseparable component of the solid tumor as well as the bone marrow microenvironment. In this study, we investigated the effect of the novel polyethylene glycol (PEG)-poly L-lysine (PLL)-poly lactic-co-glycolic acid (PLGA) based nanoparticles (NPs) modified by transferrin (Tf) loaded with daunorubicin (DNR) (DNR-Tf-PEG-PLL-PLGA-NPs, abbreviated as DNR-Tf-NPs) on leukemia cells (K562) under hypoxia. In vitro and in vivo tests to determine the effect of the enhanced chemosensitivity were evaluated using the immunofluorescence, flow cytometry, 3,-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazoliumbromide assay, Western blot analysis, histopathological examination, and immunohistochemistry analysis. Under hypoxia, K562 cells were hypoxia-responsive with the inhibitory concentration 50% (IC50) of DNR increased, resulting in chemotherapy insensitivity. By targeting the transferrin receptor (TfR) on the surface of K562 cells, DNR-Tf-NPs led to an increased intracellular DNR level, enhancing drug sensitivity of K562 cells to DNR with a decreased IC50, even under hypoxia. We further detected the protein levels of hypoxia-inducible factor-1α (HIF-1α), Bcl-2, Bax, and caspase-3 in K562 cells. The results indicated that DNR-Tf-NPs downregulated HIF-1α and induced apoptosis to overcome hypoxia. In the xenograft model, injection of DNR-Tf-NPs significantly suppressed tumor growth, and the immunosignals of Ki67 in DNR-Tf-NPs group was significantly lower than the other groups. It was therefore concluded that DNR-Tf-NPs could be a promising candidate for enhancing drug sensitivity under hypoxia in tumor treatment. PMID:27574446

  4. Orlistat and antisense-miRNA-loaded PLGA-PEG nanoparticles for enhanced triple negative breast cancer therapy

    PubMed Central

    Bhargava-Shah, Aarohi; Foygel, Kira; Devulapally, Rammohan; Paulmurugan, Ramasamy

    2016-01-01

    Background: This study explores the use of hydrophilic poly(ethylene glycol)-conjugated poly(lactic-co-glycolic acid) nanoparticles (PLGA-PEG-NPs) as delivery system to improve the antitumor effect of antiobesity drug orlistat for triple-negative breast cancer (TNBC) therapy by improving its bioavailability. Materials & methods: PLGA-PEG-NPs were synthesized by emulsion-diffusion-evaporation method, and the experiments were conducted in vitro in MDA-MB-231 and SKBr3 TNBC and normal breast fibroblast cells. Results: Delivery of orlistat via PLGA-PEG-NPs reduced its IC50 compared with free orlistat. Combined treatment of orlistat-loaded NPs and doxorubicin or antisense-miR-21-loaded NPs significantly enhanced apoptotic effect compared with independent doxorubicin, anti-miR-21-loaded NPs, orlistat-loaded NPs or free orlistat treatments. Conclusion: We demonstrate that orlistat in combination with antisense-miR-21 or current chemotherapy holds great promise as a novel and versatile treatment agent for TNBC. PMID:26787319

  5. Investigation and optimization of formulation parameters on preparation of targeted anti-CD205 tailored PLGA nanoparticles

    PubMed Central

    Jahan, Sheikh Tasnim; Haddadi, Azita

    2015-01-01

    The purpose of this study was to assess the effect of various formulation parameters on anti-CD205 antibody decorated poly(d, l-lactide co-glycolide) (PLGA) nanoparticles (NPs) in terms of their ability to target dendritic cells (DCs). In brief, emulsification solvent evaporation technique was adapted to design NP formulations using two different viscosity grades (low and high) of both ester and carboxylic acid terminated PLGA. Incorporation of ligand was achieved following physical adsorption or chemical conjugation processes. The physicochemical characterizations of formulations were executed to assess the effects of different solvents (chloroform and ethyl acetate), stabilizer percentage, polymer types, polymer viscosities, ligand-NP bonding types, cross-linkers, and cryoprotectants (sucrose and trehalose). Modification of any of these parameters shows significant improvement of physicochemical properties of NPs. Ethyl acetate was the solvent of choice for the formulations to ensure better emulsion formation. Infrared spectroscopy confirmed the presence of anti-CD205 antibody in the NP formulation. Finally, cytotoxicity assay confirmed the safety profile of the NPs for DCs. Thus, ligand modified structurally concealed PLGA NPs is a promising delivery tool for targeting DCs in vivo. PMID:26677326

  6. Controlled release of drug and better bioavailability using poly(lactic acid-co-glycolic acid) nanoparticles.

    PubMed

    Pandey, Sanjeev K; Patel, Dinesh K; Maurya, Akhilendra K; Thakur, Ravi; Mishra, Durga P; Vinayak, Manjula; Haldar, Chandana; Maiti, Pralay

    2016-08-01

    Tamoxifen (Tmx) embedded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-Tmx) is prepared to evaluate its better DNA cleavage potential, cytotoxicity using Dalton's lymphoma ascite (DLA) cells and MDA-MB231 breast cancer cells. PLGA-Tmx nanoparticles are prepared through emulsified nanoprecipitation technique with varying dimension of 17-30nm by changing the concentrations of polymer, emulsifier and drug. Nanoparticles dimension are measured through electron and atomic force microscopy. Interactions between tamoxifen and PLGA are verified through spectroscopic and calorimetric methods. PLGA-Tmx shows excellent DNA cleavage potential as compared to pure Tmx raising better bioavailability. In vitro cytotoxicity studies indicate that PLGA-Tmx reduces DLA cells viability up to ∼38% against ∼15% in pure Tmx. Hoechst stain is used to detect apoptotic DLA cells through fluorescence imaging of nuclear fragmentation and condensation exhibiting significant increase of apoptosis (70%) in PLGA-Tmx vis-à-vis pure drug (58%). Enhanced DNA cleavage potential, nuclear fragmentation and condensation in apoptotic cells confirm greater bioavailability of PLGA-Tmx as compared to pure Tmx in terms of receptor mediated endocytosis. Hence, the sustained release kinetics of PLGA-Tmx nanoparticles shows much better anticancer efficacy through enhanced DNA cleavage potential and nuclear fragmentation and, thereby, reveal a novel vehicle for the treatment of cancer.

  7. Docetaxel-Loaded PLGA Nanoparticles Improve Efficacy in Taxane-Resistant Triple-Negative Breast Cancer.

    PubMed

    Bowerman, Charles J; Byrne, James D; Chu, Kevin S; Schorzman, Allison N; Keeler, Amanda W; Sherwood, Candice A; Perry, Jillian L; Luft, James C; Darr, David B; Deal, Allison M; Napier, Mary E; Zamboni, William C; Sharpless, Norman E; Perou, Charles M; DeSimone, Joseph M

    2017-01-11

    Novel treatment strategies, including nanomedicine, are needed for improving management of triple-negative breast cancer. Patients with triple-negative breast cancer, when considered as a group, have a worse outcome after chemotherapy than patients with breast cancers of other subtypes, a finding that reflects the intrinsically adverse prognosis associated with the disease. The aim of this study was to improve the efficacy of docetaxel by incorporation into a novel nanoparticle platform for the treatment of taxane-resistant triple-negative breast cancer. Rod-shaped nanoparticles encapsulating docetaxel were fabricated using an imprint lithography based technique referred to as Particle Replication in Nonwetting Templates (PRINT). These rod-shaped PLGA-docetaxel nanoparticles were tested in the C3(1)-T-antigen (C3Tag) genetically engineered mouse model (GEMM) of breast cancer that represents the basal-like subtype of triple-negative breast cancer and is resistant to therapeutics from the taxane family. This GEMM recapitulates the genetics of the human disease and is reflective of patient outcome and, therefore, better represents the clinical impact of new therapeutics. Pharmacokinetic analysis showed that delivery of these PLGA-docetaxel nanoparticles increased docetaxel circulation time and provided similar docetaxel exposure to tumor compared to the clinical formulation of docetaxel, Taxotere. These PLGA-docetaxel nanoparticles improved tumor growth inhibition and significantly increased median survival time. This study demonstrates the potential of nanotechnology to improve the therapeutic index of chemotherapies and rescue therapeutic efficacy to treat nonresponsive cancers.

  8. Novel preparation of PLGA/HP55 nanoparticles for oral insulin delivery

    NASA Astrophysics Data System (ADS)

    Wu, Zhi Min; Ling, Li; Zhou, Li Ying; Guo, Xin Dong; Jiang, Wei; Qian, Yu; Luo, Kathy Qian; Zhang, Li Juan

    2012-06-01

    The aim of the present study was to develop the PLGA/HP55 nanoparticles with improved hypoglycemic effect for oral insulin delivery. The insulin-loaded PLGA/HP55 nanoparticles were produced by a modified multiple emulsion solvent evaporation method. The physicochemical characteristics, in vitro release of insulin, and in vivo efficacy in diabetic rats of the nanoparticles were evaluated. The insulin encapsulation efficiency was up to 94%, and insulin was released in a pH-dependent manner under simulated gastrointestinal conditions. When administered orally (50 IU/kg) to diabetic rats, the nanoparticles can decrease rapidly the blood glucose level with a maximal effect between 1 and 8 h. The relative bioavailability compared with subcutaneous injection (5 IU/kg) in diabetic rats was 11.3% ± 1.05%. This effect may be explained by the fast release of insulin in the upper intestine, where it is better absorbed by the high gradient concentration of insulin than other regions. These results show that the PLGA/HP55 nanoparticles developed in the study might be employed as a potential method for oral insulin delivery.

  9. Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration

    PubMed Central

    Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Pabari, Ritesh; Daly, Jacqueline; Tonda-Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

    2015-01-01

    Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3–4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. Both in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds. PMID:26343649

  10. Gas-generating TPGS-PLGA microspheres loaded with nanoparticles (NIMPS) for co-delivery of minicircle DNA and anti-tumoral drugs.

    PubMed

    Gaspar, Vítor M; Moreira, André F; Costa, Elisabete C; Queiroz, João A; Sousa, Fani; Pichon, Chantal; Correia, Ilídio J

    2015-10-01

    Drug-DNA combination therapies are receiving an ever growing focus due to their potential for improving cancer treatment. However, such approaches are still limited by the lack of multipurpose delivery systems that encapsulate drugs and condense DNA simultaneously. In this study, we describe the successful formulation of gas-generating pH-responsive D-α-tocopherol PEG succinate-poly(D,L-lactic-co-glycolic acid) (TPGS-PLGA) hollow microspheres loaded with both Doxorubicin (Dox) and minicircle DNA (mcDNA) nanoparticles as a strategy to co-deliver these therapeutics. For this study mcDNA vectors were chosen due to their increased therapeutic efficiency in comparison to standard plasmid DNA. The results demonstrate that TPGS-PLGA microcarriers can encapsulate Dox and chitosan nanoparticles completely condense mcDNA. The loading of mcDNA-nanoparticles into microspheres was confirmed by 3D confocal microscopy and co-localization analysis. The resulting TPGS-PLGA-Dox-mcDNA nanoparticle-in-microsphere hybrid carriers exhibit a well-defined spherical shape and neutral surface charge. Microcarriers incubation in acidic pH produced a gas-mediated Dox release, corroborating the microcarriers stimuli-responsive character. Also, the dual-loaded TPGS-PLGA particles achieved 5.2-fold higher cellular internalization in comparison with non-pegylated microspheres. This increased intracellular concentration resulted in a higher cytotoxic effect. Successful transgene expression was obtained after nanoparticle-mcDNA co-delivery in the microspheres. Overall these findings support the concept of using nanoparticle-microsphere multipart systems to achieve efficient co-delivery of various drug-mcDNA combinations.

  11. Hyaluronic Acid/PLGA Core/Shell Fiber Matrices Loaded with EGCG Beneficial to Diabetic Wound Healing.

    PubMed

    Shin, Yong Cheol; Shin, Dong-Myeong; Lee, Eun Ji; Lee, Jong Ho; Kim, Ji Eun; Song, Sung Hwa; Hwang, Dae-Youn; Lee, Jun Jae; Kim, Bongju; Lim, Dohyung; Hyon, Suong-Hyu; Lim, Young-Jun; Han, Dong-Wook

    2016-12-01

    During the last few decades, considerable research on diabetic wound healing strategies has been performed, but complete diabetic wound healing remains an unsolved problem, which constitutes an enormous biomedical burden. Herein, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber matrices loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) are fabricated by coaxial electrospinning. HA/PLGA-E core/shell fiber matrices are composed of randomly-oriented sub-micrometer fibers and have a 3D porous network structure. EGCG is uniformly dispersed in the shell and sustainedly released from the matrices in a stepwise manner by controlled diffusion and PLGA degradation over four weeks. EGCG does not adversely affect the thermomechanical properties of HA/PLGA-E matrices. The number of human dermal fibroblasts attached on HA/PLGA-E matrices is appreciably higher than that on HA/PLGA counterparts, while their proliferation is steadily retained on HA/PLGA-E matrices. The wound healing activity of HA/PLGA-E matrices is evaluated in streptozotocin-induced diabetic rats. After two weeks of surgical treatment, the wound areas are significantly reduced by the coverage with HA/PLGA-E matrices resulting from enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or HA/PLGA. In conclusion, the HA/PLGA-E matrices can be potentially exploited to craft strategies for the acceleration of diabetic wound healing and skin regeneration.

  12. Development and physicochemical characterization of copper complexes-loaded PLGA nanoparticles.

    PubMed

    Courant, T; Roullin, V G; Cadiou, C; Delavoie, F; Molinari, M; Andry, M C; Chuburu, F

    2009-09-11

    PLGA nanoparticles were prepared via a modified W/O/W emulsion solvent diffusion process, in which all formulation components were fully biocompatible and biodegradable. Different independent processing parameters were systematically studied. Nanoparticles were characterized by DLS (particle size, polydispersity, zeta-potential) and TEM/AFM (surface morphology). An optimized formulation was used to encapsulate copper complexes of cyclen and DOTA as potential PET imaging agents. Results showed that the predominant formulation factors appeared to be the lactide-to-glycolide (L:G) ratio of PLGA, the nature of the diffusion phase, and the presence of hydroxyl ions in the first-emulsion aqueous phase. By regulating those 3 parameters, PLGA nanoparticles were prepared with very good preparation yields (>95%), a size less than 200 nm and a polydispersity index less than 0.1. TEM pictures showed nanoparticles with a narrow size distribution, a spherical shape and a smooth surface. The optimized formulation allowed to encapsulate Cu-cyclen and Cu-DOTA complexes with an encapsulation efficiency between 20% and 25%.

  13. Doxorubicin-loaded star-shaped copolymer PLGA-vitamin E TPGS nanoparticles for lung cancer therapy.

    PubMed

    Zhang, Jinxie; Tao, Wei; Chen, Yuhan; Chang, Danfeng; Wang, Teng; Zhang, Xudong; Mei, Lin; Zeng, Xiaowei; Huang, Laiqiang

    2015-04-01

    A doxorubicin-loaded mannitol-functionalized poly(lactide-co-glycolide)-b-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles (DOX-loaded M-PLGA-b-TPGS NPs) were prepared by a modified nanoprecipitation method. The NPs were characterized by the particle size, surface morphology, particle stability, in vitro drug release and cellular uptake efficiency. The NPs were near-spherical with narrow size distribution. The size of M-PLGA-b-TPGS NPs was ~110.9 nm (much smaller than ~143.7 nm of PLGA NPs) and the zeta potential was -35.8 mV (higher than -42.6 mV of PLGA NPs). The NPs exhibited a good redispersion since the particle size and surface charge hardly changed during 3-month storage period. In the release medium (phosphate buffer solution vs. fetal bovine serum), the cumulative drug release of DOX-loaded M-PLGA-b-TPGS, PLGA-b-TPGS, and PLGA NPs were 76.41 versus 83.11 %, 58.94 versus 73.44 % and 45.14 versus 53.12 %, respectively. Compared with PLGA-b-TPGS NPs and PLGA NPs, the M-PLGA-b-TPGS NPs possessed the highest cellular uptake efficiency in A549 and H1975 cells (lung cancer cells). Ultimately, both in vitro and in vivo antitumor activities were evaluated. The results showed that M-PLGA-b-TPGS NPs could achieve a significantly higher level of cytotoxicity in cancer cells and a better antitumor efficiency on xenograft BALB/c nude mice tumor model than free DOX. In conclusion, the DOX-loaded M-PLGA-b-TPGS could be used as a potential DOX-loaded nanoformulation in lung cancer chemotherapy.

  14. Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs

    PubMed Central

    Hiremath, Jagadish; Kang, Kyung-il; Xia, Ming; Elaish, Mohamed; Binjawadagi, Basavaraj; Ouyang, Kang; Dhakal, Santosh; Arcos, Jesus; Torrelles, Jordi B.; Jiang, X.; Lee, Chang Won; Renukaradhya, Gourapura J.

    2016-01-01

    Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs. PMID:27093541

  15. Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

    PubMed

    Hiremath, Jagadish; Kang, Kyung-il; Xia, Ming; Elaish, Mohamed; Binjawadagi, Basavaraj; Ouyang, Kang; Dhakal, Santosh; Arcos, Jesus; Torrelles, Jordi B; Jiang, X; Lee, Chang Won; Renukaradhya, Gourapura J

    2016-01-01

    Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

  16. Aptamer conjugated paclitaxel and magnetic fluid loaded fluorescently tagged PLGA nanoparticles for targeted cancer therapy

    NASA Astrophysics Data System (ADS)

    Aravind, Athulya; Nair, Remya; Raveendran, Sreejith; Veeranarayanan, Srivani; Nagaoka, Yutaka; Fukuda, Takahiro; Hasumura, Takahashi; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D.

    2013-10-01

    Controlled and targeted drug delivery is an essential criterion in cancer therapy to reduce the side effects caused by non-specific drug release and toxicity. Targeted chemotherapy, sustained drug release and optical imaging have been achieved using a multifunctional nanocarrier constructed from poly (D, L-lactide-co-glycolide) nanoparticles (PLGA NPs), an anticancer drug paclitaxel (PTX), a fluorescent dye Nile red (NR), magnetic fluid (MF) and aptamers (Apt, AS1411, anti-nucleolin aptamer). The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs (MF-PTX-NR-PLGA NPs) were synthesized by a single-emulsion technique/solvent evaporation method using a chemical cross linker bis (sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. Targeting aptamers were then introduced to the particles through the reaction with the cross linker to target the nucleolin receptors over expressed on the cancer cell surface. Specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently tagged PLGA NPs (Apt-MF-NR-PLGA NPs) to the target cancer cells induced by aptamers was observed using confocal microscopy. Cytotoxicity assay conducted in two cell lines (L929 and MCF-7) confirmed that targeted MCF-7 cancer cells were killed while control cells were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and uptake to the target cancer cells exhibited increased therapeutic effect of the drug. Moreover, these aptamer conjugated magnetic polymer vehicles apart from actively transporting drugs into specifically targeted tumor regions can also be used to induce hyperthermia or for facilitating magnetic guiding of particles to the tumor regions.

  17. Synthesis and characterization of a poly(lactic-co-glycolic acid) core + poly(N-isopropylacrylamide) shell nanoparticle system.

    PubMed

    Kosinski, Aaron M; Brugnano, Jamie L; Seal, Brandon L; Knight, Frances C; Panitch, Alyssa

    2012-01-01

    Poly(lactic-co-glycolic acid) (PLGA) is a popular material used to prepare nanoparticles for drug delivery. However, PLGA nanoparticles lack desirable attributes including active targeting abilities, resistance to aggregation during lyophilization, and the ability to respond to dynamic environmental stimuli. To overcome these issues, we fabricated a nanoparticle consisting of a PLGA core encapsulated within a shell of poly(N-isopropylacrylamide). Dynamic light scattering and transmission electron microscope imaging were used to characterize the nanoparticles, while an MTT assay and ELISA suggested biocompatibility in THP1 cells. Finally, a collagen type II binding assay showed successful modification of these nanoparticles with an active targeting moiety.

  18. Genistein-loaded nanoparticles of star-shaped diblock copolymer mannitol-core PLGA-TPGS for the treatment of liver cancer.

    PubMed

    Wu, Binquan; Liang, Yong; Tan, Yi; Xie, Chunmei; Shen, Jin; Zhang, Mei; Liu, Xinkuang; Yang, Lixin; Zhang, Fujian; Liu, Liang; Cai, Shuyu; Huai, De; Zheng, Donghui; Zhang, Rongbo; Zhang, Chao; Chen, Ke; Tang, Xiaolong; Sui, Xuemei

    2016-02-01

    The purpose of this research is to develop nanoparticles (NPs) of star-shaped copolymer mannitol-functionalized PLGA-TPGS for Genistein delivery for liver cancer treatment, and evaluate their therapeutic effects in liver cancer cell line and hepatoma-tumor-bearing nude mice in comparison with the linear PLGA nanoparticles and PLGA-TPGS nanoparticles. The Genistein-loaded M-PLGA-TPGS nanoparticles (MPTN), prepared by a modified nanoprecipitation method, were observed by FESEM and TEM to be near-spherical shape with narrow size distribution. The nanoparticles were further characterized in terms of their size, size distribution, surface charge, drug-loading content, encapsulation efficiency and in vitro drug release profiles. The data showed that the M-PLGA-TPGS nanoparticles were found to be stable, showing almost no change in particle size and surface charge during 3-month storage of their aqueous solution. In vitro Genistein release from the nanoparticles exhibited biphasic pattern with burst release at the initial 4days and sustained release afterwards. The cellular uptake efficiency of fluorescent M-PLGA-TPGS nanoparticles was 1.25-, 1.22-, and 1.29-fold higher than that of the PLGA-TPGS nanoparticles at the nanoparticle concentrations of 100, 250, and 500μg/mL, respectively. In the MPTN group, the ratio of apoptotic cells increased with the drug dose increased, which exhibited dose-dependent effect and a significant difference compared with Genistein solution group (p<0.05). The data also showed that the Genistein-loaded M-PLGA-TPGS nanoparticles have higher antitumor efficacy than that of linear PLGA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, the star-shaped copolymer M-PLGA-TPGS could be used as a potential and promising bioactive material for nanomedicine development for liver cancer treatment.

  19. Development and characterization of surface modified PLGA nanoparticles for nasal vaccine delivery: effect of mucoadhesive coating on antigen uptake and immune adjuvant activity.

    PubMed

    Pawar, Dilip; Mangal, Sharad; Goswami, Roshan; Jaganathan, K S

    2013-11-01

    In this study, the efficacy of mucoadhesive polymers, i.e., chitosan and glycol chitosan as a mucoadhesive coating material in nasal vaccine delivery was investigated. The Hepatitis B surface Antigen (HBsAg) encapsulated PLGA, chitosan coated PLGA (C-PLGA), and Glycol chitosan coated PLGA (GC-PLGA) nanoparticles (NPs) were prepared. The formulations were characterized for particle size, shape, surface charge, and entrapment efficiency. The mucoadhesive ability of coated and non-coated NPs was determined using in vitro mucoadhesion and nasal clearance test. In addition, the systemic uptake and bio-distribution were also evaluated to understand the fate of NPs following nasal delivery. The immuno-adjuvant ability of various formulations was compared by measuring specific antibody titer in serum and secretory. The results indicated that PLGA NPs exhibit negative surface charge, whereas C-PLGA and GC-PLGA NPs exhibited positive surface charge. The GC-PLGA NPs demonstrated lower clearance and better local and systemic uptake compared to chitosan coated and uncoated PLGA NPs. In vivo immunogenicity studies indicated that GC-PLGA NPs could induce significantly higher systemic and mucosal immune response compared to PLGA and C-PLGA NPs. In conclusion, GC-PLGA NPs could be a promising carrier adjuvant for the nasal vaccine delivery for inducing a potent immune response at mucosal surface(s) and systemic circulation.

  20. Preparation and characterization of Chinese yam polysaccharide PLGA nanoparticles and their immunological activity.

    PubMed

    Luo, Li; Zheng, Sisi; Huang, Yifan; Qin, Tao; Xing, Jie; Niu, Yale; Bo, Ruonan; Liu, Zhenguang; Huang, Yee; Hu, Yuanliang; Liu, Jiaguo; Wu, Yi; Wang, Deyun

    2016-09-10

    This paper first provides that Chinese yam polysaccharide (CYP) is encapsulated by PLGA using a double emulsion solvent evaporation method and aims to screen the optimal preparation of CYP-PLGA nanoparticles (CYPP) using response surface methodology (RSM). The volume ratio of the internal water phase to the organic phase (W1:O), the volume ratio of the primary emulsion to the external water phase (PE:W2) and the concentration of Poloxamer 188 (F68) are deemed key variables for the encapsulation efficiency of CYPP. The results demonstrated that the data were accurately fitted into the RSM model. According to the RSM, the optimal scheme was a volume ratio of W1:O of 1:9, a volume ratio of PE: W2 of 1:10 and a concentration of F68 (W/V) of 0.7%. TEM and SEM images demonstrated that the nanoparticles had a spherical shape and smooth surface. The CYP and CYPP in vitro release studies demonstrated that the CYPP showed a release rate 53.41% lower than the release rate of CYP after 48h. The result of pro-proliferation and flow cytometry emerged that the CYPP were more effective compared with the free CYP and blank PLGA nanoparticles in promoting lymphocyte proliferation and triggering the transformation of T lymphocytes into Th cells.

  1. Synthesis, characterization and in vitro and in vivo investigation of C₃F₈-filled poly(lactic-co-glycolic acid) nanoparticles as an ultrasound contrast agent.

    PubMed

    Wang, Cui-Wei; Yang, Shi-Ping; Hu, He; Du, Jing; Li, Feng-Hua

    2015-03-01

    The present study aimed to prepare perfluoropropane (C3F8)-filled poly(lactic-co-glycolic acid) (PLGA) nanoparticles and investigate the feasibility of using PLGA nanoparticles as an ultrasound contrast agent. The PLGA nanoscale ultrasound contrast agent was prepared using a modified double-emulsion solvent evaporation method. Camphor in the form of a sublimable porogen was added to render the nanoparticles hollow and enable C3F8 gas introduction. Various physicochemical properties of PLGA nanoparticles, including morphology, size and dispersion, were analyzed by electron microscopy and dynamic laser scattering. In vitro ultrasound imaging of C3F8-filled PLGA nanoparticles was also investigated under various imaging conditions. Further in vivo ultrasound imaging was conducted on male rats following intratesticular injection of PLGA nanoparticles. C3F8-filled PLGA nanoparticles with a mean diameter of 152.0±58.08 nm were obtained. Electron microscopy revealed spherical-shaped nanoparticles with smooth surfaces, a capsular morphology and a large hollow within. In vitro ultrasound imaging of hollow PLGA nanoparticles indicated marked signal enhancement. Local intensity of the acoustical signal continued to increase during PLGA-nanoparticle injection into the testicle and the ability of hollow PLGA nanoparticles to enhance ultrasound imaging in vivo was demonstrated. The enhancement image of testicular tissue following injection with C3F8-filled PLGA nanoparticles was sustained for a minimum of five minutes. In conclusion, the hollow C3F8-filled PLGA nanoparticles were demonstrated to have potential for applications as a novel ultrasound contrast agent.

  2. Development of bicalutamide-loaded PLGA nanoparticles: preparation, characterization and in-vitro evaluation for the treatment of prostate cancer.

    PubMed

    Ray, Sayantan; Ghosh Ray, Suparna; Mandal, Supratim

    2016-06-21

    In this study we report the development and optimization of poly (D, L-lactide-co-glycolide) (PLGA) polymer encapsulated poorly aqueous soluble nonsteroidal antiandrogen drug bicalutamide, to develop a sustained release formulation for the treatment of prostate cancer. The bicalutamide-loaded PLGA nanoparticles were prepared by single emulsion (O/W) solvent evaporation method, and different process parameters like polymer concentration in the organic phase, surfactant concentration in aqueous phase and centrifugation speed for separation of nanoparticles were evaluated to optimize the drug-loaded nanoparticles. The optimum formulation of bicalutamide-loaded PLGA nanoparticles characterized extensively by different analytical techniques like laser light scattering to determine average particle size and size distribution, scanning electron microscopy (SEM) for surface morphology, powder X-ray diffraction (PXRD) for surface chemistry and differential scanning calorimetry (DSC) for thermogram properties. Significant decrease of crystallinity of bicalutamide confirms entrapment of the drug within the PLGA polymer matrix. Further, the drug encapsulation efficiency (EE) and in vitro drug release profile were measured by high-performance liquid chromatography and UV-spectrophotometry. In vitro drug release exhibited biphasic pattern with initial burst release followed by slow and continuous release up to 5 days. Optimum formulation of bicalutamide-loaded PLGA nanoparticles shows significant anti-tumor activity over prostate cancer cell lines (DU 145). The newly developed optimum formulation nanoparticles could be useful for sustained release delivery of bicalutamide.

  3. Influence of surface passivation of 2-Methoxyestradiol loaded PLGA nanoparticles on cellular interactions, pharmacokinetics and tumour accumulation.

    PubMed

    Pillai, Gopikrishna J; Paul-Prasanth, Bindhu; Nair, Shantikumar V; Menon, Deepthy

    2017-02-01

    In the present work, 2-Methoxyestradiol [2ME2] loaded PLGA nanoparticles [NPs] were stabilized with Casein or poly(ethylene glycol) [PEG] and evaluated for its cellular interactions, pharmacokinetics and tumour accumulation. Surface stabilized PLGA nanoparticles prepared through a modified emulsion route possessed similar size, surface charge, drug loading and release characteristics. Particle-cell interactions as well as the anti-angiogenesis activity were similar for both nanoformulations in vitro. However, in vivo pharmacokinetics and tumour accumulation of the drug were substantially improved for the PEGylated nanoformulation. Reduced protein binding was observed for PEG stabilized PLGA NPs. Thus, it was demonstrated that nanoencapsulation of 2-ME2 within PEGylated PLGA nanocarrier could improve its half-life and plasma concentration and thereby increase the tumour accumulation.

  4. PLGA-based dual targeted nanoparticles enhance miRNA transfection efficiency in hepatic carcinoma

    PubMed Central

    Cai, Chenlei; Xie, Yuexia; Wu, liangliang; Chen, Xiaojing; Liu, Hongmei; Zhou, Yan; Zou, Hanbing; Liu, Dejun; Zhao, Yanan; Kong, Xianming; Liu, Peifeng

    2017-01-01

    Hepatic carcinoma (HCC) is a lethal disease associated with high morbidity and poor prognosis. Recently years, gene therapies have offered novel modalities to improve the prognosis of HCC patients. MicroRNA-99a (miR-99a) is frequently down-regulated in HCC, where it acts as a tumor suppressor. Therefore, we constructed monomethoxy (polyethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(L-lysine)-lactobionic acid- anti-vascular endothelial growth factor antibody (mPEG-PLGA-PLL-LA/VEGFab or PEAL-LA/VEGFab) nanoparticles (NPs) with highly specific targeting properties as carriers to restore the expression of miR-99a both in vitro and in vivo, to inhibit HCC progression. In vitro, PEAL-LA/VEGFab NPs showed more efficient delivery of miR-99a to HepG2 cells than the conventional transfection reagent LipofectamineTM2000 (Lip2000). The higher delivery efficiency associated with PEAL-LA/VEGFab NPs consequently resulted in down-regulation of target genes and suppression of the proliferation, migration and invasion of HepG2 cells. In vivo, miR-99a-PEAL-LA/VEGFab NPs inhibited tumor xenograft growth in HCC-bearing mice without causing obvious systemic toxicity. Our results demonstrate that PEAL-LA/VEGFab NPs selectively and effectively deliver miR-99a to HCC cells based on the double-targeting character of these nanoparticles, thereby offering potential for translation into effective clinical therapies for HCC. PMID:28387375

  5. 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

  6. PLGA-based gene delivering nanoparticle enhance suppression effect of miRNA in HePG2 cells

    NASA Astrophysics Data System (ADS)

    Feng Liang, Gao; Zhu, Yan Liang; Sun, Bo; Hu, Fei Hu; Tian, Tian; Li, Shu Chun; Xiao, Zhong Dang

    2011-07-01

    The biggest challenge in the field of gene therapy is how to effectively deliver target genes to special cells. This study aimed to develop a new type of poly( D, L-lactide-co-glycolide) (PLGA)-based nanoparticles for gene delivery, which are capable of overcoming the disadvantages of polyethylenimine (PEI)- or cationic liposome-based gene carrier, such as the cytotoxicity induced by excess positive charge, as well as the aggregation on the cell surface. The PLGA-based nanoparticles presented in this study were synthesized by emulsion evaporation method and characterized by transmission electron microscopy, dynamic light scattering, and energy dispersive spectroscopy. The size of PLGA/PEI nanoparticles in phosphate-buffered saline (PBS) was about 60 nm at the optimal charge ratio. Without observable aggregation, the nanoparticles showed a better monodispersity. The PLGA-based nanoparticles were used as vector carrier for miRNA transfection in HepG2 cells. It exhibited a higher transfection efficiency and lower cytotoxicity in HepG2 cells compared to the PEI/DNA complex. The N/P ratio (ratio of the polymer nitrogen to the DNA phosphate) 6 of the PLGA/PEI/DNA nanocomplex displays the best property among various N/P proportions, yielding similar transfection efficiency when compared to Lipofectamine/DNA lipoplexes. Moreover, nanocomplex shows better serum compatibility than commercial liposome. PLGA nanocomplexes obviously accumulate in tumor cells after transfection, which indicate that the complexes contribute to cellular uptake of pDNA and pronouncedly enhance the treatment effect of miR-26a by inducing cell cycle arrest. Therefore, these results demonstrate that PLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.

  7. Dopamine-conjugated poly(lactic-co-glycolic acid) nanoparticles for protein delivery to macrophages.

    PubMed

    Lee, Song Yi; Cho, Hyun-Jong

    2017-03-15

    Poly(lactic-co-glycolic acid)-dopamine (PLGA-D)-based nanoparticles (NPs) were developed for the delivery of protein to macrophages. PLGA-D was synthesized via amide bond formation between the amine group of D and the carboxylic acid group of PLGA. Bovine serum albumin (BSA, model protein) was encapsulated in PLGA NPs and PLGA-D NPs, which had an approximately 200nm mean diameter, <0.2 polydispersity index, and negative zeta potential value. There was no increment in the mean diameters of BSA-loaded NPs after 24h of incubation in biological fluid-simulated media (i.e., aqueous buffer and serum media). The primary, secondary, and tertiary structures of BSA released from the NPs were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism, and fluorescence spectrophotometry; the structural stability of BSA was preserved during its encapsulation in the NPs and release from the NPs. PLGA/BSA NPs and PLGA-D/BSA NPs did not induce serious cytotoxicity in RAW 264.7 cells (mouse macrophage cell line) in an established concentration range. In RAW 264.7 cells, the intracellular accumulation of PLGA-D NPs was 2-fold higher than that of PLGA NPs. All of these findings indicated that PLGA-D NPs are a promising system for delivering proteins to macrophages.

  8. Synthesis, characterization, and in vitro studies of PLGA-PEG nanoparticles for oral insulin delivery.

    PubMed

    Hosseininasab, Sara; Pashaei-Asl, Roghiyeh; Khandaghi, Amir Ahmad; Nasrabadi, Hamid Tayefi; Nejati-Koshki, Kazem; Akbarzadeh, Abolfazl; Joo, Sang Woo; Hanifehpour, Younes; Davaran, Soodabeh

    2014-09-01

    Therapeutic proteins and peptides are corresponding to a major area of research in biotechnology companies and current pharmaceutical. Because of their natural instability, the enormous majority of these drugs require parentéral administration. Oral insulin delivery would be a highly attractive alternative process of administration, though it continues to be a mysterious target due to the enzymatic digestion of insulin and low levels of absorption from the gastrointestinal region. Hydrogel polymers can be considered as potential carriers for oral insulin delivery. In particular, a pH responsive hydrogel composed of PLGA-PEG has shown the ability to protect insulin from enzymes in the gastric environment and release in small intestines. However, this material has not shown similar potential for oral protein delivery of further model drugs. To date, the unique interaction between PLGA-PEG and insulin, as a potential drug for oral delivery, is not completely understood. The focus of this research is synthetization and characterization of hydrogels PLGA-PEG insulin nanoparticles and also pH sensitivity of insulin nanoparticles was investigated.

  9. Dry powders based on PLGA nanoparticles for pulmonary delivery of antibiotics: modulation of encapsulation efficiency, release rate and lung deposition pattern by hydrophilic polymers.

    PubMed

    Ungaro, Francesca; d'Angelo, Ivana; Coletta, Ciro; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella; Perfetto, Brunella; Tufano, Maria Antonietta; Miro, Agnese; La Rotonda, Maria Immacolata; Quaglia, Fabiana

    2012-01-10

    Although few experimental studies have been handled so far to exploit the potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in the production of dry powders for antibiotic inhalation, there has been no comprehensive study on the role played by NP composition. In this work, we try to shed light on this aspect by designing and developing a pulmonary delivery system for antibiotics, such as tobramycin (Tb), based on PLGA NPs embedded in an inert microcarrier made of lactose, referred to as nano-embedded micro-particles (NEM). At nanosize level, helper hydrophilic polymers were used to impart the desired surface, bulk and release properties to PLGA NPs prepared by a modified emulsion-solvent diffusion technique. Results showed that poly(vinyl alcohol) (PVA) and chitosan (CS) are essential to optimise the size and modulate the surface properties of Tb-loaded PLGA NPs, whereas the use of alginate (Alg) allows efficient Tb entrapment within NPs and its release up to one month. Optimized formulations display good in vitro antimicrobial activity against P. aeruginosa planktonic cells. Furthermore, spray-drying of the NPs with lactose yielded NEM with peculiar but promising flow and aerosolization properties, while preserving the peculiar NP features. Nonetheless, in vivo biodistribution studies showed that PVA-modified Alg/PLGA NPs reached the deep lung, while CS-modified NPs were found in great amounts in the upper airways, lining lung epithelial surfaces. In conclusion, PLGA NP composition appears to play a crucial role in determining not only the technological features of NPs but, once processed in the form of NEM, also their in vitro/in vivo deposition pattern.

  10. Evaluation of the cytotoxic effects of PLGA coated iron oxide nanoparticles as a carrier of 5- fluorouracil and mega-voltage X-ray radiation in DU145 prostate cancer cell line.

    PubMed

    Hajikarimi, Zahra; Khoei, Samideh; Khoee, Sepideh; Mahdavi, Seied Rabi

    2014-12-01

    The purpose of this study was to investigate the uptake and cytotoxic effects of magnetic poly lactic-co-glycolic acid (PLGA)-coated iron oxide nanoparticles as a carrier of 5-fluorouracil (5-FU) and X-ray on the level of proliferation capacity of DU145 prostate carcinoma cell line in monolayer culture. Following monolayer culture, DU 145 cells were treated with different concentrations of 5-FU or 5-FU loaded nanoparticles for 24 h and 2Gy X-ray (6 Mega-voltage (MV)). The rate of nanoparticles penetration was then measured using atomic adsorption spectroscopy (AAS). The cytotoxicity effect of these nanoparticles with/ without X-ray radiation was evaluated using colony formation assay. Spectroscopy results showed that iron content and therefore the cellular uptake of 5-FU loaded nanoparticles increased with increasing nanoparticle concentrations. Further, the proliferation capacity of the cells decreased with the increase of 5-FU and 5- FU loaded nanoparticle concentrations in combination with X-ray radiation. However the extent of reduction in colony number following treatment with 5-FU-loaded nanoparticles in combination with 2Gy of megavoltage X-ray radiation was significantly more than for free 5-FU. Thus, drug-loaded nanoparticles could deliver 5-FU more efficiently into the cells. PLGA coated iron oxide nanoparticles are therefore effective drug delivery vehicles for 5-FU. PLGA coated iron oxide nanoparticles are biocompatible and this coating is an appropriate surface that can penetrate into the cells.

  11. Factorial design based preparation, optimization, characterization and in vitro drug release studies of olanzapine loaded PLGA nanoparticles

    NASA Astrophysics Data System (ADS)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-12-01

    The objective of the present work was to develop and optimize olanzapine loaded polymeric nanoparticles using a factorial design. The presented work developed and optimized olanzapine loaded polymeric nanoparticles by using a 33 factorial design. The 33 factorial design was used for studying the effect of the main preparation variables on particle size and percent drug entrapment efficiency of the nanoparticles. A modified nanoprecipitation method was used to prepare nanoparticles successfully by using the biodegradable polymer poly(lactic-co-glycolic)acid (PLGA), and they were characterized for various parameters such as particle size, shape, zeta potential, percent drug entrapment efficiency, percent process yield and in vitro drug release behavior. Examination of the interaction between the excipients used as well as investigation of the nature of the drug, the formulation and the nature of the drug in the formulations was carried out by FTIR studies. Different kinetic models were used to analyze the in vitro drug release data. The preferred formulation showed a particle size of 127.6 ± 1.9 nm, PDI of 0.239 ± 0.013, zeta potential of -29.2 mV, entrapment efficiency of 72.46 ± 3.8% and process yield of 89.65 ± 1.3%. TEM results showed that these nanoparticles were spherical in shape and follow the Korsmeyer-Peppas model with different release exponent values.

  12. Vectorization of copper complexes via biocompatible and biodegradable PLGA nanoparticles

    NASA Astrophysics Data System (ADS)

    Courant, T.; Roullin, V. G.; Cadiou, C.; Delavoie, F.; Molinari, M.; Andry, M. C.; Gafa, V.; Chuburu, F.

    2010-04-01

    A double emulsion-solvent diffusion approach with fully biocompatible materials was used to encapsulate copper complexes within biodegradable nanoparticles, for which the release kinetics profiles have highlighted their potential use for a prolonged circulating administration.

  13. Vectorization of copper complexes via biocompatible and biodegradable PLGA nanoparticles.

    PubMed

    Courant, T; Roullin, V G; Cadiou, C; Delavoie, F; Molinari, M; Andry, M C; Gafa, V; Chuburu, F

    2010-04-23

    A double emulsion-solvent diffusion approach with fully biocompatible materials was used to encapsulate copper complexes within biodegradable nanoparticles, for which the release kinetics profiles have highlighted their potential use for a prolonged circulating administration.

  14. Folic acid-Functionalized Nanoparticles for Enhanced Oral Drug Delivery

    PubMed Central

    Roger, Emilie; Kalscheuer, Stephen; Kirtane, Ameya; Guru, Bharath Raja; Grill, Alex E.; Whittum-Hudson, Judith; Panyam, Jayanth

    2012-01-01

    The oral absorption of drugs that have poor bioavailability can be enhanced by encapsulation in polymeric nanoparticles. Transcellular transport of nanoparticle-encapsulated drug, possibly through transcytosis, is likely the major mechanism through which nanoparticles improve drug absorption. We hypothesized that the cellular uptake and transport of nanoparticles can be further increased by targeting the folate receptors expressed on the intestinal epithelial cells. The objective of this research was to study the effect of folic acid functionalization on transcellular transport of nanoparticle-encapsulated paclitaxel, a chemotherapeutic with poor oral bioavailability. Surface-functionalized poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with paclitaxel were prepared by the interfacial activity assisted surface functionalization technique. Transport of paclitaxel-loaded nanoparticles was investigated using Caco-2 cell monolayers as an in vitro model. Caco-2 cells were found to express folate receptor and the drug efflux protein, p-glycoprotein, to high levels. Encapsulation of paclitaxel in PLGA nanoparticles resulted in a 5-fold increase in apparent permeability (Papp) across Caco-2 cells. Functionalization of nanoparticles with folic acid further increased the transport (8-fold higher transport compared to free paclitaxel). Confocal microscopic studies showed that folic acid-functionalized nanoparticles were internalized by the cells and that nanoparticles did not have any gross effects on tight junction integrity. In conclusion, our studies indicate that folic acid functionalized nanoparticles have the potential to enhance the oral absorption of drugs with poor oral bioavailability. PMID:22670575

  15. Formulation and In vitro Interaction of Rhodamine-B Loaded PLGA Nanoparticles with Cardiac Myocytes

    PubMed Central

    Jonderian, Antranik; Maalouf, Rita

    2016-01-01

    This study aims to characterize rhodamine B (Rh B) loaded poly(D,L-lactide-co-glycolide; PLGA) nanoparticles (NPs) and their interactions with cardiac myocytes. PLGA NPs were formulated using single emulsion solvent evaporation technique. The influence of varying parameters such as the stabilizer concentration, the sonication time, and the organic to aqueous ratio were investigated. The diameter, the dispersity, the encapsulation efficiency and the zeta potential of the optimized NPs were about 184 nm, 0.19, 40% and -21.7 mV, respectively. In vitro release showed that 29% of the Rh B was released within the first 8 h. Scanning electron microscopy measurements performed on the optimized NPs showed smooth surface and spherical shapes. No significant cytotoxic or apoptotic effects were observed on cardiac myocytes after 24 and 48 h of exposure with concentrations up to 200 μg/mL. The kinetic of the intracellular uptake was confirmed by confocal microscopy and cells took up PLGA NPs within the 1st hours. Interestingly, our data show an increase in the NPs’ uptake with time of exposure. Taken together, we demonstrate for the first time that the designed NPs can be used as potential probes for drug delivery in cardiac myocytes. PMID:27999542

  16. Down-regulation of Th2 immune responses by sublingual administration of poly (lactic-co-glycolic) acid (PLGA)-encapsulated allergen in BALB/c mice.

    PubMed

    Salari, Farhad; Varasteh, Abdol-Reza; Vahedi, Fatemeh; Hashemi, Maryam; Sankian, Mojtaba

    2015-12-01

    The goal of this study was to investigate whether poly (lactic-co-glycolic) acid (PLGA) nanoparticles could enhance sublingual immunotherapy (SLIT) efficacy. BALB/c mice sensitized to rChe a 3 were treated sublingually either with soluble rChe a 3 (100μg/dose) or PLGA-encapsulated rChe a 3 (5, 25, or 50μg/dose). SLIT with PLGA-encapsulated rChe a 3 (equivalent to 25 and 50μg rChe a 3 per dose) led to significantly increased antigen-specific IgG2a, along with no effect on allergen-specific IgE and IgG1 antibody levels. In addition, interleukin 4 (IL-4) levels in restimulated splenocytes were significantly less, while interferon-γ (IFN-γ), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β) levels, as well as Foxp3 expression, were significantly greater than in the control groups. Our findings suggest that PLGA nanoparticle-based vaccination may help rational development of sublingual immunotherapy through reduction of the needed allergen doses and also significantly enhanced systemic T regulatory (Treg) and T helper 1 (Th1) immune responses.

  17. Melatonin releasing PLGA micro/nanoparticles and their effect on osteosarcoma cells.

    PubMed

    Altındal, Damla Çetin; Gümüşderelioğlu, Menemşe

    2016-02-01

    Melatonin loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles and microparticles in the diameter of ∼200 nm and 3.5 μm, respectively, were prepared by emulsion-diffusion-evaporation method. Melatonin entrapment into the particles was significantly improved with the addition of 0.2% (w/v) melatonin into the aqueous phase and encapsulation efficiencies were found as 14 and 27% for nanoparticles and microparticles, respectively. At the end of 40 days, ∼70% of melatonin was released from both of particles, with high burst release. Both blank and melatonin loaded PLGA nanoparticles caused toxic effect on the MG-63 cells due to their uptake by the cells. However, when 0.05 mg microparticle that is carrying ∼1.7 μg melatonin was added to the cm(2) of culture, inhibitory effect of melatonin on the cells were obviously observed. The results would provide an expectation about the usage of melatonin as an adjunct to the routine chemotherapy of osteosarcoma by encapsulating it into a polymeric carrier system.

  18. Claudin 4-targeted protein incorporated into PLGA nanoparticles can mediate M cell targeted delivery

    PubMed Central

    Rajapaksa, Thejani E.; Stover-Hamer, Mary; Fernandez, Xiomara; Eckelhoefer, Holly A.; Lo, David D.

    2009-01-01

    Polymer-based microparticles are in clinical use mainly for their ability to provide controlled release of peptides and compounds, but they are also being explored for their potential to deliver vaccines and drugs as suspensions directly into mucosal sites. It is generally assumed that uptake is mediated by epithelial M cells, but this is often not directly measured. To study the potential for optimizing M cell uptake of polymer microparticles in vivo, we produced sub-micron size PLGA particles incorporating a recombinant protein. This recombinant protein was produced with or without a c-terminal peptide previously shown to have high affinity binding to Claudin 4, a protein associated with M cell endocytosis. While the PLGA nanoparticles incorporate the protein throughout the matrix, much of the protein was also displayed on the surface, allowing us to take advantage of the binding activity of the targeting peptide. Accordingly, we found that instillation of these nanoparticles into the nasal passages or stomach of mice was found to significantly enhance their uptake by upper airway and intestinal M cells. Our results suggest that a reasonably simple nanoparticle manufacture method can provide insight into developing an effective needle-free delivery system. PMID:19896996

  19. Effects of lactic acid and glycolic acid on human osteoblasts: a way to understand PLGA involvement in PLGA/calcium phosphate composite failure.

    PubMed

    Meyer, Florent; Wardale, John; Best, Serena; Cameron, Ruth; Rushton, Neil; Brooks, Roger

    2012-06-01

    The use of degradable composite materials in orthopedics remains a field of intense research due to their ability to support new bone formation and degrade in a controlled manner, broadening their use for orthopedic applications. Poly (lactide-co-glycolide) acid (PLGA), a degradable biopolymer, is now a popular material for different orthopedic applications and is proposed for use in tissue engineering scaffolds either alone or combined with bioactive ceramics. Interference screws composed of calcium phosphates and PLGA are readily available in the market. However, some reports highlight problems of screw migration or aseptic cyst formation following screw degradation. In order to understand these phenomena and to help to improve implant formulation, we have evaluated the effects of PLGA degradation products: lactic acid and glycolic acid on human osteoblasts in vitro. Cell proliferation, differentiation, and matrix mineralization, important for bone healing were studied. It was found that the toxicity of polymer degradation products under buffering conditions was limited to high concentrations. However, non-toxic concentrations led to a decrease in cell proliferation, rapid cell differentiation, and mineralization failure. Calcium, whilst stimulating cell proliferation was not able to overcome the negative effects of high concentrations of lactic and glycolic acids on osteoblasts. These effects help to explain recently reported clinical failures of calcium phosphate/PLGA composites, but further in vitro analyses are needed to mimic the dynamic situation which occurs in the body by, for example, culture of osteoblasts with materials that have been pre-degraded to different extents and thus be able to relate these findings to the degradation studies that have been performed previously.

  20. Interaction between dimethyldioctadecylammonium bromide-modified PLGA microspheres and hyaluronic acid

    NASA Astrophysics Data System (ADS)

    Mulia, Kamarza; Devi, Krisanti, Elsa

    2017-02-01

    In application of intravitreal injection, an extended drug delivery system is desired so that the frequency of injection to treat diabetic retinopathy may be reduced. Poly(lactic-co-glycolic acid) polymer (PLGA) was used to encapsulate a model drug in the form of microspheres. The zeta potential of dimethyldioctadecylammonium bromide (DDAB)-modified PLGA microspheres in water was proportional to the DDAB concentration used in the preparation step, up to +57.8 mV. The scanning electron microscope pictures and the zeta potential data (SEM) confirmed that the surface of the PLGA has been modified by the cationic surfactant and that electrostatic interaction between the positively charged microspheres and the negatively charged vitreous were present.

  1. Solanum tuberosum lectin-conjugated PLGA nanoparticles for nose-to-brain delivery: in vivo and in vitro evaluations.

    PubMed

    Chen, Jie; Zhang, Chi; Liu, Qingfeng; Shao, Xiayan; Feng, Chengcheng; Shen, Yehong; Zhang, Qizhi; Jiang, Xinguo

    2012-02-01

    Solanum tuberosum lectin (STL) conjugated poly (DL-lactic-co- glycolic acid) (PLGA) nanoparticle (STL-NP) was constructed in this paper as a novel biodegradable nose-to-brain drug delivery system. The in vitro uptake study showed markedly enhanced endocytosis of STL-NP compared to unmodified PLGA nanoparticles (NP) in Calu-3 cells and significant inhibition of uptake in the presence of inhibitor sugar (chitin hydrolysate). Following intranasal administration, coumarin-6 carried by STL-NP was rapidly absorbed into blood and brain. The AUC((0→12 h)) of coumarin-6 in blood, olfactory bulb, cerebrum and cerebellum were about 0.77-, 1.48-, 1.89- and 1.45-fold of those of NP, respectively (p < 0.05). STL-NP demonstrated 1.89-2.45 times (p < 0.01) higher brain targeting efficiency in different brain tissues than unmodified NP. Enhanced accumulation of STL-NP in the brain was also observed by near infrared fluorescence probe image following intranasal administration. The fluorescence signal of STL-NP appeared in olfactory bulb, cerebrum and brainstem early at 0.25 h. The signal in olfactory bulb decreased gradually after 2 h, while the obvious signal in brainstem, cerebrum and cerebellum lasted for more than 8 h. The STL-NP safety experiments showed mild cytotoxicity and negligible cilia irritation. These intriguing in vitro and in vivo results suggest that STL-NP might serve as a promising brain drug delivery system.

  2. Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line.

    PubMed

    Chopra, Deepti; Ray, Lipika; Dwivedi, Ashish; Tiwari, Shashi Kant; Singh, Jyoti; Singh, Krishna P; Kushwaha, Hari Narayan; Jahan, Sadaf; Pandey, Ankita; Gupta, Shailendra K; Chaturvedi, Rajnish Kumar; Pant, Aditya Bhushan; Ray, Ratan Singh; Gupta, Kailash Chand

    2016-04-01

    Curcumin (Cur) has been demonstrated to have wide pharmacological window including anti-oxidant and anti-inflammatory properties. However, phototoxicity under sunlight exposure and poor biological availability limits its applicability. We have synthesized biodegradable and non-toxic polymer-poly (lactic-co-glycolic) acid (PLGA) encapsulated formulation of curcumin (PLGA-Cur-NPs) of 150 nm size range. Photochemically free curcumin generates ROS, lipid peroxidation and induces significant UVA and UVB mediated impaired mitochondrial functions leading to apoptosis/necrosis and cell injury in two different origin cell lines viz., mouse fibroblasts-NIH-3T3 and human keratinocytes-HaCaT as compared to PLGA-Cur-NPs. Molecular docking studies suggested that intact curcumin from nanoparticles, bind with BAX in BIM SAHB site and attenuate it to undergo apoptosis while upregulating anti-apoptotic genes like BCL2. Real time studies and western blot analysis with specific phosphorylation inhibitor of ERK1 and AKT1/2/3 confirm the involvement of ERK/AKT signaling molecules to trigger the survival cascade in case of PLGA-Cur-NPs. Our finding demonstrates that low level sustained release of curcumin from PLGA-Cur-NPs could be a promising way to protect the adverse biological interactions of photo-degradation products of curcumin upon the exposure of UVA and UVB. Hence, the applicability of PLGA-Cur-NPs could be suggested as prolonged radical scavenging ingredient in curcumin containing products.

  3. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo

    NASA Astrophysics Data System (ADS)

    Sun, Dongdong; Li, Nuan; Zhang, Weiwei; Yang, Endong; Mou, Zhipeng; Zhao, Zhiwei; Liu, Haiping; Wang, Weiyun

    2016-01-01

    Nanotechnology-based approaches have tremendous potential for enhancing efficacy against infectious diseases. PLGA-based nanoparticles as drug delivery carrier have shown promising potential, owing to their sizes and related unique properties. This article aims to develop nanosized poly ( d, l-lactide-co-glycolide) PLGA nanoparticle formulation loaded with quercetin (QT). QT is an antioxidant and antibacterial compound isolated from Chinese traditional medicine with low skin permeability and extreme water insolubility. The quercetin-loaded PLGA nanoparticles (PQTs) were synthesized by emulsion-solvent evaporation method and stabilized by coating with poly (vinyl alcohol). The characteristics of PQTs were analyzed by Fourier transform infrared spectroscopy, Ultraviolet-Visible spectroscopy, scanning electron microscope, transmission electron microscopy, and atomic force microscopy, respectively. The PQTs showed a spherical shape with an average size of 100-150 nm. We compared the antibacterial effects of PQTs against Escherichia coli ( E. coli) and Micrococcus tetragenus ( M. tetragenus).The PQTs produced stronger antibacterial activity to E. coli than that to M. tetragenus through disrupting bacterial cell wall integrity. The antibacterial ratio was increased with the increasing dosages and incubation time. Next, we tested the in vivo antibacterial activity in mice. No noticeable organ damage was captured from H&E-staining organ slices, suggesting the promise of using PQTs for in vivo applications. The results of this study demonstrated the interaction between bacteria and PLGA-based nanoparticles, providing encouragement for conducting further investigations on properties and antimicrobial activity of the PQTs in clinical application.

  4. Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

    PubMed Central

    Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

    2015-01-01

    Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. PMID:26316750

  5. Co-delivery of Doxorubicin Encapsulated PLGA Nanoparticles and Bcl-xL shRNA Using Alkyl-Modified PEI into Breast Cancer Cells.

    PubMed

    Ebrahimian, Mahboubeh; Taghavi, Sahar; Mokhtarzadeh, Ahad; Ramezani, Mohammad; Hashemi, Maryam

    2017-02-24

    In recent years, much effort has been focused on an appropriate combination of chemotherapeutic drugs and nucleic acids to exploit additive or synergistic therapeutic effects and overcome many obstacles such as the reduction of side effects and drug resistance. Short hairpin RNA (shRNA) has designed to allow the production of small interfering RNA (siRNA) within the cells and offer long-lasting silencing of target genes. In this study, alkyl-modified polyethylenimine (PEI 10 kD) was used for co-delivery of doxorubicin (DOX) encapsulated into poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and Bcl-xL shRNA (one class of molecules that block apoptosis of tumor cells) into breast cancer cells. Our results demonstrated that modification of PEI with alkyl chain could enhance the induction of apoptosis in tumor cells by suppression of Bcl-xL gene using Bcl-xL shRNA more than PEI alone. On the other hand, DOX encapsulated into PLGA had more synergistic effect with shRNA in comparison with DOX alone. In conclusion, combination of PLGA-DOX NPs and alkyl-PEI/shRNA complexes may have promising applications in breast cancer therapy.

  6. Glycolic acid-catalyzed deamidation of asparagine residues in degrading PLGA matrices: a computational study.

    PubMed

    Manabe, Noriyoshi; Kirikoshi, Ryota; Takahashi, Ohgi

    2015-03-31

    Poly(lactic-co-glycolic acid) (PLGA) is a strong candidate for being a drug carrier in drug delivery systems because of its biocompatibility and biodegradability. However, in degrading PLGA matrices, the encapsulated peptide and protein drugs can undergo various degradation reactions, including deamidation at asparagine (Asn) residues to give a succinimide species, which may affect their potency and/or safety. Here, we show computationally that glycolic acid (GA) in its undissociated form, which can exist in high concentration in degrading PLGA matrices, can catalyze the succinimide formation from Asn residues by acting as a proton-transfer mediator. A two-step mechanism was studied by quantum-chemical calculations using Ace-Asn-Nme (Ace = acetyl, Nme = NHCH3) as a model compound. The first step is cyclization (intramolecular addition) to form a tetrahedral intermediate, and the second step is elimination of ammonia from the intermediate. Both steps involve an extensive bond reorganization mediated by a GA molecule, and the first step was predicted to be rate-determining. The present findings are expected to be useful in the design of more effective and safe PLGA devices.

  7. Nanoscaled buffering zone of charged (PLGA)n-b-bPEI micelles in acidic microclimate for potential protein delivery application

    PubMed Central

    Kang, Han Chang; Lee, Ji Eun; Bae, You Han

    2012-01-01

    Poly(lactide-co-glycolide) (PLGA) has most often been employed for the controlled release of protein formulations because of its safety profile with non-toxic degradation products. Nevertheless, such formulations have been plagued by a local acidic microenvironment and protein-polymer interactions, which result in chemical and physical denaturation of loaded proteins and often unfavorable release profiles. This study investigated the pH change of inner PLGA microsphere (MS) using charged (PLGA)n-b-branched polyethyleneimine (bPEI) micelles. The designed micelles can be transformed into either micelle or reverse micelle (RM) depending on the solvent and RM can form microspheres. In addition, (PLGA)n-b-bPEI can be modified into (PLGA)n-b-(carboxylated bPEI) via carboxylation of the primary amines. Cationic micelle (CM) or anionic micelle (AM) were complexed with counter-charged proteins leading to nanosized particles (approximately 100 nm). In the micelle/protein complexes, the micelles mostly maintained their proton buffering capacity, and consequently, prevented or delayed the typical decrease in pH caused by degradation of PLGA in aqueous solution. Reconstitutable micelle/protein complexes allowed for increased and fine-tuned protein loading (~20 wt% when using CM1 (CM prepared from PLGA36kDa-b-bPEI25kDa)/insulin complexes) in PLGA MS. In CM2 (CM prepared from (PLGA36kDa)2-b-bPEI25kDa)/insulin (4 of weight ratio (WR) of micelle to protein; WR4)-loaded PLGA MS, CM2 strongly prevented the micellar nanoenvironmental pH (pH 6.6 within 5 days and then approximately pH 8.5) to be acidified in PLGA MS for 9 weeks, unlike CM2-free PLGA MS. In conclusion, our findings propose that the proton buffering capacity and protein loading in PLGA MS can be tuned by controlling the complexation ratios of micelles and proteins, polymeric architectures of (PLGA)n-b-bPEI copolymers and WR of micelle/protein complexes and PLGA (or RM). PMID:22405902

  8. Spray drying of siRNA-containing PLGA nanoparticles intended for inhalation.

    PubMed

    Jensen, Ditte Marie Krohn; Cun, Dongmei; Maltesen, Morten Jonas; Frokjaer, Sven; Nielsen, Hanne Mørck; Foged, Camilla

    2010-02-25

    Local delivery of small interfering RNA (siRNA) to the lungs constitutes a promising new area in drug delivery. The present study evaluated parameters of importance for spray drying of siRNA-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) into nanocomposite microparticles intended for inhalation. The spray drying process was optimised using a statistical design of experiment and by evaluating powder characteristics upon systematic variation of the formulation parameters. Concentration, carbohydrate excipient (trehalose, lactose and mannitol) and the ratio of NP to excipient were varied to monitor the effects on moisture content, particle morphology, particle size and powder yield. The identified optimum conditions were applied for spray drying of siRNA-loaded nanocomposite microparticles, resulting in a product with a low water content (0.78% w/w) and an aerodynamic particle diameter considered suitable for inhalation. The use of mannitol in the formulation allowed a significantly lower moisture content than trehalose and lactose. The inclusion of 50% (w/w) or higher amounts of NPs resulted in a marked change in the surface morphology of the spray-dried particles. Importantly, the integrity and biological activity of the siRNA were preserved during the spray drying process. In conclusion, the present results show that spray drying is a suitable technique for producing nanocomposite microparticles comprising siRNA-containing PLGA NPs for potential use in inhalation therapy.

  9. Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids

    NASA Astrophysics Data System (ADS)

    Durán-Lobato, Matilde; Martín-Banderas, Lucía; Gonçalves, Lídia M. D.; Fernández-Arévalo, Mercedes; Almeida, Antonio J.

    2015-02-01

    The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13.

  10. Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro

    PubMed Central

    Sun, Ying; Duan, You Rong; Du, Lian Fang

    2016-01-01

    A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro. Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic. PMID:27835907

  11. Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

    PubMed Central

    Moon, James J.; Suh, Heikyung; Polhemus, Mark E.; Ockenhouse, Christian F.; Yadava, Anjali; Irvine, Darrell J.

    2012-01-01

    The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) “enveloped” by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites. PMID:22328935

  12. Cationic PLGA/Eudragit RL nanoparticles for increasing retention time in synovial cavity after intra-articular injection in knee joint

    PubMed Central

    Kim, Sung Rae; Ho, Myoung Jin; Lee, Eugene; Lee, Joon Woo; Choi, Young Wook; Kang, Myung Joo

    2015-01-01

    Positively surface-charged poly(lactide-co-glycolide) (PLGA)/Eudragit RL nanoparticles (NPs) were designed to increase retention time and sustain release profile in joints after intra-articular injection, by forming micrometer-sized electrostatic aggregates with hyaluronic acid, an endogenous anionic polysaccharide found in high amounts in synovial fluid. The cationic NPs consisting of PLGA, Eudragit RL, and polyvinyl alcohol were fabricated by solvent evaporation technique. The NPs were 170.1 nm in size, with a zeta potential of 21.3 mV in phosphate-buffered saline. Hyperspectral imaging (CytoViva®) revealed the formation of the micrometer-sized filamentous aggregates upon admixing, due to electrostatic interaction between NPs and the polysaccharides. NPs loaded with a fluorescent probe (1,1′-dioctadecyl-3,3,3′,3′ tetramethylindotricarbocyanine iodide, DiR) displayed a significantly improved retention time in the knee joint, with over 50% preservation of the fluorescent signal 28 days after injection. When DiR solution was injected intra-articularly, the fluorescence levels rapidly decreased to 30% of the initial concentration within 3 days in mice. From these findings, we suggest that PLGA-based cationic NPs could be a promising tool for prolonged delivery of therapeutic agents in joints selectively. PMID:26345227

  13. Development of poly(lactic-co-glycolic) acid nanoparticles-embedded hyaluronic acid-ceramide-based nanostructure for tumor-targeted drug delivery.

    PubMed

    Park, Ju-Hwan; Lee, Jae-Young; Termsarasab, Ubonvan; Yoon, In-Soo; Ko, Seung-Hak; Shim, Jae-Seong; Cho, Hyun-Jong; Kim, Dae-Duk

    2014-10-01

    A hyaluronic acid-ceramide (HACE) nanostructure embedded with docetaxel (DCT)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) was fabricated for tumor-targeted drug delivery. NPs with a narrow size distribution and negative zeta potential were prepared by embedding DCT-loaded PLGA NPs into a HACE nanostructure (DCT/PLGA/HACE). DCT-loaded PLGA and DCT/PLGA/HACE NPs were characterized by solid-state techniques, including Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). A sustained drug release pattern from the NPs developed was observed and negligible cytotoxicity was seen in NIH3T3 cells (normal fibroblast, CD44 receptor negative) and MDA-MB-231 cells (breast cancer cells, CD44 receptor positive). PLGA/HACE NPs containing coumarin 6, used as a fluorescent dye, exhibited improved cellular uptake efficiency, based on the HA-CD44 receptor interaction, compared to plain PLGA NPs. Cyanine 5.5 (Cy5.5)-labeled PLGA/HACE NPs were injected intravenously into a MDA-MB-231 tumor xenograft mouse model and demonstrated enhanced tumor targetability, compared with Cy5.5-PLGA NPs, according to a near-infrared fluorescence (NIRF) imaging study. Considering these experimental results, the DCT/PLGA/HACE NPs developed may be useful as a tumor-targeted drug delivery system.

  14. A Comparison between the cytotoxic effects of pure curcumin and curcumin-loaded PLGA-PEG nanoparticles on the MCF-7 human breast cancer cell line.

    PubMed

    Tabatabaei Mirakabad, Fatemeh Sadat; Akbarzadeh, Abolfazl; Milani, Morteza; Zarghami, Nosratollah; Taheri-Anganeh, Mortaza; Zeighamian, Vahideh; Badrzadeh, Fariba; Rahmati-Yamchi, Mohammad

    2016-01-01

    Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women worldwide. Herbal medicines have tremendous potential as promising agents for the treatment of cancer. Curcumin is a natural polyphenol which has many anticancer effects. Because of its low aqueous solubility, low bioavailability, and quick degradation and metabolism, curcumin was released using PLGA-PEG nanoparticles. Herein, the efficiency of pure curcumin and curcumin-loaded PLGA-PEG in MCF-7 human breast cancer cell lines was studied. (1)H NMR, FT-IR and SEM demonstrated PLGA-PEG structure and curcumin loaded on nanoparticles. Subsequently, the cytotoxic effects of free curcumin and curcumin-loaded PLGA-PEG were determined via an MTT assay. Our study confirmed that curcumin-loaded PLGA-PEG has more cytotoxic effects on the MCF-7 breast cancer cell line and could be exploited as a potential source for developing novel drugs against breast cancer.

  15. PLGA-PLL-PEG-Tf-based targeted nanoparticles drug delivery system enhance antitumor efficacy via intrinsic apoptosis pathway

    PubMed Central

    Bao, Wen; Liu, Ran; Wang, Yonglu; Wang, Fei; Xia, Guohua; Zhang, Haijun; Li, Xueming; Yin, Haixiang; Chen, Baoan

    2015-01-01

    Chemotherapy offers a systemic cancer treatment; however, it is limited in clinical administration due to its serious side effects. In cancer medicine, the use of nanoparticles (NPs) drug delivery system (DDS) can sustainedly release anticancer drug at the specific site and reduce the incidence of toxicity in normal tissues. In the present study, we aimed to evaluate the benefit of a novel chemotherapeutic DDS and its underlying mechanisms. Daunorubicin (DNR) was loaded into poly (lactic-co-glycolic acid) (PLGA)-poly-l-lysine (PLL)-polyethylene glycol (PEG)-transferrin (Tf) NPs to construct DNR-PLGA-PLL-PEG-Tf-NPs (DNR-loaded NPs) as a DDS. After incubating with PLGA-PLL-PEG-Tf-NPs, DNR, and DNR-loaded NPs, the leukemia K562 cells were collected and the intracellular concentration of DNR was detected by flow cytometry, respectively. Furthermore, the effect of drugs on the growth of tumors in K562 xenografts was observed and the relevant toxicity of therapeutic drugs on organs was investigated in vivo. Meanwhile, cell apoptosis in the excised xenografts was measured by transferase-mediated dUTP nick-end labeling assay, and the expression of apoptosis-related proteins, including Bcl-2, Bax, Caspase-9, Caspase-3, and cleaved-PARP, was determined by Western blotting analysis. Results showed that DNR-loaded NPs increased intracellular concentration of DNR in K562 cells in vitro and induced a remarkable improvement in anticancer activity in the xenografts in vivo. The expression of Bcl-2 protein was downregulated and that of Bax, Caspase-9, Caspase-3, and cleaved-PARP proteins were obviously upregulated in the DNR-loaded NPs group than that in other ones. Interestingly, pathological assessment showed no apparent damage to the main organs. In summary, the results obtained from this study showed that the novel NPs DDS could improve the efficacy of DNR in the treatment of leukemia and induce apoptosis via intrinsic pathway. Thus, it can be inferred that the new drug

  16. Aeromonas hydrophila OmpW PLGA Nanoparticle Oral Vaccine Shows a Dose-Dependent Protective Immunity in Rohu (Labeo rohita).

    PubMed

    Dubey, Saurabh; Avadhani, Kiran; Mutalik, Srinivas; Sivadasan, Sangeetha Madambithara; Maiti, Biswajit; Paul, Joydeb; Girisha, Shivani Kallappa; Venugopal, Moleyur Nagarajappa; Mutoloki, Stephen; Evensen, Øystein; Karunasagar, Indrani; Munang'andu, Hetron Mweemba

    2016-06-01

    Aeromonas hydrophila is a Gram-negative bacterium that causes high mortality in different fish species and at different growth stages. Although vaccination has significantly contributed to the decline of disease outbreaks in aquaculture, the use of oral vaccines has lagged behind the injectable vaccines due to lack of proven efficacy, that being from primary immunization or by use of boost protocols. In this study, the outer membrane protein W (OmpW) of A. hydrophila was cloned, purified, and encapsulated in poly d,l-lactide-co-glycolic acid (PLGA) nanoparticles (NPs) for oral vaccination of rohu (Labeo rohita Hamilton). The physical properties of PLGA NPs encapsulating the recombinant OmpW (rOmpW) was characterized as having a diameter of 370-375 nm, encapsulation efficiency of 53% and -19.3 mV zeta potential. In vitro release of rOmpW was estimated at 34% within 48 h of incubation in phosphate-buffered saline. To evaluate the efficacy of the NP-rOmpW oral vaccine, two antigen doses were orally administered in rohu with a high antigen (HiAg) dose that had twice the amount of antigens compared to the low antigen (LoAg) dose. Antibody levels obtained after vaccination showed an antigen dose dependency in which fish from the HiAg group had higher antibody levels than those from the LoAg group. The antibody levels corresponded with post challenge survival proportions (PCSPs) and relative percent survival (RPS) in which the HiAg group had a higher PCSP and RPS than the LoAg group. Likewise, the ability to inhibit A. hydrophila growth on trypticase soy agar (TSA) by sera obtained from the HiAg group was higher than that from the LoAg group. Overall, data presented here shows that OmpW orally administered using PLGA NPs is protective against A. hydrophila infection with the level of protective immunity induced by oral vaccination being antigen dose-dependent. Future studies should seek to optimize the antigen dose and duration of oral immunization in rohu in order to

  17. Aeromonas hydrophila OmpW PLGA Nanoparticle Oral Vaccine Shows a Dose-Dependent Protective Immunity in Rohu (Labeo rohita)

    PubMed Central

    Dubey, Saurabh; Avadhani, Kiran; Mutalik, Srinivas; Sivadasan, Sangeetha Madambithara; Maiti, Biswajit; Paul, Joydeb; Girisha, Shivani Kallappa; Venugopal, Moleyur Nagarajappa; Mutoloki, Stephen; Evensen, Øystein; Karunasagar, Indrani; Munang’andu, Hetron Mweemba

    2016-01-01

    Aeromonas hydrophila is a Gram-negative bacterium that causes high mortality in different fish species and at different growth stages. Although vaccination has significantly contributed to the decline of disease outbreaks in aquaculture, the use of oral vaccines has lagged behind the injectable vaccines due to lack of proven efficacy, that being from primary immunization or by use of boost protocols. In this study, the outer membrane protein W (OmpW) of A. hydrophila was cloned, purified, and encapsulated in poly d,l-lactide-co-glycolic acid (PLGA) nanoparticles (NPs) for oral vaccination of rohu (Labeo rohita Hamilton). The physical properties of PLGA NPs encapsulating the recombinant OmpW (rOmpW) was characterized as having a diameter of 370–375 nm, encapsulation efficiency of 53% and −19.3 mV zeta potential. In vitro release of rOmpW was estimated at 34% within 48 h of incubation in phosphate-buffered saline. To evaluate the efficacy of the NP-rOmpW oral vaccine, two antigen doses were orally administered in rohu with a high antigen (HiAg) dose that had twice the amount of antigens compared to the low antigen (LoAg) dose. Antibody levels obtained after vaccination showed an antigen dose dependency in which fish from the HiAg group had higher antibody levels than those from the LoAg group. The antibody levels corresponded with post challenge survival proportions (PCSPs) and relative percent survival (RPS) in which the HiAg group had a higher PCSP and RPS than the LoAg group. Likewise, the ability to inhibit A. hydrophila growth on trypticase soy agar (TSA) by sera obtained from the HiAg group was higher than that from the LoAg group. Overall, data presented here shows that OmpW orally administered using PLGA NPs is protective against A. hydrophila infection with the level of protective immunity induced by oral vaccination being antigen dose-dependent. Future studies should seek to optimize the antigen dose and duration of oral immunization in rohu in order to

  18. In vitro characterization and in vivo analgesic and anti-allodynic activity of PLGA-bupivacaine nanoparticles

    NASA Astrophysics Data System (ADS)

    Garcia, Xavier; Escribano, Elvira; Domenech, Josep; Queralt, Josep; Freixes, Joan

    2011-05-01

    An injectable controlled release system containing local anesthetics able to provide long-lasting analgesia in nociceptive and neuropathic pain could have a marked impact in pain management. In order to address this issue, bupivacaine, a widely used local anesthetic, has been nanoencapsulated using poly(lactic-co-glycolic acid) from an oil-in-water emulsion by the solvent evaporation technique. Nanoparticles were evaluated in vitro studying their drug release mechanism by fitting different model equations, and in vivo by testing its analgesic and anti-allodynic activity in front of heat-induced nociceptive pain and sciatic nerve chronic constriction injury in rats, respectively. The particle size of the PLGA nanoparticles obtained was of 453 ± 29 nm, the encapsulation efficiency, drug loading, and burst effect at 30 min were 82.10 ± 0.001, 45.06 ± 0.001, and 4.6 ± 0.6%, respectively. A prolonged release of the drug in comparison to bupivacaine solution was seen. The mean dissolution time (MDT) obtained for nanoparticles was relatively long (9.44 ± 0.56 h) proving the sustained release process, while the dissolution efficiency (DE) (84.10 ± 1.01%) was similar to the maximum percentage of drug released. Korsmeyer-Peppas was the best model that fitted our release data. A non-Fickian mechanism was concluded to be involved in the release of bupivacaine from the nanoparticles, taking into account the value of the diffusional exponent obtained ( n = 0.95). After local infiltration in the rat, the antinociceptive and anti-allodynic activity of the nanoencapsulated bupivacaine was longer lasting than that of bupivacaine solution. An increase in the values of the area under the curve (AUC) of the antinociceptive and anti-allodynic effect versus time of 67 and 36%, respectively, was observed when the drug was encapsulated.

  19. Comparative receptor based brain delivery of tramadol-loaded poly(lactic-co-glycolic acid) nanoparticles.

    PubMed

    Lalani, Jigar; Raichandani, Yogesh; Mathur, Rashi; Lalan, Manisha; Chutani, Krishna; Mishra, Anil Kumar; Misra, Ambikanandan

    2012-12-01

    Receptor mediated endocytosis or transcytosis has been reported for drug delivery across Blood-brain barrier (BBB) and hence, the aim of the present investigations was to prepare and compare brain targeting efficiency of tramadol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface modified with transferrin (Tf) and lactoferrin (Lf). Nanoparticles of tramadol were prepared using nanoprecipitation technique and surface conjugated with Tf and Lf using epoxy linker. Prepared nanoparticles were characterized for their size, surface charge, drug entrapment, transmission electron microscopy and in vitro drug release. The surface density of Tf and Lf was estimated by protein estimation. The drug distribution in blood, brain and other tissues was studied in mice after intravenous administration. Tf and Lf anchored nanoparticles exhibit enhanced uptake with 2.38 and 3.85 folds higher targeting respectively in the brain when compared with unconjugated nanoparticles. The brain targeting observed for Lf anchored PLGA nanoparticles (Lf-TMD-PLGA-NP) was 1.62 folds that of Tf anchored PLGA nanoparticles (Tf-TMD-PLGA-NP). Hence, the study revealed Tf and specially Lf as promising ligand for enhanced brain deposition of tramadol.

  20. Development and validation of a rapid HPLC method for the quantification of GSE4 peptide in biodegradable PEI-PLGA nanoparticles.

    PubMed

    Egusquiaguirre, Susana P; Manguán-García, Cristina; Perona, Rosario; Pedraz, José Luís; Hernández, Rosa Maria; Igartua, Manuela

    2014-12-01

    In this work a high performance liquid chromatographic (HPLC) method has been developed and validated for the content determination of GSE4 peptide in PEI-PLGA nanoparticles. Chromatographic separation was performed on a C18 column, and a gradient elution with a mobile phase composed of methanol and 0.1% aqueous trifluoroacetic acid (TFA) solution, at a flow rate of 1ml/min, was used. GSE4 peptide identification was made by fluorescence detection at 290nm. The elution of methanol:TFA was initially maintained at (20:80, v/v) for one min and the gradient changed to (80:20, v/v) in 6min. This ratio was then followed by isocratic elution at (80:20, v/v) during another min and for further 3min it was linearly modified to (20:80, v/v). The developed method was validated according to the ICH guidelines, being specific, linear in the range 10-100μg/ml (R(2)=0.9996), precise, exhibiting good inter-day and intra-day precision reflected by the relative standard deviation values (less than 3.88%), accurate, with a recovery rate of 100.18±0.95%, and stable for 48h at 5°C or at RT when encapsulated in nanoparticles. The method was simple, fast, and successfully used to determine the peptide content in GSE4-loaded PEI-PLGA nanoparticles.

  1. A transferrin variant as the targeting ligand for polymeric nanoparticles incorporated in 3-D PLGA porous scaffolds.

    PubMed

    Lopes, André M; Chen, Kevin Y; Kamei, Daniel T

    2017-04-01

    We have developed doxorubicin (DOX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (DP) conjugated with polyethylene glycol (PEG) and transferrin (Tf) to form Tf-PEG-DPs (TPDPs), and incorporated these TPDPs into three-dimensional (3-D) PLGA porous scaffolds to form a controlled delivery system. To our knowledge, this represents the first use of a Tf variant (oxalate Tf) to improve the targeted delivery of drug-encapsulated nanoparticles (NPs) in PLGA scaffolds to PC3 prostate cancer cells. The PLGA scaffolds with TPDPs incorporated have been shown to release drugs for sustained delivery and provided a continuous release of DOX. The MTS assay was also performed to determine the potency of native and oxalate TPDPs, and a 3.0-fold decrease in IC50 values were observed between the native and oxalate TPDPs. The lower IC50 value for the oxalate version signifies greater potency compared to the native version, since a lower concentration of drug was required to achieve the same therapeutic effect. These results suggest that this technology has potential to become a new implantable polymeric device to improve the controlled and targeted drug delivery of Tf-conjugated NPs for cancer therapy.

  2. Effect of PEG and water-soluble chitosan coating on moxifloxacin-loaded PLGA long-circulating nanoparticles.

    PubMed

    Mustafa, Sanaul; Devi, V Kusum; Pai, Roopa S

    2017-02-01

    Moxifloxacin (MOX) is a Mycobacterium tuberculosis DNA gyrase inhibitor. Due to its intense hydrophilicity, MOX is cleared from the body within 24 h and required for repetitive doses which may then result in hepatotoxicity and acquisition of MOX resistant-TB, related with its use. To overcome the aforementioned limitations, the current study aimed to develop PLGA nanoparticles (PLGA NPs), to act as an efficient carrier for controlled delivery of MOX. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG) to MOX-PLGA NPs and adsorption of water-soluble chitosan (WSC) (cationic deacetylated chitin) to particle surface, was rose for surface modification of NPs. Surface modified NPs (MOX-PEG-WSC NPs) were prepared to provide controlled delivery and circulate in the bloodstream for an extended period of time, thus minimizing dosing frequency. In vivo pharmacokinetic and in vivo biodistribution following oral administration were investigated. NP surface charge was closed to neutral +4.76 mV and significantly affected by the WSC coating. MOX-PEG-WSC NPs presented striking prolongation in blood circulation, reduced protein binding, and long-drawn-out the blood circulation half-life with resultant reduced liver sequestration vis-à-vis MOX-PLGA NPs. The studies, therefore, indicate the successful formulation development of MOX-PEG-WSC NPs that showed sustained release behavior from nanoparticles which indicates low frequency of dosing.

  3. Antitumor effects of MsurvivinT34A-CaPi complex-embedded PLGA nanoparticles in combination with Doxil in mice

    NASA Astrophysics Data System (ADS)

    Tang, Jie; He, Jinfeng; Yang, Chengli; Mao, Yi; Hu, Tingting; Zhang, Lijing; Cao, Hua; Tong, Ai-ping; Song, Xiangrong; He, Gu; Guo, Gang; Luo, Youfu; Zhang, Xiaoning; Xie, Yongmei; Zheng, Yu

    2014-11-01

    A novel calcium phosphate-pDNA complex-embedded PLGA nanoparticles have been developed for delivering therapy genes. CaPi-MsurvivinT34A-PLGA-NPs (abbreviated as ms-CaPi-PLGA-NPs) containing the MsurvivinT34A plasmid and null-CaPi-PLGA-NPs containing the empty plasmid vector as control were prepared. The nanoparticles had mean size around 130 nm and encapsulation efficiency above 85 %. What is more, the drug loading content and zeta potential of ms-CaPi-PLGA-NPs were 0.734 ± 0.007 % and -3.75 ± 1.2 mV, respectively. ms-CaPi-PLGA-NPs combined with Doxil significantly inhibited the proliferation of 4T1 breast cancer cells with IC50 of 0.2937 ± 0.02 µg/mL, which was significantly lower than those of Doxil and null-CaPi-PLGA-NPs ( p < 0.05). Morphological analysis using Hoechst 33342 and PI staining suggested that a lot of 4T1 cells in combination therapy group of ms-CaPi-PLGA-NPs + Doxil showed typical morphological characteristic of late apoptosis and necrosis. Flow cytometry analysis with PI and the apoptosis marker Annexin V-FITC staining confirmed that apoptosis fraction given by ms-CaPi-PLGA-NPs + Doxil was greater than 80 %. Both ms-CaPi-PLGA-NPs and Doxil resulted in cell cycle arrest implying that their synergistic antitumor effect was probably related to the cell cycle regulation. Then, the antitumor effect of ms-CaPi-PLGA-NPs ( i.t.) + Doxil ( i.v.) in vivo was studied using BALB/c mice inoculated with 4T1 cells. The result showed that ms-CaPi-PLGA-NPs + Doxil suppressed the tumor growth most effectively among all the treatment groups. TUNEL assay together with immunohistochemical study on CD31 and VEGF indicated that the ideal antitumor effect of ms-CaPi-PLGA-NPs + Doxil was ascribed to induction of apoptosis (apoptotic index over 90 %) and inhibition of angiogenesis. Toxicity assessment showed that no significant toxic effects were produced after treatment of ms-CaPi-PLGA-NPs + Doxil. Above all, we may conclude that the calcium phosphate-pDNA complex

  4. ICAM-1 targeted catalase encapsulated PLGA-b-PEG nanoparticles against vascular oxidative stress.

    PubMed

    Sari, Ece; Tunc-Sarisozen, Yeliz; Mutlu, Hulya; Shahbazi, Reza; Ucar, Gulberk; Ulubayram, Kezban

    2015-01-01

    Targeted delivery of therapeutics is the favourable idea, whereas it is possible to distribute the therapeutically active drug molecule only to the site of action. For this purpose, in this study, catalase encapsulated poly(D,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles were developed and an endothelial target molecule (anti-ICAM-1) was conjugated to this carrier system in order to decrease the oxidative stress level in the target site. According to the enzymatic activity results, initial catalase activity of nanoparticles was increased from 27.39 U/mg to up to 45.66 U/mg by adding 5 mg/mL bovine serum albumin (BSA). After 4 h, initial catalase activity was preserved up to 46.98% while free catalase retained less than 4% of its activity in proteolytic environment. Furthermore, FITC labelled anti-ICAM-1 targeted catalase encapsulated nanoparticles (anti-ICAM-1/CatNPs) were rapidly taken up by cultured endothelial cells and concomitantly endothelial cells were resistant to H2O2 induced oxidative impairment.

  5. Effect of cryoprotectants on the porosity and stability of insulin-loaded PLGA nanoparticles after freeze-drying

    PubMed Central

    Fonte, Pedro; Soares, Sandra; Costa, Ana; Andrade, José Carlos; Seabra, Vítor; Reis, Salette; Sarmento, Bruno

    2012-01-01

    PLGA nanoparticles are useful to protect and deliver proteins in a localized or targeted manner, with a long-term systemic delivery pattern intended to last for a period of time, depending on polymer bioerosion and biodegradability. However, the principal concern regarding these carriers is the hydrolytic instability of polymer in aqueous suspension. Freeze-drying is a commonly used method to stabilize nanoparticles, and cryoprotectants may be also used, to even increase its physical stability. The aim of the present work was to analyze the influence of cryoprotectants on nanoparticle stability and porosity after freeze-drying, which may influence protein release and stability. It was verified that freeze-drying significantly increased the number of pores on PLGA-NP surface, being more evident when cryoprotectants are added. The presence of pores is important in a lyophilizate to facilitate its reconstitution in water, although this may have consequences to protein release and stability. The release profile of insulin encapsulated into PLGA-NP showed an initial burst in the first 2 h and a sustained release up to 48 h. After nanoparticles freeze-drying the insulin release increased about 18% in the first 2 h due to the formation of pores, maintaining a sustained release during time. After freeze-drying with cryoprotectants, the amount of insulin released was higher for trehalose and lower for sucrose, glucose, fructose and sorbitol comparatively to freeze-dried PLGA-NP with no cryoprotectant added. Besides the porosity, the ability of cryoprotectants to be adsorbed on the nanoparticles surface may also play an important role on insulin release and stability. PMID:23507897

  6. Cromolyn sodium encapsulated PLGA nanoparticles: An attempt to improve intestinal permeation.

    PubMed

    Patel, Ravi R; Chaurasia, Sundeep; Khan, Gayasuddin; Chaubey, Pramila; Kumar, Nagendra; Mishra, Brahmeshwar

    2016-02-01

    High hydrophilicity curtails the intestinal permeation of cromolyn sodium (CS) which in turn compels to compromise with its multiple biological activities. Hence, the present research was intended with an objective to develop CS encapsulated polylactide-co-glycolide (PLGA) nanoparticles (CS-PNs) for enhancing intestinal permeation. The CS-PNs were prepared by double emulsification solvent evaporation method (W1/O/W2). The "Quality by Design" approach using box-behnken experimental design was employed to enhance encapsulation of CS inside CS-PNs without compromising with particle size. The polymer concentration, surfactant concentration and organic/aqueous phase ratio significantly affected the physicochemical properties of CS-PNs. The optimized CS-PNs were subjected to various solid-state and surface characterization studies using FTIR, DSC, XRD, TEM and AFM, which pointed towards the encapsulation of CS inside the spherical shaped nanoparticles without any physical as well as chemical interactions. Ex-vivo intestinal permeation study demonstrated ∼4 fold improvements in CS permeation by forming CS-PNs as compared to pure CS. Further, in-vivo intestinal uptake study performed using confocal microscopy, after oral administration confirmed the permeation potential of CS-PNs. Thus, the findings of the studies suggest that CS-PNs could provide a superior therapeutic carrier system of CS, with enhanced intestinal permeation.

  7. CXCR4-targeted lipid-coated PLGA nanoparticles deliver sorafenib and overcome acquired drug resistance in liver cancer.

    PubMed

    Gao, Dong-Yu; Lin, Ts-Ting; Sung, Yun-Chieh; Liu, Ya Chi; Chiang, Wen-Hsuan; Chang, Chih-Chun; Liu, Jia-Yu; Chen, Yunching

    2015-10-01

    Sorafenib, a multikinase inhibitor, has been used as an anti-angiogenic agent against highly vascular hepatocellular carcinoma (HCC) - yet associated with only moderate therapeutic effect and the high incidence of HCC recurrence. We have shown intratumoral hypoxia induced by sorafenib activated C-X-C receptor type 4 (CXCR4)/stromal-derived factor 1α (SDF1α) axis, resulting in polarization toward a tumor-promoting microenvironment and resistance to anti-angiogenic therapy in HCC. Herein, we formulated sorafenib in CXCR4-targeted lipid-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with a CXCR4 antagonist, AMD3100 to systemically deliver sorafenib into HCC and sensitize HCC to sorafenib treatment. We demonstrated that CXCR4-targeted NPs efficiently delivered sorafenib into HCCs and human umbilical vein endothelial cells (HUVECs) to achieve cytotoxicity and anti-angiogenic effect in vitro and in vivo. Despite the increased expression of SDF1α upon the persistent hypoxia induced by sorafenib-loaded CXCR4-targeted NPs, AMD3100 attached to the NPs can block CXCR4/SDF1α, leading to the reduced infiltration of tumor-associated macrophages, enhanced anti-angiogenic effect, a delay in tumor progression and increased overall survival in the orthotopic HCC model compared with other control groups. In conclusion, our results highlight the clinical potential of CXCR4-targeted NPs for delivering sorafenib and overcoming acquired drug resistance in liver cancer.

  8. Delivery of phytochemicals of tropical fruit by-products using poly (DL-lactide-co-glycolide) (PLGA) nanoparticles: synthesis, characterization, and antimicrobial activity.

    PubMed

    Silva, Larissa M; Hill, Laura E; Figueiredo, Evania; Gomes, Carmen L

    2014-12-15

    Nanoencapsulation offers great potential in natural compounds delivery as it protects them from degradation, improves their aqueous solubility, and delivers active compounds to the action site. Poly (dl-lactide-co-glycolide) (PLGA) nanoparticles of acerola, guava, and passion fruit by-product extracts were synthesized using the emulsion-evaporation method. PLGA with different lactide to glycolide (50:50 and 65:35) ratios were used to determine how polymer composition affected nanoparticles properties and antimicrobial efficiency. Controlled release experiments showed an initial burst followed by a slower release rate for all encapsulated fruit by-products inside PLGA matrix. Nanoparticle properties were more dependent on by-product extract than on PLGA type. Fruit by-products and their nanoparticles were analyzed for antimicrobial activity against Listeria monocytogenes Scott A and Escherichia coli K12. All fruit by-products encapsulated in PLGA inhibited both bacteria at lower (P<0.05) concentration than corresponding unencapsulated fruit by-product. Both PLGA types improved fruit by-products delivery to pathogens and enhanced antimicrobial activity.

  9. Ultrastructural and Immunohistochemical Studies on Uptake and Distribution of FITC-Conjugated PLGA Nanoparticles Administered Intratracheally in Rats

    PubMed Central

    Hara, Kaori; Tsujimoto, Hiroyuki; Huang, C. C.; Kawashima, Yoshiaki; Ando, Rie; Kusuoka, Osamu; Tamura, Kazutoshi; Tsutsumi, Masahiro

    2012-01-01

    Polylactide-glycolide (PLGA) nanoparticles have been developed as pulmonary drug delivery carriers. To investigate their behavior, small- (d50 = 74 nm) and large-sized (d50 = 250 nm) FITC-conjugated PLGA nanoparticles were intratracheally administered to rats and were traced for 5, 30 and 60 minutes and 24 hours after administration (HAT). Immunohistochemically, a, FITC-positive reaction was observed in type-I alveolar epithelial cells (type-I AEC), endothelial cells and alveolar macrophages in the lungs from 5 minutes after treatment (MAT) to 24 HAT in both nanoparticle groups. In the kidneys, a positive reaction was observed in proximal tubular epithelial cells at 30 MAT; the reaction peaked at 60 MAT and was reduced at 24 HAT, while no positive reaction was seen in other sites. Ultrascructurally, the number of membrane-bound vesicles, which were approximately 70 nm in size and hard to distinguish from pinocytic vesicles, apparently increased in type-I AEC and endothelial cells at 5 MAT in the small-sized group, in comparison with the control group receiving physiological saline. The number of vesicles in the large-sized group was almost same as that in the control group. On the other hand, in both nanoparticle groups, lysosomes filled with nanoparticles appeared in alveolar macrophages from 30 MAT to 24 HAT. These results indicate that PLGA nanoparticles might be quickly transferred from the alveolar space to the blood vessel via type-I alveolar epithelial cells and excreted into urine, and that there is a threshold for particle size, less than approximately 70 nm in diameter, with regard to absorption through the alveolar wall. PMID:22481855

  10. Parenteral immunization of PLA/PLGA nanoparticle encapsulating outer membrane protein (Omp) from Aeromonas hydrophila: Evaluation of immunostimulatory action in Labeo rohita (rohu).

    PubMed

    Rauta, Pradipta Ranjan; Nayak, Bismita

    2015-05-01

    Advanced vaccine research approaches needs to explore on biodegradable nanoparticles (NPs) based vaccine carrier that can serve as antigen delivery systems as well as immuno-stimulatory action to induce both innate and adaptive immune response in fish. Immunogenicity of PLA and PLGA NPs encapsulating outer membrane protein (Omp) antigen of Aeromonas hydrophila were evaluated through intra-peritoneal injection in fish, Labeo rohita. Antigen loaded PLA-Omp (223.5 ± 13.19 nm) and PLGA-Omp (166.4 ± 21.23 nm) NPs were prepared using double emulsion method by efficiently encapsulating the antigen reaching the encapsulation efficiency 44 ± 4.58% and 59.33 ± 5.13% respectively. Our formulated PLA Omp and PLGA-Omp NPs were in nanometer range (<500 nm) and could be successfully endocyted in the body. Despite low antigen loading in PLA-Omp, it showed considerably slower antigen release in vitro than PLGA-Omp NPs. Other physical properties like zetapotential values and poly dispersity index (PDI) confirmed the stability as well as monodisperse nature of the formulated nanoparticles. The spherical and isolated nature of PLA-Omp and PLGA-Omp NPs were revealed by SEM analysis. Upon immunization of all antigenic formulations (PLA-Omp NP, PLGA-Omp NP, FIA-Omp, PLA NP, PLGA NP, PBS as control), significant higher bacterial agglutination titre and haemolytic activity were observed in case of PLA-Omp and PLGA-Omp immunized groups than rest groups at both 21 days and 42 days. The specific antibody response was significantly increased and persisted up to 42 days of post immunization by PLA-Omp, PLGA-Omp, FIA-Omp. PLA-Omp NPs showed better immune response (higher bacterial agglutination titre, haemolytic activity, specific antibody titre, higher percent survival upon A. hydrophila challenge) than PLGA-Omp in L. rohita confirming its better efficacy. Comparable antibody response of PLA-Omp and PLGA-Omp with FIA-Omp treated groups suggested that PLA and PLGA could be replacement for

  11. Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: in vitro and in vivo studies.

    PubMed

    Seju, U; Kumar, A; Sawant, K K

    2011-12-01

    Olanzapine (OZ) is a second-generation or atypical antipsychotic which selectively binds to central dopamine D₂ and serotonin (5-HT(2c)) receptors. It has poor bioavailability due to hepatic first-pass metabolism and low permeability into the brain due to efflux by P-glycoproteins. The present investigation aimed to prepare a nanoparticulate drug delivery system of OZ using poly(lactic-co-glycolic acid) (PLGA) for direct nose-to-brain delivery to provide brain targeting and sustained release. PLGA nanoparticles (NP) were prepared by the nanoprecipitation technique and characterized by entrapment efficiency, particle size, zeta potential, modulated temperature differential scanning calorimetry (MTDSC) and X-ray diffraction (XRD) studies. The NP were evaluated for in vitro release, ex vivo diffusion, toxicity and pharmacokinetic studies. The NP were 91.2±5.2 nm in diameter and had entrapment efficiency 68.91±2.31%. MTDSC studies indicated broadening of the drug peak and a shift in the polymer peak, possibly due to physical interaction or H-bonding between the carbonyl groups of PLGA and the NH groups of OZ, and also due to the plasticization effect of OZ on PLGA. XRD studies indicated a decrease in the crystallinity of OZ or amorphization. In vitro drug release showed a biphasic pattern with initial burst release and, later, sustained release (43.26±0.156% after 120 h), following the Fickian diffusion-based release mechanism. Ex vivo diffusion through sheep nasal mucosa showed 13.21±1.59% of drug diffusion in 210 min from NP. Histopathological study of sheep nasal mucosa showed no significant adverse effect of OZ-loaded NP. In vivo pharmacokinetic studies showed 6.35 and 10.86 times higher uptake of intranasally delivered NP than OZ solution delivered through intravenous (IV) and intranasal (IN) route, respectively. These results proved that OZ could be transported directly to the brain after IN delivery of PLGA NP, enhanced drug concentration in the brain and

  12. Antiproliferative effect of ASC-J9 delivered by PLGA nanoparticles against estrogen-dependent breast cancer cells.

    PubMed

    Verderio, Paolo; Pandolfi, Laura; Mazzucchelli, Serena; Marinozzi, Maria Rosaria; Vanna, Renzo; Gramatica, Furio; Corsi, Fabio; Colombo, Miriam; Morasso, Carlo; Prosperi, Davide

    2014-08-04

    Among polymeric nanoparticles designed for cancer therapy, PLGA nanoparticles have become one of the most popular polymeric devices for chemotherapeutic-based nanoformulations against several kinds of malignant diseases. Promising properties, including long-circulation time, enhanced tumor localization, interference with "multidrug" resistance effects, and environmental biodegradability, often result in an improvement of the drug bioavailability and effectiveness. In the present work, we have synthesized 1,7-bis(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one (ASC-J9) and developed uniform ASC-J9-loaded PLGA nanoparticles of about 120 nm, which have been prepared by a single-emulsion process. Structural and morphological features of the nanoformulation were analyzed, followed by an accurate evaluation of the in vitro drug release kinetics, which exhibited Fickian law diffusion over 10 days. The intracellular degradation of ASC-J9-bearing nanoparticles within estrogen-dependent MCF-7 breast cancer cells was correlated to a time- and dose-dependent activity of the released drug. A cellular growth inhibition associated with a specific cell cycle G2/M blocking effect caused by ASC-J9 release inside the cytosol allowed us to put forward a hypothesis on the action mechanism of this nanosystem, which led to the final cell apoptosis. Our study was accomplished using Annexin V-based cell death analysis, MTT assessment of proliferation, radical scavenging activity, and intracellular ROS evaluation. Moreover, the intracellular localization of nanoformulated ASC-J9 was confirmed by a Raman optical imaging experiment designed ad hoc. PLGA nanoparticles and ASC-J9 proved also to be safe for a healthy embryo fibroblast cell line (3T3-L1), suggesting a possible clinical translation of this potential nanochemotherapeutic to expand the inherently poor bioavailability of hydrophobic ASC-J9 that could be proposed for the treatment of malignant breast cancer.

  13. Chemical approach to solvent removal during nanoencapsulation: its application to preparation of PLGA nanoparticles with non-halogenated solvent

    NASA Astrophysics Data System (ADS)

    Lee, Youngme; Sah, Eric; Sah, Hongkee

    2015-11-01

    The objective of this study was to develop a new oil-in-water emulsion-based nanoencapsulation method for the preparation of PLGA nanoparticles using a non-halogenated solvent. PLGA (60-150 mg) was dissolved in 3 ml of methyl propionate, which was vortexed with 4 ml of a 0.5-4 % polyvinyl alcohol solution. This premix was sonicated for 2 min, added into 30 ml of the aqueous polyvinyl alcohol solution, and reacted with 3 ml of 10 N NaOH. Solvent removal was achieved by the alkaline hydrolysis of methyl propionate dissolved in an aqueous phase into water-soluble methanol and sodium propionate. It was a simple but effective technique to quickly harden nanoemulsion droplets into nanoparticles. The appearing PLGA nanoparticles were recovered by ultracentrifugation and/or dialysis, lyophilized with trehalose, and redispersed by water. This nanoencapsulation technique permitted a control of their mean diameters over 151.7 ± 3.8 to 440.2 ± 22.2 nm at mild processing conditions. When the aqueous polyvinyl alcohol concentration was set at ≥1 %, nanoparticles showed uniform distributions with polydispersity indices below 0.1. There were no significant changes in their mean diameters and size distribution patterns before and after lyophilization. When mestranol was encapsulated into nanoparticles, the drug was completely nanoencapsulated: depending on experimental conditions, their encapsulation efficiencies were determined to be 99.4 ± 7.2 to 105.8 ± 6.3 %. This simple, facile nanoencapsulation technique might have versatile applications for the preparation of polymeric nanoparticulate dosage forms.

  14. Definition of formulation design space, in vitro bioactivity and in vivo biodistribution for hydrophilic drug loaded PLGA/PEO-PPO-PEO nanoparticles using OFAT experiments.

    PubMed

    Simonoska Crcarevska, M; Geskovski, N; Calis, S; Dimchevska, S; Kuzmanovska, S; Petruševski, G; Kajdžanoska, M; Ugarkovic, S; Goracinova, K

    2013-04-11

    Modified nanoprecipitation method was used for improved incorporation of hydrophilic drug (irinotecan hydrochloride) into the PLGA/PEO-PPO-PEO blended and blended/adsorbed nanoparticles. One factor at a time (OFAT) variation experiments were conducted in order to determine key formulation factors (concentration and volume of drug solution, evaporation rate and PLGA/PEO-PPO-PEO ratio) influencing nanoparticle properties (particle size and size distribution, encapsulation efficiency, drug content, zeta potential, drug dissolution rate, as well as protein binding capacity). The insight into in vivo behavior of prepared nanoparticles and their potential for effective anticancer treatment was gained by performing biodistribution and cell culture studies as part of OFAT experiments. The mean particle size, mainly dependent upon PLGA/PEO-PPO-PEO ratio, was in the range of 112-125 nm, with narrow unimodal distribution (PDI∼0.1). Encapsulation efficiency (32-63%) was impacted by evaporation rate and PLGA/PEO-PPO-PEO ratio. Drug content (0.2-1.51%) and controlled release properties were related to the influence of all tested formulation factors. Structural information for the studied nanoparticles was obtained using DSC and FT-IR spectroscopy. Zeta potential values indicated that presence of PEO-PPO-PEO in the formulations shielded the high surface negative charge of PLGA. PEO-PPO-PEO surface coverage of PLGA/PEO-PPO-PEO blended as well as blended/adsorbed nanoparticles depended upon amount of used PEO-PPO-PEO during preparation procedure and was related to the protein resistant characteristics of nanoparticles. Results from in vivo studies evidenced prolonged blood circulation time of the prepared nanoparticles, while cell culture studies indicated higher in vitro bioefficacy compared to free drug. Performed experiments defined possible design space and justified further optimization of formulation using experimental design studies.

  15. Surface modification of PLGA nanoparticles to deliver nitric oxide to inhibit Escherichia coli growth

    NASA Astrophysics Data System (ADS)

    Reger, Nina A.; Meng, Wilson S.; Gawalt, Ellen S.

    2017-04-01

    Polymer nanoparticles consisting of poly (DL-lactic-co-glycolic acid) were surface functionalized to deliver nitric oxide. These biodegradable and biocompatible nanoparticles were modified with an S-nitrosothiol molecule, S-nitrosocysteamine, as the nitric oxide delivery molecule. S-nitrosocysteamine was covalently immobilized on the nanoparticle surface using small organic molecule linkers and carbodiimide coupling. Nanoparticle size, zeta potential, and morphology were determined using dynamic light scattering and scanning electron microscopy, respectively. Subsequent attachment of the S-nitrosothiol resulted in a nitric oxide release of 37.1 ± 1.1 nmol per milligram of nanoparticles under physiological conditions. This low concentration of nitric oxide reduced Escherichia coli culture growth by 31.8%, indicating that the nitric oxide donor was effective at releasing nitric oxide even after attachment to the nanoparticle surface. Combining the nitric oxide modified nanoparticles with tetracycline, a commonly prescribed antibiotic for E. coli infections, increased the effectiveness of the antibiotic by 87.8%, which allows for lower doses of antibiotics to be used in order to achieve the same effect. The functionalized nanoparticles were not cytotoxic to mouse fibroblasts.

  16. Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson's disease treatment.

    PubMed

    Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Liu, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

    Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson's disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box-Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.

  17. Neuroprotective effect of estradiol-loaded poly(lactic-co-glycolic acid) nanoparticles on glutamate-induced excitotoxic neuronal death.

    PubMed

    Kim, Jeong Hwan; Kim, Gyu Hyun; Jeong, Ji Heun; Lee, In Ho; Lee, Ye Ji; Lee, Nam Seob; Jeong, Young Gil; Lee, Je Hun; Yu, Kwang Sik; Lee, Shin Hye; Hong, Seul Ki; Kang, Seong Hee; Kang, Bo Sun; Kim, Do Kyung; Han, Seung Yun

    2014-11-01

    Different concentrations of estradiol (E2)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (E2-PLGA-NPs) were synthesized using the emulsion-diffusion method. Transmission electron microscopy results showed that the average particle size of E2-PLGA-NPs was 98 ± 1.9 nm when stabilized with polyvinyl alcohol and 103 ± 4.9 nm when stabilized with Tween-80. Fourier transform-infrared spectroscopy with diamond attenuated total reflectance was used to identify the presence or absence of E2 molecules in PLGA nanocapsules. Cell proliferation was assessed after treating SH-SY5Y neuroblastoma cells with 1 nM-1 μM of E2 and E2-PLGA-NPs. The neuroprotective efficacy against glutamate-induced excitotoxicity was also investigated in SH-SY5Y neuroblastoma cells. Neuroprotection was greater in E2-PLGA-NP-treated cells than in cells treated with the same concentration of E2. Furthermore, E2- and E2-PLGA-NP-treated cells expressed more p-ERK1/2 and p-CREB than cells treated with glutamate only. Moreover, the expression of p-ERK1/2 was higher than that of p-CREB. In this study, p-ERK1/2 had a greater influence on the neuroprotective effect of E2 and E2-PLGA-NPs than p-CREB.

  18. Fabrication of surfactant-free quercetin-loaded PLGA nanoparticles: evaluation of hepatoprotective efficacy by nuclear scintigraphy

    NASA Astrophysics Data System (ADS)

    Ganguly, Soumya; Gaonkar, Raghuvir H.; Sinha, Samarendu; Gupta, Amit; Chattopadhyay, Dipankar; Chattopadhyay, Sankha; Sachdeva, Satbir S.; Ganguly, Shantanu; Debnath, Mita C.

    2016-07-01

    The purpose of this study was to develop surfactant-free quercetin-loaded PLGA nanoparticles (Qr-NPs) and investigate the hepatoprotective efficacy of the product non-invasively by nuclear scintigraphy. The nanoparticles were prepared using PLGA by dialysis method and ranged in size between 50 and 250 nm with a narrow range of distribution. They were found to arrive at the fenestra of liver sinusoidal epithelium for accumulation. The sizes of nanoparticles (batch S1) were optimal to reach the target and offer enough protection of the hepatocytes degenerated by CCl4 intoxication as determined by various biochemical and histopathological tests. In vitro studies exhibited the cytotoxic effect of the formulation against HepG2 cell line. The hepatoprotective efficacy of Qr-NPs evaluated non-invasively by nuclear scintigraphic technique using 99mTc-labelled sulphur colloid revealed abnormality in liver at the area of decreased uptake in rats of CCl4-treated group, which disappeared in Qr-NP-treated group. In dynamic studies with 99mTc-mebrofenin, excretion was severely impaired in CCl4-treated group but was moderate in drug-treated group, proving the recovery of animals from damage.

  19. Click chemistry on the surface of PLGA-b-PEG polymeric nanoparticles: a novel targetable fluorescent imaging nanocarrier

    NASA Astrophysics Data System (ADS)

    Pucci, Andrea; Locatelli, Erica; Ponti, Jessica; Uboldi, Chiara; Molinari, Valerio; Comes Franchini, Mauro

    2013-08-01

    In the quest for biocompatible nanocarriers for biomedical applications, a great deal of effort is put on engineering the nanocomposites surface in order to render them specific to the particular purpose. We developed biocompatible PLGA-b-PEG-based nanoparticles carrying a double functionality (i.e., carboxylic and acetylenic) able to serve as flexible highly selective grafting centers for cancer diagnosis and treatment. As a proof of concept, the nanocarrier was successfully functionalized with a tailored fluorescent molecule by means of click chemistry and with a targeting agent specific for glioblastoma multiforme via amidic bond formation.

  20. Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles

    NASA Astrophysics Data System (ADS)

    Ganea, Gabriela M.; Fakayode, Sayo O.; Losso, Jack N.; van Nostrum, Cornelus F.; Sabliov, Cristina M.; Warner, Isiah M.

    2010-07-01

    Continuous efforts have been made in the development of potent benzoquinone-based anticancer drugs aiming for improved water solubility and reduced adverse reactions. Thymoquinone is a liposoluble benzoquinone-based phytochemical that has been shown to have remarkable antioxidant and anticancer activities. In the study reported here, thymoquinone-loaded PLGA nanoparticles were synthesized and evaluated for physico-chemical, antioxidant and anticancer properties. The nanoparticles were synthesized by an emulsion solvent evaporation method using anionic molecular micelles as emulsifiers. The system was optimized for maximum entrapment efficiency using a Box-Behnken experimental design. Optimum conditions were found for 100 mg PLGA, 15 mg TQ and 0.5% w/v poly(sodium N-undecylenyl-glycinate) (poly-SUG). In addition, other structurally related molecular micelles such as poly(sodium N-heptenyl-glycinate) (poly-SHG), poly(sodium N-undecylenyl-leucinate) (poly-SUL), and poly(sodium N-undecylenyl-valinate) (poly-SUV) were also examined as emulsifiers. All investigated molecular micelles provided excellent emulsifier properties, leading to maximum optimized TQ entrapment efficiency, and monodispersed particle sizes below 200 nm. The release of TQ from molecular micelle modified nanoparticles was investigated by dialysis and reached lower levels than the free drug. The antioxidant activity of TQ-loaded nanoparticles, indicated by IC50 (mg ml - 1 TQ for 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity), was highest for poly-SUV emulsified nanoparticles (0.030 ± 0.002 mg ml - 1) as compared to free TQ. In addition, it was observed that TQ-loaded nanoparticles emulsified with poly-SUV were more effective than free TQ against MDA-MB-231 cancer cell growth inhibition, presenting a cell viability of 16.0 ± 5.6% after 96 h.

  1. An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering.

    PubMed

    Gentile, Piergiorgio; Chiono, Valeria; Carmagnola, Irene; Hatton, Paul V

    2014-02-28

    Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function.

  2. An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering

    PubMed Central

    Gentile, Piergiorgio; Chiono, Valeria; Carmagnola, Irene; Hatton, Paul V.

    2014-01-01

    Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function. PMID:24590126

  3. Potent engineered PLGA nanoparticles by virtue of exceptionally high chemotherapeutic loadings.

    PubMed

    Enlow, Elizabeth M; Luft, J Christopher; Napier, Mary E; DeSimone, Joseph M

    2011-02-09

    Herein we report the fabrication of engineered poly(lactic acid-co-glycolic acid) nanoparticles via the PRINT (particle replication in nonwetting templates) process with high and efficient loadings of docetaxel, up to 40% (w/w) with encapsulation efficiencies >90%. The PRINT process enables independent control of particle properties leading to a higher degree of tailorability than traditional methods. Particles with 40% loading display better in vitro efficacy than particles with lower loadings and the clinical formulation of docetaxel, Taxotere.

  4. Stabilization of Human Immunoglobulin G Encapsulated within Biodegradable Poly (Cyclohexane-1, 4-diyl Acetone Dimethylene Ketal) (PCADK)/ Poly (Lactic-co-Glycolic Acid) (PLGA) Blend Microspheres.

    PubMed

    Wang, Chenhui; Yu, Changhui; Liu, Jiaxin; Sun, Fengying; Teng, Lesheng; Li, Youxin

    2015-01-01

    The aim of this study was to prepare PCADK/PLGA-blend microspheres for improving the stability of human immunoglobulin G (IgG). The short half-life of antibodies limit their development as therapeutic agents, thus PLGA microspheres were prepared to sustained release antibodies and prolong their half-life. However, the acidic intra-microsphere environment causes the loss of antibody stability and activity. In this study, the effect of PCADK or PLGA degradation products on IgG was investigated by size exclusion chromatography (SEC-HPLC), circular dichroism (CD), fluorescence spectroscopy and antigenicity detection. The degradation products of PCADK exerted a larger influence on IgG than that of PLGA. Then PCADK/PLGA microspheres were prepared by the emulsionsolvent evaporation method and systematically characterized and 20% PCADK were selected as the optimal proportion. In addition, the release profile of microspheres and the stability of the released IgG were investigated. The stability of the IgG released from the PCADK/PLGA microspheres was better than that of IgG released from the PLGA microspheres. Confocal laser scanning microscopy (CLSM) was used to determine the pH inside the microspheres. The IgG-loaded PCADK/PLGA microspheres have important advantages over the PLGA microspheres in terms of IgG stability and could be a good carrier to deliver antibodies for the treatment of disease.

  5. Developing a Highly Stable PLGA-mPEG Nanoparticle Loaded with Cisplatin for Chemotherapy of Ovarian Cancer

    PubMed Central

    Cheng, Lihua; Jin, Chengmeng; Lv, Wen; Ding, Qiuping; Han, Xu

    2011-01-01

    Background Cisplatin is a potent anticancer drug, but its clinical application has been limited due to its undesirable physicochemical characteristics and severe side effects. Better drug formulations for cisplatin are highly desired. Methodology/Principal Findings Herein, we have developed a nanoparticle formulation for cisplatin with high encapsulation efficiency and reduced toxicity by using cisplatin-crosslinked carboxymethyl cellulose (CMC) core nanoparticles made from poly(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol) copolymers (PLGA-mPEG). The nanoparticles have an average diameter of approximately 80 nm measured by transmission electron microscope (TEM). The encapsulation efficiency of cisplatin in the nanoparticles is up to 72%. Meanwhile, we have also observed a controlled release of cisplatin in a sustained manner and dose-dependent treatment efficacy of cisplatin-loaded nanoparticles against IGROV1-CP cells. Moreover, the median lethal dose (LD50) of the cisplatin-loaded nanoparticles was more than 100 mg/kg by intravenous administration, which was much higher than that of free cisplatin. Conclusion This developed cisplatin-loaded nanoparticle is a promising formulation for the delivery of cisplatin, which will be an effective therapeutic regimen of ovarian cancer without severe side effects and cumulative toxicity. PMID:21966528

  6. Herceptin conjugated PLGA-PHis-PEG pH sensitive nanoparticles for targeted and controlled drug delivery.

    PubMed

    Zhou, Zilan; Badkas, Apurva; Stevenson, Max; Lee, Joo-Youp; Leung, Yuet-Kin

    2015-06-20

    A dual functional nano-scaled drug carrier, comprising of a targeting ligand and pH sensitivity, has been made in order to increase the specificity and efficacy of the drug delivery system. The nanoparticles are made of a tri-block copolymer, poly(d,l lactide-co-glycolide) (PLGA)-b-poly(l-histidine) (PHis)-b-polyethylene glycol (PEG), via nano-precipitation. To provide the nanoparticle feature of endolysosomal escape and pH sensitivity, poly(l-histidine) was chosen as a proton sponge polymer. Herceptin, which specifically binds to HER2 antigen, was conjugated to the nanoparticles through click chemistry. The nanoparticles were characterized via dynamic light scattering (DLS) and transmission electron microscopy (TEM). Both methods showed the sizes of about 100nm with a uniform size distribution. The pH sensitivity was assessed by drug releases and size changes at different pH conditions. As pH decreased from 7.4 to 5.2, the drug release rate accelerated and the size significantly increased. During in vitro tests against human breast cancer cell lines, MCF-7 and SK-BR-3 showed significantly increased uptake for Herceptin-conjugated nanoparticles, as compared to non-targeted nanoparticles. Herceptin-conjugated pH-sensitive nanoparticles showed the highest therapeutic effect, and thus validated the efficacy of a combined approach of pH sensitivity and active targeting.

  7. Subcutaneously Administered Ultrafine PLGA Nanoparticles Containing Doxycycline Hydrochloride Target Lymphatic Filarial Parasites.

    PubMed

    Singh, Yuvraj; Srinivas, Adepu; Gangwar, Mamta; Meher, Jaya Gopal; Misra-Bhattacharya, Shailja; Chourasia, Manish K

    2016-06-06

    Systemic chemotherapeutic targeting of filarial parasites is unfocused due to their deep seated location in lymphatic vessels. This warrants a prolonged dosing regimen in high doses for an anthelmintic like doxycycline hydrochloride (DOX). In order to provide an alternative, we have constructed ultrafine PLGA nanoparticles of DOX (DPNPs), so as to exploit the peculiarity of lymphatic vasculature underneath the subcutaneous layer of skin, which preferentially allows entry of only 10-100 nm sized particles. DPNPs were constructed using a novel solvent diffusion method aided by probe sonication, which resulted in an average size 95.43 ± 0.8 nm as per DLS, PDI 0.168 ± 0.03, zeta potential -7.38 ± 0.32, entrapment efficiency 75.58 ± 1.94%, and refrigerator stability of 7 days with respect to size in the optimized batch. TEM further substantiated the spherical shape of DPNPs along with their actual nonhydrated size as being well below 100 nm. FTIR analysis of DOX, dummy nanoparticles, and freeze-dried DPNPs revealed that the formulation step did not induce prominent changes in the chemical nature of DOX. The drug release was significantly altered (p < 0.05) with 64.6 ± 1.67% release in 48 h from DPNPs and was dictated by Fickian diffusion. Pharmacokinetic studies in Wistar rats further revealed that DPNPs caused a 16-fold prolongation in attainment of plasma Tmax and a 2-fold extension of elimination half-life (28.569 ± 1.27 h) at a dose of 5 mg/kg when compared to native drug (DOX solution) of the same strength. Contrastingly the trend was reversed in regional lymph nodes where Cmax for DPNPs (820 ± 84 ng/mg) was 4-fold greater, and lymphatic Tmax was attained in one-fourth of what was required for DOX solution. This size based preferential lymphatic targeting resulted in significantly greater in vivo antifilarial activity of DPNPs when compared to DOX solution as gauged by several parameters in Brugia malayi infected Mastomys coucha. Interestingly, the

  8. Docetaxel-loaded polylactic acid-co-glycolic acid nanoparticles: formulation, physicochemical characterization and cytotoxicity studies.

    PubMed

    Pradhan, Roshan; Poudel, Bijay Kumar; Ramasamy, Thiruganesh; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2013-08-01

    In the present study, we developed novel docetaxel (DTX)-loaded polylactic acid-co-glycolic acid (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate (SLS) and poloxamer 407, the anionic and non-ionic surfactants respectively for stabilization. The NPs were prepared by emulsification/solvent evaporation method. The combination of these surfactants at weight ratio of 1:0.5 was able to produce uniformly distributed small sized NPs and demonstrated the better stability of NP dispersion with high encapsulation efficiency (85.9 +/- 0.6%). The drug/polymer ratio and phase ratio were 2:10 and 1:10, respectively. The optimized formulation of DTX-loaded PLGA NPs had a particle size and polydispersity index of 104.2 +/- 1.5 nm and 0.152 +/- 0.006, respectively, which was further supported by TEM image. In vitro release study was carried out with dialysis membrane and showed 32% drug release in 192 h. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.481, which suggested the drug was released by anomalous or non-Fickian diffusion. In addition, DTX-loaded PLGA NPs in 72 h, displayed approximately 75% cell viability reduction at 10 microg/ml DTX concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of DTX into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.

  9. Humidity-dependent compression-induced glass transition of the air-water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA).

    PubMed

    Kim, Hyun Chang; Lee, Hoyoung; Jung, Hyunjung; Choi, Yun Hwa; Meron, Mati; Lin, Binhua; Bang, Joona; Won, You-Yeon

    2015-07-28

    Constant rate compression isotherms of the air-water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA) show a distinct feature of an exponential increase in surface pressure in the high surface polymer concentration regime. We have previously demonstrated that this abrupt increase in surface pressure is linked to the glass transition of the polymer film, but the detailed mechanism of this process is not fully understood. In order to obtain a molecular-level understanding of this behavior, we performed extensive characterizations of the surface mechanical, structural and rheological properties of Langmuir PLGA films at the air-water interface, using combined experimental techniques including the Langmuir film balance, X-ray reflectivity and double-wall-ring interfacial rheometry methods. We observed that the mechanical and structural responses of the Langmuir PLGA films are significantly dependent on the rate of film compression; the glass transition was induced in the PLGA film only at fast compression rates. Surprisingly, we found that this deformation rate dependence is also dependent on the humidity of the environment. With water acting as a plasticizer for the PLGA material, the diffusion of water molecules through the PLGA film seems to be the key factor in the determination of the glass transformation properties and thus the mechanical response of the PLGA film against lateral compression. Based on our combined results, we hypothesize the following mechanism for the compression-induced glass transformation of the Langmuir PLGA film; (1) initially, a humidified/non-glassy PLGA film is formed in the full surface-coverage region (where the surface pressure shows a plateau) during compression; (2) further compression leads to the collapse of the PLGA chains and the formation of new surfaces on the air side of the film, and this newly formed top layer of the PLGA film is transiently glassy in character because the water evaporation rate

  10. Optimization of ciprofloxacin complex loaded PLGA nanoparticles for pulmonary treatment of cystic fibrosis infections: Design of experiments approach.

    PubMed

    Günday Türeli, Nazende; Türeli, Akif Emre; Schneider, Marc

    2016-12-30

    Design of Experiments (DoE) is a powerful tool for systematic evaluation of process parameters' effect on nanoparticle (NP) quality with minimum number of experiments. DoE was employed for optimization of ciprofloxacin loaded PLGA NPs for pulmonary delivery against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lungs. Since the biofilm produced by bacteria was shown to be a complicated 3D barrier with heterogeneous meshes ranging from 100nm to 500nm, nanoformulations small enough to travel through those channels were assigned as target quality. Nanoprecipitation was realized utilizing MicroJet Reactor (MJR) technology based on impinging jets principle. Effect of MJR parameters flow rate, temperature and gas pressure on particle size and PDI was investigated using Box-Behnken design. The relationship between process parameters and particle quality was demonstrated by constructed fit functions (R(2)=0.9934 p<0.0001 and R(2)=0.9983 p<0.0001, for particle size and PDI, respectively). Prepared nanoformulations varied between 145.2 and 979.8nm with PDI ranging from 0.050 to 1.00 and showed encapsulation efficiencies >65%. Response surface plots provided experimental data-based understanding of MJR parameters' effect, thus NP quality. Presented work enables ciprofloxacin loaded PLGA nanoparticle preparations with pre-defined quality to fulfill the requirements of local drug delivery under CF disease conditions.

  11. Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery

    PubMed Central

    Xin, Yu; Liu, Tie; Yang, Chenlong

    2016-01-01

    We have prepared novel poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 μg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold (t1/2), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with

  12. Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery.

    PubMed

    Xin, Yu; Liu, Tie; Yang, Chenlong

    We have prepared novel poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 μg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold (t1/2), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with

  13. Preliminary evaluation of the encapsulation of new antidiabetic sulphonylhydrazone and antitumor N-acylhydrazone derivatives using PLGA nanoparticles

    NASA Astrophysics Data System (ADS)

    Costa, F. N.; Ibiapino, A. L.; de Figueiredo, L. P.; Barreiro, E. J.; Lima, L. M.; do Amaral, D. N.; de Castro, C. E.; Giacomelli, F. C.; Ferreira, F. F.

    2015-05-01

    It has been demonstrated the feasibly of using PLGA nanoparticles to promote the encapsulation of novel anti-diabetic sulphonylhydrazone and antitumor N-acylhydrazone derivatives. The motivation is to further demonstrate the possibility of long-term release of anti-diabetic as well as higher accumulation of the antitumor derivative by using the nanotechnology-based production. The produced nanoparticles were obtained by the nanoprecipitation method, which revealed to be effective in the encapsulation of the bioactive compounds. The determined sizes were in the range of ∼100 nm, which are supposed to be suitable for both potential applications. The preliminary experimental data demonstrated the formation of stable nanosystems and further experiments are underway in order to determine the loading content, encapsulation efficiency and release profile of the hydrophobic bioactive compounds.

  14. 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.

  15. PLGA (85:15) nanoparticle based delivery of rL7/L12 ribosomal protein in mice protects against Brucella abortus 544 infection: A promising alternate to traditional adjuvants.

    PubMed

    Singh, Damini; Somani, Vikas Kumar; Aggarwal, Somya; Bhatnagar, Rakesh

    2015-12-01

    There is a compelling need for the development of suitable adjuvants for human use to enhance the efficacy of the upcoming vaccines for the prevention of life threatening infections. In the current study, we have tried to explore the immunogenic potential of nanoparticles (NPs) made of PLGA (poly lactic-co-glycolic acid), a biodegradable and biocompatible polymer approved by FDA for human use after entrapping rL7/L12 protein, an immunodominant antigen of Brucella. Adjuvant properties were exhibited by the formulation as it elicited high IgG antibody titers just after first immunization which increased significantly after the booster administration. A good elicitation of the Th1 cytokines especially IFN-γ was recorded. Amongst the IgG antibody subclasses, IgG1 remained the predominant subclass to be elicited in mice serum after immunization; however IgG1/2a ratio showed a mixed profile of Th1/Th2 response. Lymphocyte proliferation assay as a marker of amplification in cellular immunity demonstrated that the splenocytes of the immunized mice had a high proliferation index with reference to the control, revealing that L7/L12 entrapping PLGA nanoparticles are potent inducer of inflammatory cell response indispensable to combat Brucella infection. Enumeration of splenic CFU after 14 days of infection with Brucella abortus 544 showed a significant reduction in log CFU of splenic bacteria in the vaccinated mice as compared to the control group. Therefore it is evident that PLGA nano formulations delivering the entrapped vaccine candidate in mice elicit specific humoral as well as cellular responses specific to the entrapped Brucella antigen. So there is much promise in this approach and this work by highlighting the adjuvant properties of the PLGA nanospheres will accelerate the development of improved vaccines safe for human as well as veterinary use.

  16. Potent Engineered PLGA Nanoparticles by Virtue of Exceptionally High Chemotherapeutic Loadings

    PubMed Central

    Enlow, Elizabeth M.; Luft, J. Christopher; Napier, Mary E.; DeSimone, Joseph M.

    2011-01-01

    Herein we report the fabrication of engineered poly(lactic acid-co-glycolic acid) nanoparticles via the PRINT® (Particle Replication In Non-wetting Templates) process with high and efficient loadings of docetaxel, up to 40% (w/w) with encapsulation efficiencies >90%. The PRINT process enables independent control of particle properties leading to a higher degree of tailorability than traditional methods. Particles with 40% loading display better in vitro efficacy than particles with lower loadings and the clinical formulation of docetaxel, Taxotere®. PMID:21265552

  17. Dimensionality reduction, and function approximation of poly(lactic-co-glycolic acid) micro- and nanoparticle dissolution rate.

    PubMed

    Ojha, Varun Kumar; Jackowski, Konrad; Abraham, Ajith; Snášel, Václav

    2015-01-01

    Prediction of poly(lactic-co-glycolic acid) (PLGA) micro- and nanoparticles' dissolution rates plays a significant role in pharmaceutical and medical industries. The prediction of PLGA dissolution rate is crucial for drug manufacturing. Therefore, a model that predicts the PLGA dissolution rate could be beneficial. PLGA dissolution is influenced by numerous factors (features), and counting the known features leads to a dataset with 300 features. This large number of features and high redundancy within the dataset makes the prediction task very difficult and inaccurate. In this study, dimensionality reduction techniques were applied in order to simplify the task and eliminate irrelevant and redundant features. A heterogeneous pool of several regression algorithms were independently tested and evaluated. In addition, several ensemble methods were tested in order to improve the accuracy of prediction. The empirical results revealed that the proposed evolutionary weighted ensemble method offered the lowest margin of error and significantly outperformed the individual algorithms and the other ensemble techniques.

  18. Robust aptamer-polydopamine-functionalized M-PLGA-TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy.

    PubMed

    Xu, Guojun; Yu, Xinghua; Zhang, Jinxie; Sheng, Yingchao; Liu, Gan; Tao, Wei; Mei, Lin

    2016-01-01

    One limitation of current biodegradable polymeric nanoparticles (NPs) is the contradiction between functional modification and maintaining formerly excellent bioproperties with simple procedures. Here, we reported a robust aptamer-polydopamine-functionalized mannitol-functionalized poly(lactide-co-glycolide) (M-PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoformulation (Apt-pD-NPs) for the delivery of docetaxel (DTX) with enhanced cervical cancer therapy effects. The novel DTX-loaded Apt-pD-NPs possess satisfactory advantages: 1) increased drug loading content and encapsulation efficiency induced by star-shaped copolymer M-PLGA-TPGS; 2) significant active targeting effect caused by conjugated AS1411 aptamers; and 3) excellent long-term compatibility by incorporation of TPGS. Therefore, with simple preparation procedures and excellent bioproperties, the new functionalized Apt-pD-NPs could maximally increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. In a word, the robust DTX-loaded Apt-pD-NPs could be used as potential nanotherapeutics for cervical cancer treatment, and the aptamer-polydopamine modification strategy could be a promising method for active targeting of cancer therapy with simple procedures.

  19. Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment

    PubMed Central

    Zhang, Zhen; Qian, Hanqing; Yang, Mi; Li, Rutian; Hu, Jing; Li, Li; Yu, Lixia; Liu, Baorui; Qian, Xiaoping

    2017-01-01

    Gambogic acid (GA) is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid) (PLGA) with red blood-cell membrane (RBCm), and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier. PMID:28280328

  20. Synthesis and characterization of the antitubercular phenazine lapazine and development of PLGA and PCL nanoparticles for its entrapment.

    PubMed

    Silveira, Narjara; Longuinho, Mariana M; Leitão, Suzana G; Silva, Raphael S F; Lourenço, Maria C; Silva, Pedro E A; Pinto, Maria do Carmo F R; Abraçado, Leida G; Finotelli, Priscilla V

    2016-01-01

    The aim of this work was to develop and characterize nanoparticles as carriers of lapazine, a phenazine derived from β-lapachone; its antimycobacterial activity is described for the first time as a potential treatment for tuberculosis. The lapazine was synthesized, and by using gas chromatography coupled to a flame ionization detector, it was possible to evaluate its purity degree of almost 100%. For better elucidation of the molecular structure, mass spectroscopy and 1H NMR were carried out and compared to the literature values. Lapazine was assayed in vitro against H37Rv Mycobacterium tuberculosis and a rifampicin-resistant strain, with minimum inhibitory concentration values of 3.00 and 1.56 μg mL(-1), respectively. The nanoparticles showed a polydispersity index of 0.16,mean diameter of 188.5 ± 1.7 mm, zeta potential of -15.03 mV, and drug loading of 54.71 mg g(-1) for poly-ε-caprolactone (PCL) nanoparticles and a polydispersity index of 0.318,mean diameter of 197.4 ± 2.7 mm, zeta potential of -13.43 mV and drug loading of 137.07 mg g(-1) for poly(DL-lactide-co-glycolide) (PLGA) nanoparticles. These results indicate that both polymeric formulations have good characteristics as potential lapazine carriers in the treatment of tuberculosis.

  1. Vincristine and ɛ-viniferine-loaded PLGA-b-PEG nanoparticles: pharmaceutical characteristics, cellular uptake and cytotoxicity.

    PubMed

    Öğünç, Yüksel; Demirel, Müzeyyen; Yakar, Arzu; İncesu, Zerrin

    2017-02-02

    The objective of this study was to prepare the ɛ-viniferine and vincristine-loaded PLGA-b-PEG nanoparticle and to investigate advantages of these formulations on the cytotoxicity of HepG2 cells. Prepared nanoparticle has shown a homogeneous distribution with 113 ± 0.43 nm particle size and 0.323 ± 0.01 polydispersity index. Zeta potential was determined as -35.03 ± 1.0 mV. The drug-loading percentages were 6.01 ± 0.23 and 2.01 ± 0.07 for ɛ-viniferine and vincristine, respectively. The cellular uptake efficiency of coumarin-6-loaded nanoparticles was increased up to 87.8% after 4 h. Nanoparticles loaded with high concentrations of both drugs showed a cytotoxic effect on HepG2 cells, having the percentage of cell viability of between 43.23% and 47.37%. Unfortunately, the percentage of apoptotic cells after treated with drugs-loaded nanaoparticles (10.93%) was similar to free forms of drugs (12.1%) that might be due to low ɛ-viniferine release in biological pH at 24 h.

  2. HPLC-UV method development and validation for the quantification of ropinirole in new PLGA multiparticulate systems: Microspheres and nanoparticles.

    PubMed

    Fuster, J; Negro, S; Salama, A; Fernández-Carballido, A; Marcianes, P; Boeva, L; Barcia, E

    2015-08-01

    A simple HPLC-UV method was developed and validated for the quantitation of RP free base encapsulated into two new multiparticulate systems (microparticles and nanoparticles), as well as for the quantification of RP hydrochloride when given as a loading dose together with the new delivery system developed. HPLC separation was achieved using a C18 Kromasil column (250 mm × 4 mm) with a mobile phase composed of acetonitrile-phosphate buffer solution (55:45, v/v) adjusted at pH 6.0 and containing 0.3% triethanolamine. Flow rate was set at 1.0 mL min(-1). The UV detector was operated at 245 nm. The method allowed for the simultaneous determination of both RP and RP-HCl. The method was linear within the range 2.5-50 μg mL(-1) for both RP and RP-HCl. The limits of detection (LOD) and quantitation (LOQ) found were 0.8 μg mL(-1) and 2.4 μg mL(-1) for RP, and 0.3 μg mL(-1) and 0.9 μg mL(-1) for RP-HCl. The method was found to be simple, rapid, specific, precise, accurate, and reproducible. The method was successfully applied to the determination of the encapsulation efficiency of RP in the multiparticulate systems developed, being 85.03 ± 3.77% and 51.12 ± 3.50%, for RP-loaded PLGA microspheres and RP-loaded PLGA nanoparticles, respectively.

  3. Effects of Chrysin-PLGA-PEG Nanoparticles on Proliferation and Gene Expression of miRNAs in Gastric Cancer Cell Line

    PubMed Central

    Mohammadian, Farideh; Abhari, Alireza; Dariushnejad, Hassan; Nikanfar, Alireza; Pilehvar-Soltanahmadi, Younes; Zarghami, Nosratollah

    2016-01-01

    Background Recently, Chrysin, as a flavone, has revealed cancer chemo-preventive activity. The present experiment utilized the PLGA-PEG-chrysin complex, and free chrysin, to evaluation of the expression of miR-22, miR-34a and miR-126 in human gastric cell line. Objectives The purpose of this study was to examine whether nano encapsulating chrysin improves the anti-cancer effect of free chrysin on AGS human gastric cell line. Methods Properties of the chrysin encapsulated in PLGA-PEG nanoparticles were investigated by SEM, H NMR, and FTIR. The assessment of cytotoxicity on the growth of the human gastric cell line was carried out through MTT assay. After treating the cells with a prearranged amount of pure and encapsulated chrysin, RNA was extracted and the expressions of miR-22, miR-34a and miR-126 were measured by using real-time PCR. Results With regard to the amount of the chrysin loaded in PLGA-PEG nanoparticles, IC50 value was significantly decreased in nanocapsulatedchrysin, in comparison with free chrysin. This finding has been proved through the further increase of miR-22, miR-34a and miR-126 gene expression of nanocapsulatedchrysin, in comparison with free chrysin. Conclusions In this study, we revealed that the PLGA-PEG-chrysin is more effective than free chrysin in inhibiting the growth of human gastric cell line. PMID:27761206

  4. Detection of PLGA-based nanoparticles at a single-cell level by synchrotron radiation FTIR spectromicroscopy and correlation with X-ray fluorescence microscopy

    PubMed Central

    Pascolo, Lorella; Bortot, Barbara; Benseny-Cases, Nuria; Gianoncelli, Alessandra; Tosi, Giovanni; Ruozi, Barbara; Rizzardi, Clara; De Martino, Eleonora; Vandelli, Maria Angela; Severini, Giovanni Maria

    2014-01-01

    Poly-lactide-co-glycolide (PLGA) is one of the few polymers approved by the US Food and Drug Administration as a carrier for drug administration in humans; therefore, it is one of the most used materials in the formulation of polymeric nanoparticles (NPs) for therapeutic purposes. Because the cellular uptake of polymeric NPs is a hot topic in the nanomedicine field, the development of techniques able to ensure incontrovertible evidence of the presence of NPs in the cells plays a key role in gaining understanding of their therapeutic potential. On the strength of this premise, this article aims to evaluate the application of synchrotron radiation-based Fourier transform infrared spectroscopy (SR-FTIR) spectromicroscopy and SR X-ray fluorescence (SR-XRF) microscopy in the study of the in vitro interaction of PLGA NPs with cells. To reach this goal, we used PLGA NPs, sized around 200 nm and loaded with superparamagnetic iron oxide NPs (PLGA-IO-NPs; Fe3O4; size, 10–15 nm). After exposing human mesothelial (MeT5A) cells to PLGA-IO-NPs (0.1 mg/mL), the cells were analyzed after fixation both by SR-FTIR spectromicroscopy and SR-XRF microscopy setups. SR-FTIR-SM enabled the detection of PLGA NPs at single-cell level, allowing polymer detection inside the biological matrix by the characteristic band in the 1,700–2,000 cm−1 region. The precise PLGA IR-signature (1,750 cm−1 centered pick) also was clearly evident within an area of high amide density. SR-XRF microscopy performed on the same cells investigated under SR-FTIR microscopy allowed us to put in evidence the Fe presence in the cells and to emphasize the intracellular localization of the PLGA-IO-NPs. These findings suggest that SR-FTIR and SR-XRF techniques could be two valuable tools to follow the PLGA NPs’ fate in in vitro studies on cell cultures. PMID:24944512

  5. Detection of PLGA-based nanoparticles at a single-cell level by synchrotron radiation FTIR spectromicroscopy and correlation with X-ray fluorescence microscopy.

    PubMed

    Pascolo, Lorella; Bortot, Barbara; Benseny-Cases, Nuria; Gianoncelli, Alessandra; Tosi, Giovanni; Ruozi, Barbara; Rizzardi, Clara; De Martino, Eleonora; Vandelli, Maria Angela; Severini, Giovanni Maria

    2014-01-01

    Poly-lactide-co-glycolide (PLGA) is one of the few polymers approved by the US Food and Drug Administration as a carrier for drug administration in humans; therefore, it is one of the most used materials in the formulation of polymeric nanoparticles (NPs) for therapeutic purposes. Because the cellular uptake of polymeric NPs is a hot topic in the nanomedicine field, the development of techniques able to ensure incontrovertible evidence of the presence of NPs in the cells plays a key role in gaining understanding of their therapeutic potential. On the strength of this premise, this article aims to evaluate the application of synchrotron radiation-based Fourier transform infrared spectroscopy (SR-FTIR) spectromicroscopy and SR X-ray fluorescence (SR-XRF) microscopy in the study of the in vitro interaction of PLGA NPs with cells. To reach this goal, we used PLGA NPs, sized around 200 nm and loaded with superparamagnetic iron oxide NPs (PLGA-IO-NPs; Fe₃O₄; size, 10-15 nm). After exposing human mesothelial (MeT5A) cells to PLGA-IO-NPs (0.1 mg/mL), the cells were analyzed after fixation both by SR-FTIR spectromicroscopy and SR-XRF microscopy setups. SR-FTIR-SM enabled the detection of PLGA NPs at single-cell level, allowing polymer detection inside the biological matrix by the characteristic band in the 1,700-2,000 cm(-1) region. The precise PLGA IR-signature (1,750 cm(-1) centered pick) also was clearly evident within an area of high amide density. SR-XRF microscopy performed on the same cells investigated under SR-FTIR microscopy allowed us to put in evidence the Fe presence in the cells and to emphasize the intracellular localization of the PLGA-IO-NPs. These findings suggest that SR-FTIR and SR-XRF techniques could be two valuable tools to follow the PLGA NPs' fate in in vitro studies on cell cultures.

  6. Evaluation of anti-HER2 scFv-conjugated PLGA-PEG nanoparticles on 3D tumor spheroids of BT474 and HCT116 cancer cells

    NASA Astrophysics Data System (ADS)

    Thuy Duong Le, Thi; Pham, Thu Hong; Nghia Nguyen, Trong; Giang Ngo, Thi Hong; Nhung Hoang, Thi My; Huan Le, Quang

    2016-06-01

    Three-dimensional culture cells (spheroids) are one of the multicellular culture models that can be applied to anticancer chemotherapeutic development. Multicellular spheroids more closely mimic in vivo tumor-like patterns of physiologic environment and morphology. In previous research, we designed docetaxel-loaded pegylated poly(D, L-lactide-co-glycolide) nanoparticles conjugated with anti-HER2 single chain antibodies (scFv-Doc-PLGA-PEG) and evaluated them in 2D cell culture. In this study, we continuously evaluate the cellular uptake and cytotoxic effect of scFv-Doc-PLGA-PEG on a 3D tumor spheroid model of BT474 (HER2-overexpressing) and HCT116 (HER2-underexpressing) cancer cells. The results showed that the nanoparticle formulation conjugated with scFv had a significant internalization effect on the spheroids of HER2-overexpressing cancer cells as compared to the spheroids of HER2-underexpressing cancer cells. Therefore, cytotoxic effects of targeted nanoparticles decreased the size and increased necrotic score of HER2-overexpressing tumor spheroids. Thus, these scFv-Doc-PLGA-PEG nanoparticles have potential for active targeting for HER2-overexpressing cancer therapy. In addition, BT474 and HCT116 spheroids can be used as a tumor model for evaluation of targeting therapies.

  7. Biodegradable PLGA85/15 nanoparticles as a delivery vehicle for Chlamydia trachomatis recombinant MOMP-187 peptide

    NASA Astrophysics Data System (ADS)

    Taha, Murtada A.; Singh, Shree R.; Dennis, Vida A.

    2012-08-01

    Development of a Chlamydia trachomatis vaccine has been a formidable task partly because of an ineffective delivery system. Our laboratory has generated a recombinant peptide of C. trachomatis major outer membrane protein (MOMP) (rMOMP-187) and demonstrated that it induced at 20 μg ml-1 maximal interleukin (IL)-6 and IL-12p40 Th1 cytokines in mouse J774 macrophages. In a continuous pursuit of a C. trachomatis effective vaccine-delivery system, we encapsulated rMOMP-187 in poly(d,l-lactic-co-glycolic acid) (PLGA, 85:15 PLA/PGA ratio) to serve as a nanovaccine candidate. Physiochemical characterizations were assessed by Fourier transform-infrared spectroscopy, atomic force microscopy, Zetasizer, Zeta potential, transmission electron microcopy and differential scanning calorimetry. The encapsulated rMOMP-187 was small (˜200 nm) with an apparently smooth uniform oval structure, thermally stable (54 °C), negatively charged ( - 27.00 mV) and exhibited minimal toxicity at concentrations <250 μg ml -1 to eukaryotic cells (>95% viable cells) over a 24-72 h period. We achieved a high encapsulation efficiency of rMOMP-187 (˜98%) in PLGA, a loading peptide capacity of 2.7% and a slow release of the encapsulated peptide. Stimulation of J774 macrophages with a concentration as low as 1 μg ml -1 of encapsulated rMOMP-187 evoked high production levels of the Th1 cytokines IL-6 (874 pg ml-1) and IL-12p40 (674 pg ml-1) as well as nitric oxide (8 μM) at 24 h post-stimulation, and in a dose-response and time-kinetics manner. Our data indicate the successful encapsulation and characterization of rMOMP-187 in PLGA and, more importantly, that PLGA enhanced the capacity of the peptide to induce Th1 cytokines and NO in vitro. These findings make this nanovaccine an attractive candidate in pursuit of an efficacious vaccine against C. trachomatis.

  8. Measurement of PLGA-NP interaction with single smooth muscle cells using optical tweezers

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Mondal, Argha; Homayoni, Homa; Nguyen, Kytai; Mohanty, Samarendra

    2012-10-01

    For intervention of cardiovascular diseases, biodegradable and biocompatible, poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) are emerging as agents of choice for controlled and targeted drug delivery. Therefore development of PLGA-NP with optimal physico-chemical properties will allow efficient binding and thus delivery of drug to targeted cells under various patho-physiological conditions. The force kinetics and its dependence on size of the NPs will be crucial for designing the NPs. Since optical tweezers allow non-contact, highly sensitive force measurement with high spatial and temporal resolution, we utilized it for studying interaction forces between magnetic PLGA nanoparticles with smooth muscle cells (SMC). In order to investigate effect of size, interaction force for 200 to 1100nm PLGA NP was measured. For similar interaction duration, the force was found to be higher with increase in size. The rupture force was found to depend on time of interaction of SMC with NPs.

  9. Poly(lactic-co-glycolic) Acid/Solutol HS15-Based Nanoparticles for Docetaxel Delivery.

    PubMed

    Cho, Hyun-Jong; Park, Ju-Hwan; Kim, Dae-Duk; Yoon, In-Soo

    2016-02-01

    Docetaxel (DCT) is one of anti-mitotic chemotherapeutic agents and has been used for the treatment of gastric cancer as well as head and neck cancer, breast cancer and prostate cancer. Poly(lactic- co-glycolic) acid (PLGA) is one of representative biocompatible and biodegradable polymers, and polyoxyl 15 hydroxystearate (Solutol HS15) is a nonionic solubilizer and emulsifying agent. In this investigation, PLGA/Solutol HS15-based nanoparticles (NPs) for DCT delivery were fabricated by a modified emulsification-solvent evaporation method. PLGA/Solutol HS15/DCT NPs with about 169 nm of mean diameter, narrow size distribution, negative zeta potential, and spherical morphology were prepared. The results of solid-state studies revealed the successful dispersion of DCT in PLGA matrix and its amorphization during the preparation process of NPs. According to the result of in vitro release test, emulsifying property of Solutol HS15 seemed to contribute to the enhanced drug release from NPs at physiological pH. All these findings imply that developed PLGA/Solutol HS15-based NP can be a promising local anticancer drug delivery system for cancer therapy.

  10. Impact of poly(lactic-co-glycolic acid) nanoparticle surface charge on protein, cellular and haematological interactions.

    PubMed

    Pillai, Gopikrishna J; Greeshma, M M; Menon, Deepthy

    2015-12-01

    The initial interactions of nanoparticles with biomolecules have a great influence on its toxicity, efficacy, biodistribution and clearance. The present work is an attempt to understand the impact of surface charge of polymeric nanoparticles on its plasma protein and cellular interactions. Negative, near-neutral and positively charged poly(lactic-co-glycolic acid) [PLGA] nanoparticles were prepared using casein, poly(vinyl alcohol) and poly(ethylene imine) respectively, as surface stabilizers. A significant temporal variation in the hydrodynamic diameter of PLGA nanoparticles was observed in the presence of plasma proteins, which correlated with the amount of proteins adsorbed to each surface. Positively charged particles displayed the maximum size variation and protein adsorption. Cellular uptake of differentially charged nanoparticles was also concurrent with the quantity of adsorbed proteins, though there was no significant difference in their cytotoxicity. Haematological interactions (haemolysis and plasma coagulation times) of positively charged nanoparticles were considerably different from near-neutral and negative nanoparticles. Collectively, the results point to the interplay between plasma protein adsorption and cellular interactions of PLGA nanoparticles, which is governed by its surface charge, thereby necessitating a rational design of nanoparticles.

  11. Nanostructured medical device coatings based on self-assembled poly(lactic-co-glycolic acid) nanoparticles.

    PubMed

    Dayyoub, Eyas; Hobler, Christian; Nonnweiler, Pierina; Keusgen, Michael; Bakowsky, Udo

    2013-07-01

    Here we present a new method for providing nanostructured drug-loaded polymer films which enable control of film surface morphology and delivery of therapeutic agents. Silicon wafers were employed as models for implanted biomaterials and poly(lactic-co-glycolic acid) (PLGA) nanoparticles were assembled onto the silicon surface by electrostatic interaction. Monolayers of the PLGA particles were deposited onto the silicon surface upon incubation in an aqueous particle suspension. Particle density and surface coverage of the silicon wafers were varied by altering particle concentration, incubation time in nanoparticle suspension and ionic strength of the suspension. Dye loaded nanoparticles were prepared and assembled to silicon surface to form nanoparticle films. Fluorescence intensity measurements showed diffusion-controlled release of the dye over two weeks and atomic force microscopy (AFM) analysis revealed that these particles remained attached to the surface during the incubation time. This work suggests that coating implants with PLGA nanoparticles is a versatile technique which allows drug release from the implant surface and modulation of surface morphology.

  12. Wheat germ agglutinin-conjugated PLGA nanoparticles for enhanced intracellular delivery of paclitaxel to colon cancer cells.

    PubMed

    Wang, Chunxia; Ho, Paul C; Lim, Lee Yong

    2010-11-15

    The purpose of this study was to investigate the potentiation of the anticancer activity and enhanced cellular retention of paclitaxel-loaded PLGA nanoparticles after surface conjugation with wheat germ agglutinin (WGA) against colon cancer cells. Glycosylation patterns of representative colon cancer cells confirmed the higher expression levels of WGA-binding glycoproteins in the Caco-2 and HT-29 cells, than in the CCD-18Co cells. Cellular uptake and in vitro cytotoxicity of WNP (final formulation) against colon cell lines was evaluated alongside control formulations. Confocal microscopy and quantitative analysis of intracellular paclitaxel were used to monitor the endocytosis and retention of nanoparticles inside the cells. WNP showed enhanced anti-proliferative activity against Caco-2 and HT-29 cells compared to corresponding nanoparticles without WGA conjugation (PNP). The greater efficacy of WNP was associated with higher cellular uptake and sustained intracellular retention of paclitaxel, which in turn was attributed to the over-expression of N-acetyl-D-glucosamine-containing glycoprotein on the colon cell membrane. WNP also demonstrated increased intracellular retention in the Caco-2 (30% of uptake) and HT-29 (40% of uptake) cells, following post-uptake incubation with fresh medium, compared to the unconjugated PNP nanoparticles (18% in Caco-2) and (27% in HT-29), respectively. Cellular trafficking study of WNP showed endocytosed WNP could successful escape from the endo-lysosome compartment and release into the cytosol with increasing incubation time. It may be concluded that WNP has the potential to be applied as a targeted delivery platform for paclitaxel in the treatment of colon cancer.

  13. Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo.

    PubMed

    Qiao, Chunyan; Zhang, Kai; Jin, Han; Miao, Leiying; Shi, Ce; Liu, Xia; Yuan, Anliang; Liu, Jinzhong; Li, Daowei; Zheng, Changyu; Zhang, Guirong; Li, Xiangwei; Yang, Bai; Sun, Hongchen

    2013-01-01

    Repair of large bone defects is a major challenge, requiring sustained stimulation to continually promote bone formation locally. Bone morphogenetic protein 2 (BMP-2) plays an important role in bone development. In an attempt to overcome this difficulty of bone repair, we created a delivery system to slowly release human BMP-2 cDNA plasmid locally, efficiently transfecting local target cells and secreting functional human BMP-2 protein. For transfection, we used polyethylenimine (PEI) to create pBMP-2/PEI nanoparticles, and to ensure slow release we used poly(lactic-co-glycolic acid) (PLGA) to create microsphere encapsulated pBMP-2/PEI nanoparticles, PLGA@pBMP-2/PEI. We demonstrated that pBMP-2/PEI nanoparticles could slowly release from the PLGA@pBMP-2/PEI microspheres for a long period of time. The 3-15 μm diameter of the PLGA@pBMP-2/PEI further supported this slow release ability of the PLGA@pBMP-2/PEI. In vitro transfection assays demonstrated that pBMP-2/PEI released from PLGA@pBMP-2/PEI could efficiently transfect MC3T3-E1 cells, causing MC3T3-E1 cells to secrete human BMP-2 protein, increase calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7 and I type collagen (COLL I), and finally induce MC3T3-E1 cell differentiation. Importantly, in vivo data from micro-computed tomography (micro-CT) and histological staining demonstrated that the human BMP-2 released from PLGA@pBMP-2/PEI had a long-term effect locally and efficiently promoted bone formation in the bone defect area compared to control animals. All our data suggest that our PLGA-nanoparticle delivery system efficiently and functionally delivers the human BMP-2 cDNA and has potential clinical application in the future after further modification.

  14. 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.

  15. Poly(lactic-co-glycolic acid) nanoparticles as candidate DNA vaccine carrier for oral immunization of Japanese flounder (Paralichthys olivaceus) against lymphocystis disease virus.

    PubMed

    Tian, Jiyuan; Yu, Juan

    2011-01-01

    In order to protect DNA vaccine against degradation in alimentary tract of fish, poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating vaccine were prepared using W/O/W emulsification combined with spray drying technique in our laboratory. The characteristics of PLGA nanoparticles were described as follows: (1) shape, spherical; (2) size, <500 nm; (3) yield, ∼96.2%; loading percentage, ∼0.5%; encapsulation efficiency, ∼63.7%; supercoiled conformation percentage, ∼65%; (4) release dynamics, gradual release. In vitro transfection in SISK cells showed that PLGA nanoparticles could be utilized to transfect eukaryotes. After oral administration, FITC-labeled PLGA nanoparticles were detected in blood of fish, and RNA containing major capsid protein (MCP) gene information existed in various tissues of fish 10-90 days. In addition, the analysis of immune parameters in sera of treatment fish showed that: (1) infection rate of LCDV post-challenge, ∼16.7%; (2) prophenoloxidase, superoxide dismutase, respiratory burst, lysozyme and antibody levels, increased significantly (p<0.05); (3) activities of serum complement, changed a little (p>0.05). Pearson's correlation displayed that correlation of immune factors mentioned above (not including serum complement) were all positive for fish vaccinated. The data in this study suggested that PLGA nanoparticles were promising carriers for plasmid DNA vaccine and might be used to vaccinate fish by oral approach.

  16. Chitosan-coated poly(lactic-co-glycolic) acid nanoparticles as an efficient delivery system for Newcastle disease virus DNA vaccine.

    PubMed

    Zhao, Kai; Zhang, Yang; Zhang, Xiaoyan; Shi, Ci; Wang, Xin; Wang, Xiaohua; Jin, Zheng; Cui, Shangjin

    2014-01-01

    We determined the efficacy and safety of chitosan (CS)-coated poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) as a delivery system for a vaccine to protect chickens against Newcastle disease virus (NDV). The newly constructed vaccine contained DNA (the F gene) of NDV. The Newcastle disease virus (NDV) F gene deoxyribonucleic acid (DNA) plasmid (pFDNA)-CS/PLGA-NPs were spherical (diameter =699.1 ± 5.21 nm [mean ± standard deviation]) and smooth, with an encapsulation efficiency of 98.1% and a Zeta potential of +6.35 mV. An in vitro release assay indicated that CS controlled the burst release of plasmid DNA, such that up to 67.4% of the entire quantity of plasmid DNA was steadily released from the pFDNA-CS/PLGA-NPs. An in vitro expression assay indicated that the expression of nanoparticles (NPs) was maintained in the NPs. In an immunization test with specific pathogen-free chickens, the pFDNA-CS/PLGA-NPs induced stronger cellular, humoral, and mucosal immune responses than the plasmid DNA vaccine alone. The pFDNA-CS/PLGA-NPs did not harm 293T cells in an in vitro assay and did not harm chickens in an in vivo assay. Overall, the results indicated that CS-coated PLGA NPs can serve as an efficient and safe mucosal immune delivery system for NDV DNA vaccine.

  17. Antibody conjugated PLGA nanoparticles for targeted delivery of paclitaxel palmitate: efficacy and biofate in a lung cancer mouse model.

    PubMed

    Karra, Nour; Nassar, Taher; Ripin, Alina Nemirovski; Schwob, Ouri; Borlak, Jürgen; Benita, Simon

    2013-12-20

    Aberrant signaling of the epidermal growth factor receptor (EGFR) is common to a variety of human cancers and is also found to be over-expressed in most cases of non-small cell lung cancer. For the development of a molecularly targeted therapy, cetuximab-conjugated nanoparticles (immunonanoparticles, INPs) are designed and loaded with the lipophilic paclitaxel palmitate (pcpl) prodrug. Oleyl cysteineamide (OCA) is synthesized whereby its amphiphilic nature enables interfacial anchoring and thiol surface functionalization of PLGA NPs, facilitating bioconjugation to cetuximab by thioether bonds. It is demonstrated that the in vitro targeting efficiency and improved cellular internalization and cytotoxicity of this targeted delivery system in lung cancer cells over-expressing EGFR. A quantitative measure of the high binding affinity of INPs to EGFR is demonstrated using surface plasmon resonance. In vivo tolerability and enhanced efficacy of cetuximab pcpl INPs in a metastatic lung cancer model are reported. Its therapeutic efficacy in A549-luc-C8 lung tumors is shown using non-invasive bioluminescent imaging. Intravenous administration of cetuximab pcpl INPs to mice results in significantly higher inhibition of tumor growth and increased survival rates as compared to the non-targeted drug solution, drug-loaded nanoparticles or blank INPs. Pharmacokinetics and organ biodistribution of the prodrug and parent drug are evaluated by LC-MS/MS in lung tumor bearing mice. No enhanced total accumulation of nanoparticles or INPs is found at the tumor tissue. However, persistent pcpl levels with sustained conversion and release of paclitaxel are observed for the encapsulated prodrug possibly suggesting the formation of a drug reservoir. The overall results indicate the potential of this promising targeted platform for the improved treatment of lung cancer and other EGFR positive tumors.

  18. Treatment of bleomycin-induced pulmonary fibrosis by inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles.

    PubMed

    Lee, Changkyu; Seo, Jisoo; Hwang, Ha Shin; Thao, Le Quang; Lee, Seunghyun; Lee, Eun Seong; Lee, Eun Hee; Choi, Han-Gon; Youn, Yu Seok

    2016-03-01

    Pulmonary fibrosis is a chronic lung disease characterized by inflammation and collagen deposition, with an estimated mortality rate exceeding 70%. Here, we evaluated the therapeutic effectiveness of inhaled tacrolimus-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles (chitosan TAC PLGA-NPs) in a bleomycin-induced pulmonary fibrosis mouse model. Chitosan TAC PLGA-NPs were fabricated using an o/w emulsification diffusion method, and uncoated TAC PLGA-NPs and chitosan TAC PLGA-NPs were spherical with approximate diameters of 320 and 441 nm, respectively. The zeta potential of chitosan TAC PLGA-NPs (+13.6 mV) was increased significantly by chitosan-coating versus uncoated TAC PLGA-NPs (-28.3 mV). The incorporation efficiency of tacrolimus was 37.7%, and the tacrolimus was gradually released until about 5 day. Direct inhalation of chitosan TAC PLGA-NPs (TAC 180 μg/mouse) twice a week produced marked anti-fibrotic efficacy in mice with bleomycin-induced pulmonary fibrosis, which was much better than the efficacy resulting from daily oral administration (TAC 300 μg/mouse) on the basis of hematoxylin/eosin and Masson's trichrome staining assessments. Imaging of lung deposition showed that chitosan TAC PLGA-NPs were located well in the lungs and gradually faded over 96 h. The pulmonary delivery of tacrolimus could be therapeutically efficacious for treating pulmonary fibrosis. TAC-loaded PLGA nanoparticles should be considered to be an efficient sustained-release type inhalation system that reduces administration frequency and relevant side effects.

  19. Paclitaxel-loaded nanoparticles of star-shaped cholic acid-core PLA-TPGS copolymer for breast cancer treatment

    PubMed Central

    2013-01-01

    A system of novel nanoparticles of star-shaped cholic acid-core polylactide-d-α-tocopheryl polyethylene glycol 1000 succinate (CA-PLA-TPGS) block copolymer was developed for paclitaxel delivery for breast cancer treatment, which demonstrated superior in vitro and in vivo performance in comparison with paclitaxel-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles and linear PLA-TPGS nanoparticles. The paclitaxel- or couramin 6-loaded nanoparticles were fabricated by a modified nanoprecipitation method and then characterized in terms of size, surface charge, surface morphology, drug encapsulation efficiency, and in vitro drug release. The CA-PLA-TPGS nanoparticles were found to be spherical in shape with an average size of around 120 nm. The nanoparticles were found to be stable, showing no change in the particle size and surface charge during 90-day storage of the aqueous solution. The release profiles of the paclitaxel-loaded nanoparticles exhibited typically biphasic release patterns. The results also showed that the CA-PLA-TPGS nanoparticles have higher antitumor efficacy than the PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, such nanoparticles of star-shaped cholic acid-core PLA-TPGS block copolymer could be considered as a potentially promising and effective strategy for breast cancer treatment. PMID:24134303

  20. Enhancing the receptor-mediated cell uptake of PLGA nanoparticle for targeted drug delivery by incorporation chitosan onto the particle surface

    NASA Astrophysics Data System (ADS)

    Jiang, Guoqiang; Tang, Shifu; Chen, Xuelan; Ding, Fuxin

    2014-06-01

    Cationic polymer chitosan (CS) and target ligand were both incorporated onto nanoparticles (NPs) to enhance the cell uptake by integration of electrostatic interaction and receptor-mediated internalization. CS and biotin-contained amphipathic polymer biotin-poly(ethylene glycol)-poly(lactic acid) (biotin-PEG-PLA) were simultaneously decorated on the poly(lactic- co-glycolic acid) (PLGA) NPs surface in one step during the o/w solvent evaporation procedure. The incorporation of CS increased the zeta potential of the NPs to positive value and showed little impacts on particle size and biotin density. Cell uptake was investigated in vitro using human hepatic carcinoma cell lines SMMC-7721. The CS and biotin co-decorated NPs (CS-B-NPs) presented significantly higher cell uptake than that of the mono biotin-decorated NPs (B-NPs). In acid environment, as CS-B-NPs are more positive charged, cell uptake of CS-B-NPs is further increased, which is 3.8-fold as much as that of the undecorated NPs (U-NPs) and 1.9-fold higher than that of B-NPs at pH 6.6. When either the ligand density was reduced within limited or the particle size was slightly increased, cell uptake of CS-B-NPs remained almost the same. The cell uptake mechanism study demonstrated that the internalization due to the electrostatic interaction would contribute more to the cell uptake when the internalization based on clathrin-mediated endocytosis and other ATP-dependent pathways were blocked. The co-decoration of CS and target ligand is an effective approach for improving the specific cell uptake of NPs.

  1. Co-delivery of VEGF and bFGF via a PLGA nanoparticle-modified BAM for effective contracture inhibition of regenerated bladder tissue in rabbits

    NASA Astrophysics Data System (ADS)

    Jiang, Xincheng; Lin, Houwei; Jiang, Dapeng; Xu, Guofeng; Fang, Xiaoliang; He, Lei; Xu, Maosheng; Tang, Bingqiang; Wang, Zhiyong; Cui, Daxiang; Chen, Fang; Geng, Hongquan

    2016-02-01

    Graft contracture is a common problem associated with the regeneration processes of tissue-engineered bladders. Currently, most strategies used for incorporating bioactive molecules into biomaterial designs do not work during all phases of tissue regeneration. In this study, we used a growth factor-PLGA nanoparticle thermo-sensitive gel system (i.e., BAM with incorporated VEGF and bFGF-loaded PLGA nanoparticles and mixed with a hydrophilic gel) to promote bladder tissue regeneration in a rabbit model. At 4 and 12 weeks after surgery, contracture rate assessment and histological examination were conducted to evaluate bladder tissue regeneration. The results indicated that the functional composite scaffold continuously and effectively released VEGF and bFGF and promoted bladder reconstruction with a significant decrease in graft contracture. In addition, the number and arrangement of regenerated urothelial cells and smooth muscle cells as well as microvascular density and maturity were improved in the VEGF/bFGF nanoparticle group compared with the single factor VEGF or bFGF nanoparticle group and BAM alone. The nanoparticle thermo-sensitive gel system, which exhibited favourable performance, may effectively inhibit graft contracture and promote bladder tissue regeneration in rabbits.

  2. Enhanced delivery of Paclitaxel using electrostatically-conjugated Herceptin-bearing PEI/PLGA nanoparticles against HER-positive breast cancer cells.

    PubMed

    Yu, Kongtong; Zhao, Jinlong; Zhang, Zunkai; Gao, Yin; Zhou, Yulin; Teng, Lesheng; Li, Youxin

    2016-01-30

    We have developed a novel nanoparticle delivery system fabricated from polyethylenimine (PEI) and poly(d,l-lactide-co-glycolide) (PLGA), which were able to deliver the chemotherapeutic agent Paclitaxel, while the biomacromolecule Herceptin acted as a targeting ligand that was conjugated onto the surfaces of the nanoparticles via electrostatic interactions. In this study, these electrostatically-conjugated Herceptin-bearing PEI/PLGA nanoparticles (eHER-PPNs) were optimized and employed as vectors to target HER2-positive breast cancer cells. The eHER-PPNs had an average diameter of ∼ 280 nm and a neutral surface charge (1.00 ± 0.73 mV), which remained stable under physiological conditions. The anticancer effects of eHER-PPNs were investigated in HER2-positive BT474 cells and HER2-negative MCF7 cells. The eHER-PPNs showed enhanced cytotoxicity that was dependent on the receptor expression levels and the incubation time. These conjugated nanoparticles deliver Paclitaxel more efficiently (p<0.001) than unmodified PPNs, Herceptin and the combined effects of these two monotherapies. Furthermore, the chemically-conjugated Herceptin-bearing PEI/PLGA nanoparticles (cHER-PPNs) were fabricated as a comparison. The eHER-PPNs exhibited lower cell viability (46.7%) than that of cHER-PPNs (65.1%). The targeting ability of eHER-PPNs was demonstrated through confocal microscopy images and flow cytometry, which showed that eHER-PPNs displayed higher cellular uptake efficiency (p<0.001) in comparison with cHER-PPNs. Therefore, eHER-PPNs could provide promising platforms for the delivery of therapeutic drugs against HER2-positive breast cancers.

  3. PLGA nanoparticle entrapped killed porcine reproductive and respiratory syndrome virus vaccine helps in viral clearance in pigs.

    PubMed

    Dwivedi, Varun; Manickam, Cordelia; Binjawadagi, Basavaraj; Renukaradhya, Gourapura J

    2013-09-27

    Porcine reproductive and respiratory syndrome (PRRS) is a chronic viral disease of pigs, has been posing a huge economic concern to pig industry worldwide. In this study, we developed biodegradable PLGA [poly(d,l-lactide-co-glycolide)] nanoparticle-entrapped killed PRRSV vaccine (Nano-KAg), and administered intranasally to pigs once and evaluated the immune correlates. In Nano-KAg vaccinated homologous virus challenged pigs, complete clearance of viremia was observed in 2 weeks, associated with a significant increase in virus neutralizing titers only in the lungs, compared to both unvaccinated and killed vaccine vaccinated pigs. The lung homogenate and sera of Nano-KAg vaccinated pigs had higher levels of IFN-γ and lower levels of TGF-β than control groups. Restimulation of mononuclear cells isolated from the lungs, blood, BAL, and TBLN of Nano-KAg vaccinated pigs' secreted significantly increased levels of Th1 cytokines, IFN-γ and IL-12. In addition, higher frequencies of CD3(+)CD8(+), CD4(+)CD8(+), and γδ T cells, and reduced frequency of Foxp3(+) T-regulatory cells were observed in Nano-KAg vaccinated pigs. Thus, intranasal delivery of Nano-KAg vaccine may be a suitable strategy to elicit anti-PRRSV immune response required to better clear viremia in pigs.

  4. The synergic antitumor effects of paclitaxel and temozolomide co-loaded in mPEG-PLGA nanoparticles on glioblastoma cells

    PubMed Central

    Li, Yiming; Sun, Ying; Teng, Yanwei; Wang, Yi; Duan, Yourong

    2016-01-01

    To get better chemotherapy efficacy, the optimal synergic effect of Paclitaxel (PTX) and Temozolomide (TMZ) on glioblastoma cells lines was investigated. A dual drug-loaded delivery system based on mPEG-PLGA nanoparticles (NPs) was developed to potentiate chemotherapy efficacy for glioblastoma. PTX/TMZ-NPs were prepared with double emulsification solvent evaporation method and exhibited a relatively uniform diameter of 206.3 ± 14.7 nm. The NPs showed sustained release character. Cytotoxicity assays showed the best synergistic effects were achieved when the weight ratios of PTX to TMZ were 1:5 and 1:100 on U87 and C6 cells, respectively. PTX/TMZ-NPs showed better inhibition effect to U87 and C6 cells than single drug NPs or free drugs mixture. PTX/TMZ-NPs (PTX: TMZ was 1:5(w/w)) significantly inhibited the tumor growth in the subcutaneous U87 mice model. These results indicate that coordinate administration of PTX and TMZ combined with NPs is an efficient method for glioblastoma. PMID:26956046

  5. trans-[Ru(NO)Cl(cyclam)](PF6)2 and [Ru(NO)(Hedta)] incorporated in PLGA nanoparticles for the delivery of nitric oxide to B16-F10 cells: cytotoxicity and phototoxicity.

    PubMed

    Gomes, Anderson J; Espreafico, Enilza M; Tfouni, Elia

    2013-10-07

    The immobilization and characterization of trans-[Ru(NO)Cl(cyclam)](PF6)2 (cyclam=1,4,8,11-tetraazacyclotetradecane), and [Ru(NO)(Hedta)] (Hedta=ethylenediaminetetraacetic acid) entrapped in poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NP) using the double emulsification process is described. Scanning electron microscopy and dynamic light scattering revealed that the particles are spherical in shape, have a size distribution between 220 and 840 nm of diameter, and have a tendency to aggregate confirmed by a zeta potential between -3.2 and +3.5 mV. Using this method the loading efficiency was 26% for trans-[Ru(NO)Cl(cyclam)](PF6)2 and 32% for [Ru(NO)(Hedta)]. The release of the complexes from the NPs shows that cyclam-NP and Hedta-NP exhibited a two-phase exponential association release pattern, which was characterized by an initial complex burst during the first 24 h, followed by a slower release phase complex profile, due to a few pores observed in surface of nanoparticles using atomic force microscopy. The in vitro cytotoxic activity of the nitrosyl complexes in solution and incorporated in PLGA nanoparticles on melanoma cancer cells (cell line B16-F10) was investigated. The lower cytotoxicity of trans-[RuCl(cyclam)(NO)]2+ (12.4±2.6%) and [Ru(NO)(Hedta)] (4.0±2.7%) in solution compared to that of trans-[Ru(NO)(NH3)4py]3+ (46.1±6.4%) is consistent with the rate constant release of NO of these complexes (k-NO=6.2×10(-4) s(-1), 2.0×10(-3) s(-1), and 6.0×10(-2) s(-1), respectively); the cytotoxicities are also inhibited in the presence of the NO scavenger carboxy-PTIO. The phototoxicity of these complexes is due to NO release, which lead to 53.8±6.2% of cell death in the presence of trans-[Ru(NO)Cl(cyclam)](PF6)2 and 22.3±5.1% in the presence of [Ru(NO)(Hedta)]. The PLGA nanoparticles loaded with trans-[Ru(NO)Cl(cyclam)](PF6)2 and [Ru(NO)(Hedta)] exerted in vitro a reduced activity against melanoma cells when compared to the activity of complex in

  6. Hyaluronic acid-decorated poly(lactic-co-glycolic acid) nanoparticles for combined delivery of docetaxel and tanespimycin.

    PubMed

    Pradhan, Roshan; Ramasamy, Thiruganesh; Choi, Ju Yeon; Kim, Jeong Hwan; Poudel, Bijay Kumar; Tak, Jin Wook; Nukolova, Natalia; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2015-06-05

    Multiple-drug combination therapy is becoming more common in the treatment of advanced cancers because this approach can decrease side effects and delay or prevent drug resistance. In the present study, we developed hyaluronic acid (HA)-decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGA NPs) for co-delivery of docetaxel (DTX) and tanespimycin (17-AAG). DTX and 17-AAG were simultaneously loaded into HA-PLGA NPs using an oil-in-water emulsification/solvent evaporation method. Several formulations were tested. HA-PLGA NPs loaded with DTX and 17-AAG at a molar ratio of 2:1 produced the smallest particle size (173.3±2.2nm), polydispersity index (0.151±0.026), and zeta potential (-12.4±0.4mV). Approximately 60% and 40% of DTX and 17-AAG, respectively, were released over 168h in vitro. Cytotoxicity assays performed in vitro using MCF-7, MDA-MB-231, and SCC-7 cells showed that dual drug-loaded HA-PLGA NPs at a DTX:17-AAG molar ratio of 2:1 exhibited the highest synergistic effect, with combination index values of 0.051, 0.036, and 0.032, respectively, at the median effective dose. Furthermore, synergistic antitumor activity was demonstrated in vivo in a CD44 and RHAMM (CD168) - overexpressing squamous cell carcinoma (SCC-7) xenograft in nude mice. These findings indicated that nanosystem-based co-delivery of DTX and 17-AAG could provide a promising combined therapeutic strategy for enhanced antitumor therapy.

  7. Microneedle-mediated transcutaneous immunization with plasmid DNA coated on cationic PLGA nanoparticles

    PubMed Central

    Kumar, Amit; Wonganan, Piyanuch; Sandoval, Michael A.; Li, Xinran; Zhu, Saijie; Cui, Zhengrong

    2012-01-01

    Previously, it was shown that microneedle-mediated transcutaneous immunization with plasmid DNA can potentially induce a stronger immune response than intramuscular injection of the same plasmid DNA. In the present study, we showed that the immune responses induced by transcutaneous immunization by applying plasmid DNA onto a skin area pretreated with solid microneedles were significantly enhanced by coating the plasmid DNA on the surface of cationic nanoparticles. In addition, the net surface charge of the DNA-coated nanoparticles significantly affected their in vitro skin permeation and their ability to induce immune responses in vivo. Transcutaneous immunization with plasmid DNA-coated net positively charged anoparticles elicited a stronger immune response than with plasmid DNA-coated net negatively charged nanoparticles or by intramuscular immunization with plasmid DNA alone. Transcutaneous immunization with plasmid DNA-coated net positively charged nanoparticles induced comparable immune responses as intramuscular injection of them, but transcutaneous immunization was able to induce specific mucosal immunity and a more balanced T helper type 1 and type 2 response. The ability of the net positively charged DNA-coated nanoparticles to induce a strong immune response through microneedle-mediated transcutaneous immunization may be attributed to their ability to increase the expression of the antigen gene encoded by the plasmid and to more effectively stimulate the maturation of antigen-presenting cells. PMID:22921518

  8. Current strategies in modification of PLGA-based gene delivery system.

    PubMed

    Ramezani, Mohammad; Ebrahimian, Mahboubeh; Hashemi, Maryam

    2016-12-05

    The successful gene therapy has been limited by safe and efficient delivery of nucleic acid to the target cells. Poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are able to deliver drugs and gene efficiently. This formulation has several advantages in comparison with other formulations including improvement of solubility, stability, controlling of degradation and release of the entrapped agents. For application of PLGA as gene carrier, there exist many challenges. PLGA nanoparticles could protect the encapsulated DNA from in vivo degradation but the DNA release is slowl and their negative charge acts as a barrier to DNA incorporation and delivery. Also, during the preparation process, DNA could be exposed to high shear stress and organic solvents which could result in its inactivation. Moreover, PLGA NPs could be modified with different agents to reduce its cytotoxicity, to enhance the delivery efficiency and to target it to specific tissues/cells. This review summarizes different methods used for the preparation of PLGA NPs as gene carriers and recent strategies for modification of PLGA particles applied in gene therapy.

  9. Multifunctional Bi2S3/PLGA nanocapsule for combined HIFU/radiation therapy.

    PubMed

    Yao, Ming-hua; Ma, Ming; Chen, Yu; Jia, Xiao-qing; Xu, Guang; Xu, Hui-xiong; Chen, Hang-rong; Wu, Rong

    2014-09-01

    A multifunctional organic-inorganic hybrid nanocapsule based on Bi2S3-embedded poly (lactic-co-glycolic acid) (PLGA) nanocapsule has been elaborately designed to combine the merits of both polymeric shell structure and Bi2S3 nanoparticles. Hydrophobic Bi2S3 nanoparticles were successfully introduced into the PLGA nanocapsules via a facile and efficient water/oil/water (W/O/W) emulsion strategy. The elastic polymeric PLGA shell provides the excellent capability of ultrasound contrast imaging to the Bi2S3/PLGA. Meanwhile, the potential of these microcapsules to enhance the high intensity focused ultrasound (HIFU) therapy was demonstrated. Importantly, this research provided the first example of both in vitro and in vivo to demonstrate the radiosensitization effect of Bi2S3-embedded PLGA hybrid nanocapsules against prostate cancer under external X-ray irradiation. Thus, the successful integration of the Bi2S3 and PLGA nanocapsules provided an alternative strategy for the highly efficient ultrasound guided HIFU/RT synergistic therapy.

  10. Mechanistic analysis of Zein nanoparticles/PLGA triblock in situ forming implants for glimepiride

    PubMed Central

    Ahmed, Osama Abdelhakim Aly; Zidan, Ahmed Samir; Khayat, Maan

    2016-01-01

    Objectives The study aims at applying pharmaceutical nanotechnology and D-optimal fractional factorial design to screen and optimize the high-risk variables affecting the performance of a complex drug delivery system consisting of glimepiride–Zein nanoparticles and inclusion of the optimized formula with thermoresponsive triblock copolymers in in situ gel. Methods Sixteen nanoparticle formulations were prepared by liquid–liquid phase separation method according to the D-optimal fractional factorial design encompassing five variables at two levels. The responses investigated were glimepiride entrapment capacity (EC), particle size and size distribution, zeta potential, and in vitro drug release from the prepared nanoparticles. Furthermore, the feasibility of embedding the optimized Zein-based glimepiride nanoparticles within thermoresponsive triblock copolymers poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) in in situ gel was evaluated for controlling glimepiride release rate. Results Through the systematic optimization phase, improvement of glimepiride EC of 33.6%, nanoparticle size of 120.9 nm with a skewness value of 0.2, zeta potential of 11.1 mV, and sustained release features of 3.3% and 17.3% drug released after 2 and 24 hours, respectively, were obtained. These desirability functions were obtained at Zein and glimepiride loadings of 50 and 75 mg, respectively, utilizing didodecyldimethylammonium bromide as a stabilizer at 0.1% and 90% ethanol as a common solvent. Moreover, incorporating this optimized formulation in triblock copolymers-based in situ gel demonstrated pseudoplastic behavior with reduction of drug release rate as the concentration of polymer increased. Conclusion This approach to control the release of glimepiride using Zein nanoparticles/triblock copolymers-based in situ gel forming intramuscular implants could be useful for improving diabetes treatment effectiveness. PMID:26893561

  11. Chitosan-PLGA polymer blends as coatings for hydroxyapatite nanoparticles and their effect on antimicrobial properties, osteoconductivity and regeneration of osseous tissues.

    PubMed

    Ignjatović, Nenad; Wu, Victoria; Ajduković, Zorica; Mihajilov-Krstev, Tatjana; Uskoković, Vuk; Uskoković, Dragan

    2016-03-01

    Composite biomaterials comprising nanostructured hydroxyapatite (HAp) have an enormous potential for natural bone tissue reparation, filling and augmentation. Chitosan (Ch) as a naturally derived polymer has many physicochemical and biological properties that make it an attractive material for use in bone tissue engineering. On the other hand, poly-D,L-lactide-co-glycolide (PLGA) is a synthetic polymer with a long history of use in sustained drug delivery and tissue engineering. However, while chitosan can disrupt the cell membrane integrity and may induce blood thrombosis, PLGA releases acidic byproducts that may cause tissue inflammation and interfere with the healing process. One of the strategies to improve the biocompatibility of Ch and PLGA is to combine them with compounds that exhibit complementary properties. In this study we present the synthesis and characterization, as well as in vitro and in vivo analyses of a nanoparticulate form of HAp coated with two different polymeric systems: (a) Ch and (b) a Ch-PLGA polymer blend. Solvent/non-solvent precipitation and freeze-drying were used for synthesis and processing, respectively, whereas thermogravimetry coupled with mass spectrometry was used for phase identification purposes in the coating process. HAp/Ch composite particles exhibited the highest antimicrobial activity against all four microbial strains tested in this work, but after the reconstruction of the bone defect they also caused inflammatory reactions in the newly formed tissue where the defect had lain. Coating HAp with a polymeric blend composed of Ch and PLGA led to a decrease in the reactivity and antimicrobial activity of the composite particles, but also to an increase in the quality of the newly formed bone tissue in the reconstructed defect area.

  12. Synthetic long peptide-based vaccine formulations for induction of cell mediated immunity: A comparative study of cationic liposomes and PLGA nanoparticles.

    PubMed

    Varypataki, Eleni Maria; Silva, Ana Luisa; Barnier-Quer, Christophe; Collin, Nicolas; Ossendorp, Ferry; Jiskoot, Wim

    2016-03-28

    Nanoparticulate formulations for synthetic long peptide (SLP)-cancer vaccines as alternative to clinically used Montanide ISA 51- and squalene-based emulsions are investigated in this study. SLPs were loaded into TLR ligand-adjuvanted cationic liposomes and PLGA nanoparticles (NPs) to potentially induce cell-mediated immune responses. The liposomal and PLGA NP formulations were successfully loaded with up to four different compounds and were able to enhance antigen uptake by dendritic cells (DCs) and subsequent activation of T cells in vitro. Subcutaneous vaccination of mice with the different formulations showed that the SLP-loaded cationic liposomes were the most efficient for the induction of functional antigen-T cells in vivo, followed by PLGA NPs which were as potent as or even more than the Montanide and squalene emulsions. Moreover, after transfer of antigen-specific target cells in immunized mice, liposomes induced the highest in vivo killing capacity. These findings, considering also the inadequate safety profile of the currently clinically used adjuvant Montanide ISA-51, make these two particulate, biodegradable delivery systems promising candidates as delivery platforms for SLP-based immunotherapy of cancer.

  13. Particulate Systems Based on Poly(Lactic-co-Glycolic)Acid (pLGA) for Immunotherapy of Cancer.

    PubMed

    Rahimian, Sima; Fransen, Marieke F; Kleinovink, Jan Willem; Amidi, Maryam; Ossendorp, Ferry; Hennink, Wim E

    2015-01-01

    Immunotherapy of cancer is a promising therapeutic approach which aims to eliminate malignancies by inducing or enhancing an immune response against the tumor. Immunotherapy, however, faces several challenges such as local immunosuppression in the tumor area leading to immunological tolerance. To overcome these challenges, particulate formulations such as nano- and microparticles containing immunotherapeutics have been developed to increase therapeutic efficacy and reduce toxicity of immunotherapy. Particulate formulations based on biodegradable aliphatic polyesters such as poly(lactic-co-glycolic acid) (pLGA) have been extensively used with promising results. In this review, we addressed the potential of pLGA-based particulate formulations for immunotherapy of cancer. The discussion was focused on cancer vaccines and delivery of immunomodulatory antibodies. Features and drawbacks of pLGA systems were discussed together with several examples of recently developed therapeutic cancer vaccines and antibody-loaded particulate systems. Various strategies to overcome the drawbacks and optimize the formulations were given. In conclusion, pLGA-based particulate systems are attractive carriers for development of clinically acceptable formulations in immunotherapy of cancer.

  14. Ultrasound-Mediated Microbubble Destruction (UMMD) Facilitates the Delivery of CA19-9 Targeted and Paclitaxel Loaded mPEG-PLGA-PLL Nanoparticles in Pancreatic Cancer

    PubMed Central

    Xing, Lingxi; Shi, Qiusheng; Zheng, Kailiang; Shen, Ming; Ma, Jing; Li, Fan; Liu, Yang; Lin, Lizhou; Tu, Wenzhi; Duan, Yourong; Du, Lianfang

    2016-01-01

    Pancreatic cancer, one of the most lethal human malignancies with dismal prognosis, is refractory to existing radio-chemotherapeutic treatment modalities. There is a critical unmet need to develop effective approaches, especially for targeted pancreatic cancer drug delivery. Targeted and drug-loaded nanoparticles (NPs) combined with ultrasound-mediated microbubble destruction (UMMD) have been shown to significantly increase the cellular uptake in vitro and drug retention in vivo, suggesting a promising strategy for cancer therapy. In this study, we synthesized pancreatic cancer-targeting organic NPs that were modified with anti CA19-9 antibody and encapsulated paclitaxol (PTX). The three-block copolymer methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) constituted the skeleton of the NPs. We speculated that the PTX-NPs-anti CA19-9 would circulate long-term in vivo, "actively target" pancreatic cancer cells, and sustainably release the loaded PTX while UMMD would "passively target" the irradiated tumor and effectively increase the permeability of cell membrane and capillary gaps. Our results demonstrated that the combination of PTX-NPs-anti CA19-9 with UMMD achieved a low IC50, significant cell cycle arrest, and cell apoptosis in vitro. In mouse pancreatic tumor xenografts, the combined application of PTX-NP-anti CA19-9 NPs with UMMD attained the highest tumor inhibition rate, promoted the pharmacokinetic profile by increasing AUC, t1/2, and mean residence time (MRT), and decreased clearance. Consequently, the survival of the tumor-bearing nude mice was prolonged without obvious toxicity. The dynamic change in cellular uptake, targeted real-time imaging, and the concentration of PTX in the plasma and tumor were all closely associated with the treatment efficacy both in vitro and in vivo. Our study suggests that PTX-NP-anti CA19-9 NPs combined with UMMD is a promising strategy for the treatment of pancreatic cancer. PMID:27446491

  15. Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment

    PubMed Central

    Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Liu, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

    2016-01-01

    Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD. PMID:27994458

  16. Kanamycin Sulphate Loaded PLGA-Vitamin-E-TPGS Long Circulating Nanoparticles Using Combined Coating of PEG and Water-Soluble Chitosan

    PubMed Central

    Mustafa, Sanaul

    2017-01-01

    Kanamycin sulphate (KS) is a Mycobacterium tuberculosis protein synthesis inhibitor. Due to its intense hydrophilicity, KS is cleared from the body within 8 h. KS has a very short plasma half-life (2.5 h). KS is used in high concentrations to reach the therapeutic levels in plasma, which results in serious nephrotoxicity/ototoxicity. To overcome aforementioned limitations, the current study aimed to develop KS loaded PLGA-Vitamin-E-TPGS nanoparticles (KS-PLGA-TPGS NPs), to act as an efficient carrier for controlled delivery of KS. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG) to KS-PLGA-TPGS NPs and adsorption of water-soluble chitosan (WSC) (cationic deacetylated chitin) to particle surface, was raised for surface modification of NPs. Surface modified NPs (KS-PEG-WSC NPs) were prepared to provide controlled delivery and circulate in the bloodstream for an extended period of time, thus minimizing dosing frequency. In vivo pharmacokinetics and in vivo biodistribution following intramuscular administration were investigated. NPs surface charge was close to neutral +3.61 mV and significantly affected by the WSC coating. KS-PEG-WSC NPs presented striking prolongation in blood circulation, reduced protein binding, and long drew-out the blood circulation half-life with resultant reduced kidney sequestration vis-à-vis KS-PLGA-TPGS NPs. The studies, therefore, indicate the successful formulation development of KS-PEG-WSC NPs with reduced frequency of dosing of KS indicating low incidence of nephrotoxicity/ototoxicity. PMID:28352475

  17. Microspheres prepared with different co-polymers of poly(lactic-glycolic acid) (PLGA) or with chitosan cause distinct effects on macrophages.

    PubMed

    Bitencourt, Claudia da Silva; Silva, Letícia Bueno da; Pereira, Priscilla Aparecida Tartari; Gelfuso, Guilherme Martins; Faccioli, Lúcia Helena

    2015-12-01

    Microencapsulation of bioactive molecules for modulating the immune response during infectious or inflammatory events is a promising approach, since microspheres (MS) protect these labile biomolecules against fast degradation, prolong the delivery over longer periods of time and, in many situations, target their delivery to site of action, avoiding toxic side effects. Little is known, however, about the influence of different polymers used to prepare MS on macrophages. This paper aims to address this issue by evaluating in vitro cytotoxicity, phagocytosis profile and cytokines release from alveolar macrophages (J-774.1) treated with MS prepared with chitosan, and four different co-polymers of PLGA [poly (lactic-co-glycolic acid)]. The five MS prepared presented similar diameter and zeta potential each other. Chitosan-MS showed to be cytotoxic to J-774.1 cells, in contrast to PLGA-MS, which were all innocuous to this cell linage. PLGA 5000-MS was more efficiently phagocytized by macrophages compared to the other MS tested. PLGA 5000-MS and 5002-MS induced significant production of TNF-α, while 5000-MS, 5004-MS and 7502-MS decreased spontaneous IL-6 release. Nevertheless, only PLGA 5002-MS induced significant NFkB/SEAP activation. These findings together show that MS prepared with distinct PLGA co-polymers are differently recognized by macrophages, depending on proportion of lactic and glycolic acid in polymeric chain, and on molecular weight of the co-polymer used. Selection of the most adequate polymer to prepare a microparticulate drug delivery system to modulate immunologic system may take into account, therefore, which kind of immunomodulatory response is more adequate for the required treatment.

  18. pH-sensitive nanoparticles of poly(L-histidine)-poly(lactide-co-glycolide)-tocopheryl polyethylene glycol succinate for anti-tumor drug delivery.

    PubMed

    Li, Zhen; Qiu, Lipeng; Chen, Qing; Hao, Tangna; Qiao, Mingxi; Zhao, Haixia; Zhang, Jie; Hu, Haiyang; Zhao, Xiuli; Chen, Dawei; Mei, Lin

    2015-01-01

    A novel pH-sensitive polymer, poly(L-histidine)-poly(lactide-co-glycolide)-tocopheryl polyethylene glycol succinate (PLH-PLGA-TPGS), was synthesized to design a biocompatible drug delivery system for cancer chemotherapy. The structure of the PLH-PLGA-TPGS copolymer was confirmed by (1)H-NMR, FTIR and GPC. The apparent pKa of the PLH-PLGA-TPGS copolymer was calculated to be 6.33 according to the acid-base titration curve. The doxorubicin (DOX)-loaded nanoparticles (PLH-PLGA-TPGS nanoparticles and PLGA-TPGS nanoparticles) and corresponding blank nanoparticles were prepared by a co-solvent evaporation method. The blank PLH-PLGA-TPGS nanoparticles showed an acidic pH-induced increase in particle size. The DOX-loaded nanoparticles based on PLH-PLGA-TPGS showed a pH-triggered drug-release behavior under acidic conditions. The results of in vitro cytotoxicity experiment on MCF-7 and MCF-7/ADR cells showed that the DOX-loaded PLH-PLGA-TPGS nanoparticles resulted in lower cell viability versus the PLGA-TPGS nanoparticles and free DOX solution. Confocal laser scanning microscopy images showed that DOX-loaded PLH-PLGA-TPGS nanoparticles were internalized by MCF-7/ADR cells after 1 and 4h incubation and most of them accumulated in lysosomes to accelerate DOX release under acidic conditions. In summary, the PLH-PLGA-TPGS nanoparticles have great potential to be used as carriers for anti-tumor drug delivery.

  19. Synthesis and evaluation of airway targeted PLGA nanoparticles for drug delivery in obstructive lung diseases.

    PubMed

    Vij, Neeraj

    2012-01-01

    Chronic airway inflammation is a hallmark of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease), and CF (cystic fibrosis). It is also a major challenge in delivery and therapeutic efficacy of nano-based delivery systems in these chronic airway conditions as nanoparticle (NP) need to bypass airways defense mechanisms as we recently discussed. NPs which are capable of overcoming airways defense mechanisms should allow targeted drug delivery to disease cells. Over the last decade there has been increasing interest in development of targeted NPs for cancer but relatively little effort on designing novel systems for treating chronic inflammatory and obstructive airway conditions. Here we describe methods for preparing drug loaded multifunctional nanoparticles for targeted delivery to specific cell types in airways. The formulations and methods for selective drug delivery, discussed here are currently under preclinical development in our laboratory for treating chronic airway conditions such as COPD, CF, and asthma.

  20. Stability of fluorescent labels in PLGA polymeric nanoparticles: Quantum dots versus organic dyes.

    PubMed

    Abdel-Mottaleb, Mona M A; Beduneau, Arnaud; Pellequer, Yann; Lamprecht, Alf

    2015-10-15

    Polymeric nanoparticles (NPs) are currently being investigated for various therapeutic, diagnostic and drug delivery applications. The study of their interactions and fate in biological systems is frequently performed via their fluorescent labeling and following them using fluorescent microscopy. Quantum dots are proposed as stable fluorescent label and compared to other organic dyes (Nile red and DiI) in terms of their entrapment, diffusion in different aqueous or lipophilic media and photostability. In vitro transfer to hydrophilic PBS solution showed that after 8h, 4.2±2.2, 15.5±2.0 and 0.9±0.02% was released from the QDs, NR and DiI nanoparticles, respectively. However, higher diffusion rates were observed in the lipophilic medium chain triglyceride and artificial sebum for all the dyes used. Fluorescent intensity of the three different markers was found to be stable over a period of 24h. Continuous illumination with laser beam using a confocal laser scanning microscopy indicated the superior stability of quantum dots compared to the other organic dyes. Skin permeation experiments have shown that QDs were the most representative marker for the polymeric nanoparticles skin penetration.

  1. Attenuation of experimental autoimmune neuritis with locally administered lovastatin-encapsulating poly(lactic-co-glycolic) acid nanoparticles.

    PubMed

    Langert, Kelly A; Goshu, Bruktawit; Stubbs, Evan B

    2017-01-01

    Acute inflammatory demyelinating polyneuropathy (AIDP) is an aggressive antibody- and T-cell-mediated variant of Guillain-Barré Syndrome (GBS), a prominent and debilitating autoimmune disorder of the peripheral nervous system. Despite advancements in clinical management, treatment of patients with AIDP/GBS and its chronic variant CIDP remains palliative and relies on the use of non-specific immunemodulating therapies. Our laboratory has previously reported that therapeutic administration of statins safely attenuates the clinical severity of experimental autoimmune neuritis (EAN), a well-characterized animal model of AIDP/GBS, by restricting the migration of autoreactive leukocytes across peripheral nerve microvascular endoneurial endothelial cells that form the blood-nerve barrier. Despite these advancements, the clinical application of systemically administered statins for the management of inflammatory disorders remains controversial as a result of disappointingly inconclusive phase trials. Here, poly(lactic-co-glycolic) acid (PLGA) nanoparticles were evaluated as an alternative strategy by which to locally administer statins for the management of EAN. When tested in vitro, lovastatin-encapsulating PLGA nanoparticles elicited a marked increase in RhoB mRNA content in peripheral nerve microvascular endoneurial endothelial cells, similar to cells treated with activated unencapsulated lovastatin. Unilateral peri-neural administration of lovastatin-encapsulating PLGA nanoparticles, but not empty nanoparticles, to naïve Lewis rats similarly enhanced RhoB mRNA content in adjacent nerve and muscle tissue. When administered in this manner, serum levels of lovastatin were below the level of detection. Bilateral peri-neural administration of lovastatin-encapsulating PLGA nanoparticles to EAN-induced Lewis rats significantly attenuated EAN clinical severity while protecting against EAN-induced peripheral nerve morphological and functional deficits. This study provides

  2. Dendrimer, liposomes, carbon nanotubes and PLGA nanoparticles: one platform assessment of drug delivery potential.

    PubMed

    Mody, Nishi; Tekade, Rakesh Kumar; Mehra, Neelesh Kumar; Chopdey, Prashant; Jain, Narendra Kumar

    2014-04-01

    Liposomes (LIP), nanoparticles (NP), dendrimers (DEN), and carbon nanotubes (CNTs), represent eminent classes of drug delivery devices. A study was carried out herewith by employing docetaxel (DTX) as model drug to assess their comparative drug delivery potentials. Under optimized conditions, highest entrapment of DTX was observed in CNT-based formulation (DTX-CNTs, 74.70 ± 4.9%) followed by nanoparticles (DTX-NP, 62.34 ± 1.5%), liposome (49.2 ± 1.51%), and dendrimers (28.26 ± 1.74%). All the formulations were found to be of nanometric size. In vitro release studies were carried out in PBS (pH 7.0 and 4.0), wherein all the formulations showed biphasic release pattern. Cytotoxicity assay in human cervical cancer SiHa cells inferred lowest IC50 value of 1,235.09 ± 41.93 nM with DTX-CNTs, followed by DTX-DEN, DTX-LIP, DTX-NP with IC50 values of 1,571.22 ± 151.27, 1,653.98 ± 72.89, 1,922.75 ± 75.15 nM, respectively. Plain DTX showed higher hemolytic toxicity of 22.48 ± 0.94%, however loading of DTX inside nanocarriers drastically reduced its hemolytic toxicity (DTX-DEN, 17.22 ± 0.48%; DTX-LIP, 4.13 ± 0.19%; DTX-NP, 6.43 ± 0.44%; DTX-CNTs, 14.87 ± 1.69%).

  3. Antimicrobial activity of a new synthetic peptide loaded in polylactic acid or poly(lactic-co-glycolic) acid nanoparticles against Pseudomonas aeruginosa, Escherichia coli O157:H7 and methicillin resistant Staphylococcus aureus (MRSA).

    PubMed

    Cruz, J; Flórez, J; Torres, R; Urquiza, M; Gutiérrez, J A; Guzmán, F; Ortiz, C C

    2017-03-01

    Nanocarrier systems are currently being developed for peptide, protein and gene delivery to protect them in the blood circulation and in the gastrointestinal tract. Polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with a new antimicrobial GIBIM-P5S9K peptide were obtained by the double emulsion solvent extraction/evaporation method. PLA- and PLGA-NPs were spherical with sizes between 300 and 400 nm for PLA and 200 and 300 nm for PLGA and <0.3 polydispersity index as determined by dynamic light scattering and scanning electron microscopy), having the zeta potential of >20 mV. The peptide-loading efficiency of PLA-NP and PLGA-NPs was 75% and 55%, respectively. PLA- and PLGA-NPs released around 50% of this peptide over 8 h. In 10% human sera the size of peptide loaded PLA- and PLGA-NPs increased between 25.2% and 39.3%, the PDI changed from 3.2 to 5.1 and the surface charge from -7.15 to 14.6 mV. Both peptide loaded PLA- and PLGA-NPs at 0.5 μM peptide concentration inhibited the growth of Escherichia coli O157:H7 (E. coli O157:H7), methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. aeruginosa (P. aeruginosa). In contrast, free peptide inhibited at 10 μM but did not inhibit at 0.5 and 1 μM. These PLA- and PLGA-NPs presented <10% hemolysis indicating that they are hemocompatible and promising for delivery and protection system of GIBIM-P5S9K peptide.

  4. Antimicrobial activity of a new synthetic peptide loaded in polylactic acid or poly(lactic-co-glycolic) acid nanoparticles against Pseudomonas aeruginosa, Escherichia coli O157:H7 and methicillin resistant Staphylococcus aureus (MRSA)

    NASA Astrophysics Data System (ADS)

    Cruz, J.; Flórez, J.; Torres, R.; Urquiza, M.; Gutiérrez, J. A.; Guzmán, F.; Ortiz, C. C.

    2017-03-01

    Nanocarrier systems are currently being developed for peptide, protein and gene delivery to protect them in the blood circulation and in the gastrointestinal tract. Polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with a new antimicrobial GIBIM-P5S9K peptide were obtained by the double emulsion solvent extraction/evaporation method. PLA- and PLGA-NPs were spherical with sizes between 300 and 400 nm for PLA and 200 and 300 nm for PLGA and <0.3 polydispersity index as determined by dynamic light scattering and scanning electron microscopy), having the zeta potential of >20 mV. The peptide-loading efficiency of PLA-NP and PLGA-NPs was 75% and 55%, respectively. PLA- and PLGA-NPs released around 50% of this peptide over 8 h. In 10% human sera the size of peptide loaded PLA- and PLGA-NPs increased between 25.2% and 39.3%, the PDI changed from 3.2 to 5.1 and the surface charge from ‑7.15 to 14.6 mV. Both peptide loaded PLA- and PLGA-NPs at 0.5 μM peptide concentration inhibited the growth of Escherichia coli O157:H7 (E. coli O157:H7), methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. aeruginosa (P. aeruginosa). In contrast, free peptide inhibited at 10 μM but did not inhibit at 0.5 and 1 μM. These PLA- and PLGA-NPs presented <10% hemolysis indicating that they are hemocompatible and promising for delivery and protection system of GIBIM-P5S9K peptide.

  5. Evaluation of intra-articular delivery of hyaluronic acid functionalized biopolymeric nanoparticles in healthy rat knees.

    PubMed

    Zille, Hervé; Paquet, Joseph; Henrionnet, Christel; Scala-Bertola, Julien; Leonard, Michèle; Six, Jean Luc; Deschamp, Frantz; Netter, Patrick; Vergès, José; Gillet, Pierre; Grossin, Laurent

    2010-01-01

    The aim of this study is to evaluate the toxicity of nanoparticles of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co-glycolic acid) (PLGA) covered by chemically esterified amphiphilic hyaluronate (HA) which will be used for intra-articular injection as a drug carrier for the treatment of arthritis (RA) and/or osteoarthritis (OA). PLA and PLGA are FDA approved polymers that are already used for the preparation of nano or microparticles. HA is a natural polysaccharide already present in the articulations known to interact with the CD44 receptors of the cells (especially chondrocytes). Therefore, we can envisage that the HA covering can improve the interactions between the cells and the nanoparticles, leading to better targeting or biodistribution. The knee of healthy male rats was injected one to two times weekly, with various concentrations of nanoparticles encapsulating Dextran-FITC. The synovial membranes and the patellae were collected aseptically and histologically analyzed to assess the effects and localization of the nanocapsules in the knee joint. We did not observe significant modifications in the synovial membranes (weak hyperplasia) or patellae integrity after local administration of nanodevices into the rats. While we found some nanoparticles in the synovial membrane, none were detected in the patellae. Moreover, the histological observations for patellae were confirmed by radiosulfate intake, which depicted no decrease in proteoglycans biosynthesis in nanoparticles treated animals. Concerning the safety towards synovial membranes, we also had a look at the inflammatory response after injections of nanoparticles covered by amphiphilic HA or polyvinyl alcohol (PVA) by monitoring the mRNA expression levels of some specific early cytokines (IL-1β and TNF-α). Once again, no differences were observed between the control rats and the rats treated with nanoparticles. Considering these preliminary results obtained in healthy rats, we can establish that

  6. Poly[lactic-co-(glycolic acid)]-grafted hyaluronic acid copolymer micelle nanoparticles for target-specific delivery of doxorubicin.

    PubMed

    Lee, Hyukjin; Ahn, Cheol-Hee; Park, Tae Gwan

    2009-04-08

    PLGA-grafted HA copolymers were synthesized and utilized as target specific micelle carriers for DOX. For grafting hydrophobic PLGA chains onto the backbone of hydrophilic HA, HA was solubilized in an anhydrous DMSO by nano-complexing with dimethoxy-PEG. The carboxylic groups of HA were chemically grafted with PLGA, producing HA-g-PLGA copolymers. Resultant HA-g-PLGA self-assembled in aqueous solution to form multi-cored micellar aggregates and DOX was encapsulated during the self-assembly. DOX-loaded HA-g-PLGA micelle nanoparticles exhibited higher cellular uptake and greater cytotoxicity than free DOX for HCT-116 cells that over-expressed HA receptor, suggesting that they were taken up by the cells via HA receptor-mediated endocytosis.

  7. Prolonged gene silencing by siRNA/chitosan-g-deoxycholic acid polyplexes loaded within biodegradable polymer nanoparticles.

    PubMed

    Lee, Jeong Yu; Lee, Soo Hyeon; Oh, Mi Hwa; Kim, Jee Seon; Park, Tae Gwan; Nam, Yoon Sung

    2012-09-10

    Recently, small interfering RNA (siRNA) has received much attention for therapeutic applications; however, low transfection efficiency and intrinsic instability limit effective gene silencing. Here we show a new approach based on the incorporation of siRNA/polyelectrolyte complexes into biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles to stabilize siRNA within a hydrophobic solid matrix for prolonged gene silencing. To solubilize siRNA in organic media, chitosan oligosaccharides grafted with deoxycholic acids are synthesized and complexed with siRNA, generating a self-assembled polyelectrolyte complex of 123.9 ± 56.8 nm in diameter. The complex is mixed with PLGA solution and emulsified in water to prepare siRNA-loaded PLGA nanoparticles having a diameter of about 230 nm. The excellent structural stability of the prepared nanoparticles leads to efficient cellular uptake followed by effective gene silencing even in the presence of serum proteins. These results suggest that the encapsulation of siRNA into biodegradable polymer matrix can be an effective means of improving the structural stability of siRNA for prolonged therapeutic efficacy.

  8. PLGA Nanoparticles Loaded Cerebrolysin: Studies on Their Preparation and Investigation of the Effect of Storage and Serum Stability with Reference to Traumatic Brain Injury.

    PubMed

    Ruozi, Barbara; Belletti, Daniela; Sharma, Hari S; Sharma, Aruna; Muresanu, Dafin F; Mössler, Herbert; Forni, Flavio; Vandelli, Maria Angela; Tosi, Giovanni

    2015-10-01

    Cerebrolysin is a peptide mixture able to ameliorate symptomatology and delay progression of neurological disorders such as Alzheimer's disease and dementia. The administration of this drug in humans presents several criticisms due to its short half-life, poor stability, and high doses needed to achieve the effect. This paper investigates the potential of polylactic-co-glycolide (PLGA) nanoparticles (NPs) as sustained release systems for iv administration of cerebrolysin in normal and brain injured rats. NPs were prepared by water-in-oil-in-water (w/o/w) double emulsion technique and characterized by light scattering for mean size and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The NPs produced by double sonication under cooling at 60 W for 45 s, 12 mL of 1 % w:v of PVA, and 1:0.6 w:w drug/PLGA ratio (C-NPs4) displayed an adequate loading of drug (24 ± 1 mg/100 mg of NPs), zeta potential value (-13 mV), and average diameters (ranged from 250 to 330 nm) suitable to iv administration. SEM images suggested that cerebrolysin was molecularly dispersed into matricial systems and partially adhered to the NP surface. A biphasic release with an initial burst effect followed by sustained release over 24 h was observed. Long-term stability both at room and at low temperature of freeze-dried NPs was investigated. To gain deeper insight into NP stability after in vivo administration, the stability of the best NP formulation was also tested in serum. These PLGA NPs loaded with cerebrolysin were able to reduce brain pathology following traumatic brain injury. However, the size, the polydispersivity, and the surface properties of sample were significantly affected by the incubation time and the serum concentration.

  9. Bioerodable PLGA-Based Microparticles for Producing Sustained-Release Drug Formulations and Strategies for Improving Drug Loading

    PubMed Central

    Han, Felicity Y.; Thurecht, Kristofer J.; Whittaker, Andrew K.; Smith, Maree T.

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) is the most widely used biomaterial for microencapsulation and prolonged delivery of therapeutic drugs, proteins and antigens. PLGA has excellent biodegradability and biocompatibility and is generally recognized as safe by international regulatory agencies including the United States Food and Drug Administration and the European Medicines Agency. The physicochemical properties of PLGA may be varied systematically by changing the ratio of lactic acid to glycolic acid. This in turn alters the release rate of microencapsulated therapeutic molecules from PLGA microparticle formulations. The obstacles hindering more widespread use of PLGA for producing sustained-release formulations for clinical use include low drug loading, particularly of hydrophilic small molecules, high initial burst release and/or poor formulation stability. In this review, we address strategies aimed at overcoming these challenges. These include use of low-temperature double-emulsion methods to increase drug-loading by producing PLGA particles with a small volume for the inner water phase and a suitable pH of the external phase. Newer strategies for producing PLGA particles with high drug loading and the desired sustained-release profiles include fabrication of multi-layered microparticles, nanoparticles-in-microparticles, use of hydrogel templates, as well as coaxial electrospray, microfluidics, and supercritical carbon dioxide methods. Another recent strategy with promise for producing particles with well-controlled and reproducible sustained-release profiles involves complexation of PLGA with additives such as polyethylene glycol, poly(ortho esters), chitosan, alginate, caffeic acid, hyaluronic acid, and silicon dioxide. PMID:27445821

  10. Novel lansoprazole-loaded nanoparticles for the treatment of gastric acid secretion-related ulcers: in vitro and in vivo pharmacokinetic pharmacodynamic evaluation.

    PubMed

    Alai, Milind; Lin, Wen Jen

    2014-05-01

    The objective of this study is to combine nanoparticle design and enteric coating technique to sustain the delivery of an acid-labile drug, lansoprazole (LPZ), in the treatment of acid reflux disorders. Lansoprazole-loaded Eudragit® RS100 nanoparticles (ERSNP-LPZ) as well as poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGANP-LPZ) were prepared using a solvent evaporation/extraction method. The effects of nanoparticle charge and permeation enhancers on lansoprazole uptake was assessed in Caco-2 cells. The confocal microscopic images revealed the successful localization of nanoparticles in the cytoplasm of Caco-2 cells. The cellular uptake of positively charged Eudragit nanoparticles was significantly higher than that of negatively charged PLGA nanoparticles, which were enhanced by sodium caprate via the transcellular pathway. Both types of nanoparticles exhibited sustained drug release behavior in vitro. The oral administration of enteric-coated capsules filled with nanoparticles sustained and prolonged the LPZ concentration up to 24 h in ulcer-induced Wistar rats, and 92.4% and 89.2% of gastric ulcers healed after a 7-day treatment with either EC-ERSNP1010-Na caprate or EC-PLGANP1005-Na caprate, respectively.

  11. Alpha-tocopheryl polyethylene glycol succinate-emulsified poly(lactic-co-glycolic acid) nanoparticles for reversal of multidrug resistance in vitro

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Guo, Miao; Lu, Yu; Ding, Li-Ying; Ron, Wen-Ting; Liu, Ya-Qing; Song, Fei-Fei; Yu, Shu-Qin

    2012-12-01

    Multidrug resistance (MDR) is one of the factors in the failure of anticancer chemotherapy. In order to enhance the anticancer effect of P-glycoprotein (P-gp) substrates, inhibition of the P-gp efflux pump on MDR cells is a good tactic. We designed novel multifunctional drug-loaded alpha-tocopheryl polyethylene glycol succinate (TPGS)/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPGS/PLGA/SN-38 NPs; SN-38 is 7-ethyl-10-hydroxy-camptothecin), with TPGS-emulsified PLGA NPs as the carrier and modulator of the P-gp efflux pump and SN-38 as the model drug. TPGS/PLGA/SN-38 NPs were prepared using a modified solvent extraction/evaporation method. Physicochemical characterizations of TPGS/PLGA/SN-38 NPs were in conformity with the principle of nano-drug delivery systems (nDDSs), including a diameter of about 200 nm, excellent spherical particles with a smooth surface, narrow size distribution, appropriate surface charge, and successful drug-loading into the NPs. The cytotoxicity of TPGS/PLGA/SN-38 NPs to MDR cells was increased by 3.56 times compared with that of free SN-38. Based on an intracellular accumulation study relative to the time-dependent uptake and efflux inhibition, we suggest novel mechanisms of MDR reversal of TPGS/PLGA NPs. Firstly, TPGS/PLGA/SN-38 NPs improved the uptake of the loaded drug by clathrin-mediated endocytosis in the form of unbroken NPs. Simultaneously, intracellular NPs escaped the recognition of P-gp by MDR cells. After SN-38 was released from TPGS/PLGA/SN-38 NPs in MDR cells, TPGS or/and PLGA may modulate the efflux microenvironment of the P-gp pump, such as mitochondria and the P-gp domain with an ATP-binding site. Finally, the controlled-release drug entered the nucleus of the MDR cell to induce cytotoxicity. The present study showed that TPGS-emulsified PLGA NPs could be functional carriers in nDDS for anticancer drugs that are also P-gp substrates. More importantly, to enhance the therapeutic effect of P-gp substrates, this work

  12. Porous nano-hydroxyapatite/collagen scaffold containing drug-loaded ADM-PLGA microspheres for bone cancer treatment.

    PubMed

    Rong, Zi-Jie; Yang, Lian-Jun; Cai, Bao-Ta; Zhu, Li-Xin; Cao, Yan-Lin; Wu, Guo-Feng; Zhang, Zan-Jie

    2016-05-01

    To develop adriamycin (ADM)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a porous nano-hydroxyapatite/collagen scaffold (ADM-PLGA-NHAC). To provide novel strategies for future treatment of osteosarcoma, the properties of the scaffold, including its in vitro extended-release properties, the inhibition effects of ADM-PLGA-NHAC on the osteosarcoma MG63 cells, and its bone repair capacity, were investigated in vivo and in vitro. The PLGA copolymer was utilized as a drug carrier to deliver ADM-PLGA nanoparticles (ADM-PLGA-NP). Porous nano-hydroxyapatite and collagen were used to materials to produce the porous nano-hydroxyapatite/collagen scaffold (NHAC), into which the ADM-PLGA-NP was loaded. The performance of the drug-carrying scaffold was assessed using multiple techniques, including scanning electron microscopy and in vitro extended release. The antineoplastic activities of scaffold extracts on the human osteosarcoma MG63 cell line were evaluated in vitro using the cell counting kit-8 (CCK8) method and live-dead cell staining. The bone repair ability of the scaffold was assessed based on the establishment of a femoral condyle defect model in rabbits. ADM-PLGA-NHAC and NHAC were implanted into the rat muscle bag for immune response experiments. A tumor-bearing nude mice model was created, and the TUNEL and HE staining results were observed under optical microscopy to evaluate the antineoplastic activity and toxic side effects of the scaffold. The composite scaffold demonstrated extraordinary extended-release properties, and its extracts also exhibited significant inhibition of the growth of osteosarcoma MG63 cells. In the bone repair experiment, no significant difference was observed between ADM-PLGA-NHAC and NHAC by itself. In the immune response experiments, ADM-PLGA-NHAC exhibited remarkable biocompatibility. The in vivo antitumor experiment revealed that the implantation of ADM-PLGA-NHAC in the tumor resulted in a improved antineoplastic

  13. Controlled-release of tetracycline and lovastatin by poly(d,l-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs

    PubMed Central

    Lee, Bor-Shiunn; Lee, Chien-Chen; Wang, Yi-Ping; Chen, Hsiao-Jan; Lai, Chern-Hsiung; Hsieh, Wan-Ling; Chen, Yi-Wen

    2016-01-01

    Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(d,l-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy. PMID:26848264

  14. Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co-glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs.

    PubMed

    Lee, Bor-Shiunn; Lee, Chien-Chen; Wang, Yi-Ping; Chen, Hsiao-Jan; Lai, Chern-Hsiung; Hsieh, Wan-Ling; Chen, Yi-Wen

    2016-01-01

    Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy.

  15. In-vitro anticancer and antimicrobial activities of PLGA/silver nanofiber composites prepared by electrospinning.

    PubMed

    Almajhdi, Fahad N; Fouad, H; Khalil, Khalil Abdelrazek; Awad, Hanem M; Mohamed, Sahar H S; Elsarnagawy, T; Albarrag, Ahmed M; Al-Jassir, Fawzi F; Abdo, Hany S

    2014-04-01

    In the present work, a series of 0, 1 and 7 wt% silver nano-particles (Ag NPs) incorporated poly lactic-co-glycolic acid (PLGA) nano-fibers were synthesized by the electrospinning process. The PLGA/Ag nano-fibers sheets were characterized using SEM, TEM and DSC analyses. The three synthesized PLGA/silver nano-fiber composites were screened for anticancer activity against liver cancer cell line using MTT and LDH assays. The anticancer activity of PLGA nano-fibers showed a remarkable improvement due to increasing the concentration of the Ag NPs. In addition to the given result, PLGA nano-fibers did not show any cytotoxic effect. However, PLGA nano-fibers that contain 1 % nano silver showed anticancer activity of 8.8 %, through increasing the concentration of the nano silver to 7 % onto PLGA nano-fibers, the anticancer activity was enhanced to a 67.6 %. Furthermore, the antibacterial activities of these three nano-fibers, against the five bacteria strains namely; E.coli o157:H7 ATCC 51659, Staphylococcus aureus ATCC 13565, Bacillus cereus EMCC 1080, Listeria monocytogenes EMCC 1875 and Salmonella typhimurium ATCC25566 using the disc diffusion method, were evaluated. Sample with an enhanced inhibitory effect was PLGA/Ag NPs (7 %) which inhibited all strains (inhibition zone diameter 10 mm); PLGA/Ag NPs (1 %) sample inhibited only one strain (B. cereus) with zone diameter 8 mm. The PLGA nano-fiber sample has not shown any antimicrobial activity. Based on the anticancer as well as the antimicrobial results in this study, it can be postulated that: PLGA nanofibers containing 7 % nano silver are suitable as anticancer- and antibiotic-drug delivery systems, as they will increase the anticancer as well as the antibiotic drug potency without cytotoxicity effect on the normal cells. These findings also suggest that Ag NPs, of the size (5-10 nm) evaluated in the present study, are appropriate for therapeutic application from a safety standpoint.

  16. Aggrecan- and COMP-loaded poly-(lactic-co-glycolic acid) nanoparticles stimulate chondrogenic differentiation of human mesenchymal stem cells.

    PubMed

    Jeon, Su Yeon; Park, Ji Sun; Yang, Han Na; Woo, Dae Gyun; Park, Keun-Hong

    2014-02-01

    During embryogenesis, specific proteins expressed in cells have key roles in the formation of differentiated cells and tissues. Delivery of specific proteins into specific cells, both in vitro and in vivo, has proved to be exceedingly difficult. In this study, we developed a safe and efficient protein delivery system using encapsulation of proteins into biodegradable poly-(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). The PLGA NPs were used to deliver proteins into human mesenchymal stem cells (hMSCs). Fluorescent markers loaded into the PLGA NPs were used to verify the internalization of NPs into hMSCs using FACS analysis and confocal microscopy. With these methods, we demonstrated that the encapsulated model proteins are readily delivered into hMSCs, released from the NP vehicles, and, finally, moved into the cytosols. Using chondrogenesis-related proteins such as aggrecan and cartilage oligomeric matrix protein (COMP), chondrogenic differentiation of hMSCs treated with aggrecan and COMP encapsulated PLGA NPs was clearly observed and caused to differentiate into chondrocytes.

  17. Synthesis and characterization of poly(lactic-co-glycolic) acid nanoparticles-loaded chitosan/bioactive glass scaffolds as a localized delivery system in the bone defects.

    PubMed

    Nazemi, K; Moztarzadeh, F; Jalali, N; Asgari, S; Mozafari, M

    2014-01-01

    The functionality of tissue engineering scaffolds can be enhanced by localized delivery of appropriate biological macromolecules incorporated within biodegradable nanoparticles. In this research, chitosan/58 S-bioactive glass (58 S-BG) containing poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been prepared and then characterized. The effects of further addition of 58 S-BG on the structure of scaffolds have been investigated to optimize the characteristics of the scaffolds for bone tissue engineering applications. The results showed that the scaffolds had high porosity with open pores. It was also shown that the porosity decreased with increasing 58 S-BG content. Furthermore, the PLGA nanoparticles were homogenously distributed within the scaffolds. According to the obtained results, the nanocomposites could be considered as highly bioactive bone tissue engineering scaffolds with the potential of localized delivery of biological macromolecules.

  18. Two-step nanoprecipitation for the production of protein-loaded PLGA nanospheres

    PubMed Central

    Morales-Cruz, Moraima; Flores-Fernández, Giselle M.; Morales-Cruz, Myreisa; Orellano, Elsie A.; Rodriguez-Martinez, José A.; Ruiz, Mercedes; Griebenow, Kai

    2012-01-01

    One of the first methods to encapsulate drugs within polymer nanospheres was developed by Fessi and coworkers in 1989 and consisted of one-step nanoprecipitation based on solvent displacement. However, proteins are poorly encapsulated within polymer nanoparticles using this method because of their limited solubility in organic solvents. To overcome this limitation, we developed a two-step nanoprecipitation method and encapsulated various proteins with high efficiency into poly(lactic-co-glycolic)acid (PLGA) nanospheres (NP). In this method, a protein nanoprecipitation step is used first followed by a second polymer nanoprecipitation step. Two model enzymes, lysozyme and α-chymotrypsin, were used for the optimization of the method. We obtained encapsulation efficiencies of >70%, an amount of buffer-insoluble protein aggregates of typically <2%, and a high residual activity of typically >90%. The optimum conditions identified for lysozyme were used to successfully encapsulate cytochrome c(Cyt-c), an apoptosis-initiating basic protein of similar size, to verify reproducibility of the encapsulation procedure. The size of the Cyt-c loaded-PLGA nanospheres was around 300–400 nm indicating the potential of the delivery system to passively target tumors. Cell viability studies, using a human cervical cancer cell line (HeLa), demonstrate excellent biocompatibility of the PLGA nanoparticles. PLGA nanoparticles carrying encapsulated Cyt-c were not efficient in causing apoptosis presumably because PLGA nanoparticles are not efficiently taken up by the cells. Future systems will have to be optimized to ascertain efficient cellular uptake of the nanoparticles by, e.g., surface modification with receptor ligands. PMID:23316451

  19. cmRNA/lipoplex encapsulation in PLGA microspheres enables transfection via calcium phosphate cement (CPC)/PLGA composites.

    PubMed

    Utzinger, Maximilian; Jarzebinska, Anita; Haag, Nicolas; Schweizer, Martin; Winter, Gerhard; Dohmen, Christian; Rudolph, Carsten; Plank, Christian

    2017-03-10

    In this study lipoplexes containing chemically modified messenger RNA (cmRNA) were incorporated into poly (lactic-co-glycolic acid) (PLGA) microspheres via water-in-oil-in-water (W/O/W) double emulsion solvent evaporation technique. The nanoparticle encapsulation by microparticle formation was optimized to achieve lipoplex release and maximum transfection efficiency in surrounding cells. It was possible to adjust characteristic features in surface topology and size of the PLGA-microspheres by varying the extent of lipoplex loading into the polymer matrix. The partial release of lipids and mRNA out of the microparticle system, their accumulation in cells and the production of encoded protein were visualized via fluorescence microscopy. These bioactive microspheres, containing cmRNA bearing lipoplexes, were developed for the incorporation of a therapeutic component into injectable calcium phosphate cements (CPC). Due to the incorporation of PLGA/lipoplex microspheres as a degradable entity, the porosity of the cement phase could additionally be adjusted. This approach of complex nanoparticle incorporation into polymer/cement composites represents a promising example for combining transcript therapy with biomechanical engineering.

  20. Thermodynamic Insights and Conceptual Design of Skin-Sensitive Chitosan Coated Ceramide/PLGA Nanodrug for Regeneration of Stratum Corneum on Atopic Dermatitis

    PubMed Central

    Jung, Sang-Myung; Yoon, Gwang Heum; Lee, Hoo Chul; Jung, Moon Hee; Yu, Sun Il; Yeon, Seung Ju; Min, Seul Ki; Kwon, Yeo Seon; Hwang, Jin Ha; Shin, Hwa Sung

    2015-01-01

    Atopic dermatitis (AD) is a complex skin disease primarily characterized by psoriasis of the stratum corneum. AD drugs have usually been used in acidic and hydrophilic solvents to supply moisture and prevent lipid defects. Ceramide is a typical treatment agent to regenerate the stratum corneum and relieve symptoms of AD. However, ceramide has limitation on direct use for skin because of its low dispersion properties in hydrophilic phase and side effects at excessive treatment. In this study, ceramide imbedded PLGA nanoparticles were developed with chitosan coating (Chi-PLGA/Cer) to overcome this problem. The chitosan coating enhanced initial adherence to the skin and prevented the initial burst of ceramide, but was degraded by the weakly acidic nature of skin, resulting in controlled release of ceramide with additional driving force of the squeezed PLGA nanoparticles. Additionally, the coating kinetics of chitosan were controlled by manipulating the reaction conditions and then mathematically modeled. The Chi-PLGA/Cer was not found to be cytotoxic and ceramide release was controlled by pH, temperature, and chitosan coating. Finally, Chi-PLGA/Cer was demonstrated to be effective at stratum corneum regeneration in a rat AD model. Overall, the results presented herein indicated that Chi-PLGA/Cer is a novel nanodrug for treatment of AD. PMID:26666701

  1. Thermodynamic Insights and Conceptual Design of Skin-Sensitive Chitosan Coated Ceramide/PLGA Nanodrug for Regeneration of Stratum Corneum on Atopic Dermatitis.

    PubMed

    Jung, Sang-Myung; Yoon, Gwang Heum; Lee, Hoo Chul; Jung, Moon Hee; Yu, Sun Il; Yeon, Seung Ju; Min, Seul Ki; Kwon, Yeo Seon; Hwang, Jin Ha; Shin, Hwa Sung

    2015-12-15

    Atopic dermatitis (AD) is a complex skin disease primarily characterized by psoriasis of the stratum corneum. AD drugs have usually been used in acidic and hydrophilic solvents to supply moisture and prevent lipid defects. Ceramide is a typical treatment agent to regenerate the stratum corneum and relieve symptoms of AD. However, ceramide has limitation on direct use for skin because of its low dispersion properties in hydrophilic phase and side effects at excessive treatment. In this study, ceramide imbedded PLGA nanoparticles were developed with chitosan coating (Chi-PLGA/Cer) to overcome this problem. The chitosan coating enhanced initial adherence to the skin and prevented the initial burst of ceramide, but was degraded by the weakly acidic nature of skin, resulting in controlled release of ceramide with additional driving force of the squeezed PLGA nanoparticles. Additionally, the coating kinetics of chitosan were controlled by manipulating the reaction conditions and then mathematically modeled. The Chi-PLGA/Cer was not found to be cytotoxic and ceramide release was controlled by pH, temperature, and chitosan coating. Finally, Chi-PLGA/Cer was demonstrated to be effective at stratum corneum regeneration in a rat AD model. Overall, the results presented herein indicated that Chi-PLGA/Cer is a novel nanodrug for treatment of AD.

  2. Comparison of cellular effects of starch-coated SPIONs and poly(lactic-co-glycolic acid) matrix nanoparticles on human monocytes

    PubMed Central

    Gonnissen, Dominik; Qu, Ying; Langer, Klaus; Öztürk, Cengiz; Zhao, Yuliang; Chen, Chunying; Seebohm, Guiscard; Düfer, Martina; Fuchs, Harald; Galla, Hans-Joachim; Riehemann, Kristina

    2016-01-01

    Within the last years, progress has been made in the knowledge of the properties of medically used nanoparticles and their toxic effects, but still, little is known about their influence on cellular processes of immune cells. The aim of our comparative study was to present the influence of two different nanoparticle types on subcellular processes of primary monocytes and the leukemic monocyte cell line MM6. We used core-shell starch-coated superparamagnetic iron oxide nanoparticles (SPIONs) and matrix poly(lactic-co-glycolic acid) (PLGA) nanoparticles for our experiments. In addition to typical biocompatibility testing like the detection of necrosis or secretion of interleukins (ILs), we investigated the impact of these nanoparticles on the actin cytoskeleton and the two voltage-gated potassium channels Kv1.3 and Kv7.1. Induction of necrosis was not seen for PLGA nanoparticles and SPIONs in primary monocytes and MM6 cells. Likewise, no alteration in secretion of IL-1β and IL-10 was detected under the same experimental conditions. In contrast, IL-6 secretion was exclusively downregulated in primary monocytes after contact with both nanoparticles. Two-electrode voltage clamp experiments revealed that both nanoparticles reduce currents of the aforementioned potassium channels. The two nanoparticles differed significantly in their impact on the actin cytoskeleton, demonstrated via atomic force microscopy elasticity measurement and phalloidin staining. While SPIONs led to the disruption of the respective cytoskeleton, PLGA did not show any influence in both experimental setups. The difference in the effects on ion channels and the actin cytoskeleton suggests that nanoparticles affect these subcellular components via different pathways. Our data indicate that the alteration of the cytoskeleton and the effect on ion channels are new parameters that describe the influence of nanoparticles on cells. The results are highly relevant for medical application and further

  3. Comparison of cellular effects of starch-coated SPIONs and poly(lactic-co-glycolic acid) matrix nanoparticles on human monocytes.

    PubMed

    Gonnissen, Dominik; Qu, Ying; Langer, Klaus; Öztürk, Cengiz; Zhao, Yuliang; Chen, Chunying; Seebohm, Guiscard; Düfer, Martina; Fuchs, Harald; Galla, Hans-Joachim; Riehemann, Kristina

    Within the last years, progress has been made in the knowledge of the properties of medically used nanoparticles and their toxic effects, but still, little is known about their influence on cellular processes of immune cells. The aim of our comparative study was to present the influence of two different nanoparticle types on subcellular processes of primary monocytes and the leukemic monocyte cell line MM6. We used core-shell starch-coated superparamagnetic iron oxide nanoparticles (SPIONs) and matrix poly(lactic-co-glycolic acid) (PLGA) nanoparticles for our experiments. In addition to typical biocompatibility testing like the detection of necrosis or secretion of interleukins (ILs), we investigated the impact of these nanoparticles on the actin cytoskeleton and the two voltage-gated potassium channels Kv1.3 and Kv7.1. Induction of necrosis was not seen for PLGA nanoparticles and SPIONs in primary monocytes and MM6 cells. Likewise, no alteration in secretion of IL-1β and IL-10 was detected under the same experimental conditions. In contrast, IL-6 secretion was exclusively downregulated in primary monocytes after contact with both nanoparticles. Two-electrode voltage clamp experiments revealed that both nanoparticles reduce currents of the aforementioned potassium channels. The two nanoparticles differed significantly in their impact on the actin cytoskeleton, demonstrated via atomic force microscopy elasticity measurement and phalloidin staining. While SPIONs led to the disruption of the respective cytoskeleton, PLGA did not show any influence in both experimental setups. The difference in the effects on ion channels and the actin cytoskeleton suggests that nanoparticles affect these subcellular components via different pathways. Our data indicate that the alteration of the cytoskeleton and the effect on ion channels are new parameters that describe the influence of nanoparticles on cells. The results are highly relevant for medical application and further

  4. pH-dependent antibacterial effects on oral microorganisms through pure PLGA implants and composites with nanosized bioactive glass.

    PubMed

    Hild, Nora; Tawakoli, Pune N; Halter, Jonas G; Sauer, Bärbel; Buchalla, Wolfgang; Stark, Wendelin J; Mohn, Dirk

    2013-11-01

    Biomaterials made of biodegradable poly(α-hydroxyesters) such as poly(lactide-co-glycolide) (PLGA) are known to decrease the pH in the vicinity of the implants. Bioactive glass (BG) is being investigated as a counteracting agent buffering the acidic degradation products. However, in dentistry the question arises whether an antibacterial effect is rather obtained from pure PLGA or from BG/PLGA composites, as BG has been proved to be antimicrobial. In the present study the antimicrobial properties of electrospun PLGA and BG45S5/PLGA fibres were investigated using human oral bacteria (specified with mass spectrometry) incubated for up to 24 h. BG45S5 nanoparticles were prepared by flame spray synthesis. The change in colony-forming units (CFU) of the bacteria was correlated with the pH of the medium during incubation. The morphology and structure of the scaffolds as well as the appearance of the bacteria were followed bymicroscopy. Additionally, we studied if the presence of BG45S5 had an influence on the degradation speed of the polymer. Finally, it turned out that the pH increase induced by the presence of BG45S5 in the scaffold did not last long enough to show a reduction in CFU. On the contrary, pure PLGA demonstrated antibacterial properties that should be taken into consideration when designing biomaterials for dental applications.

  5. Nanoparticles modified with multiple organic acids

    NASA Technical Reports Server (NTRS)

    Cook, Ronald Lee (Inventor); Luebben, Silvia DeVito (Inventor); Myers, Andrew William (Inventor); Smith, Bryan Matthew (Inventor); Elliott, Brian John (Inventor); Kreutzer, Cory (Inventor); Wilson, Carolina (Inventor); Meiser, Manfred (Inventor)

    2007-01-01

    Surface-modified nanoparticles of boehmite, and methods for preparing the same. Aluminum oxyhydroxide nanoparticles are surface modified by reaction with selected amounts of organic acids. In particular, the nanoparticle surface is modified by reactions with two or more different carboxylic acids, at least one of which is an organic carboxylic acid. The product is a surface modified boehmite nanoparticle that has an inorganic aluminum oxyhydroxide core, or part aluminum oxyhydroxide core and a surface-bonded organic shell. Organic carboxylic acids of this invention contain at least one carboxylic acid group and one carbon-hydrogen bond. One embodiment of this invention provides boehmite nanoparticles that have been surface modified with two or more acids one of which additional carries at least one reactive functional group. Another embodiment of this invention provides boehmite nanoparticles that have been surface modified with multiple acids one of which has molecular weight or average molecular weight greater than or equal to 500 Daltons. Yet, another embodiment of this invention provides boehmite nanoparticles that are surface modified with two or more acids one of which is hydrophobic in nature and has solubility in water of less than 15 by weight. The products of the methods of this invention have specific useful properties when used in mixture with liquids, as filler in solids, or as stand-alone entities.

  6. Nanoparticles modified with multiple organic acids

    DOEpatents

    Cook, Ronald Lee; Luebben, Silvia DeVito; Myers, Andrew William; Smith, Bryan Matthew; Elliott, Brian John; Kreutzer, Cory; Wilson, Carolina; Meiser, Manfred

    2007-07-17

    Surface-modified nanoparticles of boehmite, and methods for preparing the same. Aluminum oxyhydroxide nanoparticles are surface modified by reaction with selected amounts of organic acids. In particular, the nanoparticle surface is modified by reactions with two or more different carboxylic acids, at least one of which is an organic carboxylic acid. The product is a surface modified boehmite nanoparticle that has an inorganic aluminum oxyhydroxide core, or part aluminum oxyhydroxide core and a surface-bonded organic shell. Organic carboxylic acids of this invention contain at least one carboxylic acid group and one carbon-hydrogen bond. One embodiment of this invention provides boehmite nanoparticles that have been surface modified with two or more acids one of which additional carries at least one reactive functional group. Another embodiment of this invention provides boehmite nanoparticles that have been surface modified with multiple acids one of which has molecular weight or average molecular weight greater than or equal to 500 Daltons. Yet, another embodiment of this invention provides boehmite nanoparticles that are surface modified with two or more acids one of which is hydrophobic in nature and has solubility in water of less than 15 by weight. The products of the methods of this invention have specific useful properties when used in mixture with liquids, as filler in solids, or as stand-alone entities.

  7. Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules

    PubMed Central

    Wen, Xingxing; Ding, Shan; Cai, Hui; Wang, Junyi; Wen, Lu; Yang, Fan; Chen, Gang

    2016-01-01

    Targeted drug delivery to outer hair cells (OHCs) in the cochlea by nanomedicine strategies forms an effective therapeutic approach for treating hearing loss. Surface chemistry plays a deciding role in nanoparticle (NP) biodistribution, but its influence on such distribution in the cochlea remains largely unknown. Herein, we report the first systematic comparison of poly(lactic/glycolic acid) nanoparticles (PLGA NPs) with or without surface modification of hydrophilic molecules for optimizing the delivery to OHCs both in vitro and in vivo. NPs that were surface modified with poloxamer 407 (P407), chitosan, or methoxy poly(ethylene glycol) and the unmodified NPs were highly biocompatible with L929 and House Ear Institute-organ of Corti 1 cells as well as cochlear tissues. Interestingly, among all the examined NPs, P407-PLGA NPs showed the greatest cellular uptake and prominent fluorescence in cochlear imaging. More importantly, we provide novel evidence that the surface-modified NPs reached the organ of Corti and were transported into the OHCs at a higher level. Together, these observations suggest that surface modification with hydrophilic molecules will allow future clinical applications of PLGA NPs, especially P407-PLGA NPs, in efficient hearing loss therapy. PMID:27877041

  8. Surface Mechanical and Rheological Behaviors of Biocompatible Poly((D,L-lactic acid-ran-glycolic acid)-block-ethylene glycol) (PLGA-PEG) and Poly((D,L-lactic acid-ran-glycolic acid-ran-ε-caprolactone)-block-ethylene glycol) (PLGACL-PEG) Block Copolymers at the Air-Water Interface.

    PubMed

    Kim, Hyun Chang; Lee, Hoyoung; Khetan, Jawahar; Won, You-Yeon

    2015-12-29

    Air-water interfacial monolayers of poly((D,L-lactic acid-ran-glycolic acid)-block-ethylene glycol) (PLGA-PEG) exhibit an exponential increase in surface pressure under high monolayer compression. In order to understand the molecular origin of this behavior, a combined experimental and theoretical investigation (including surface pressure-area isotherm, X-ray reflectivity (XR) and interfacial rheological measurements, and a self-consistent field (SCF) theoretical analysis) was performed on air-water monolayers formed by a PLGA-PEG diblock copolymer and also by a nonglassy analogue of this diblock copolymer, poly((D,L-lactic acid-ran-glycolic acid-ran-caprolactone)-block-ethylene glycol) (PLGACL-PEG). The combined results of this study show that the two mechanisms, i.e., the glass transition of the collapsed PLGA film and the lateral repulsion of the PEG brush chains that occur simultaneously under lateral compression of the monolayer, are both responsible for the observed PLGA-PEG isotherm behavior. Upon cessation of compression, the high surface pressure of the PLGA-PEG monolayer typically relaxes over time with a stretched exponential decay, suggesting that in this diblock copolymer situation, the hydrophobic domain formed by the PLGA blocks undergoes glass transition in the high lateral compression state, analogously to the PLGA homopolymer monolayer. In the high PEG grafting density regime, the contribution of the PEG brush chains to the high monolayer surface pressure is significantly lower than what is predicted by the SCF model because of the many-body attraction among PEG segments (referred to in the literature as the "n-cluster" effects). The end-grafted PEG chains were found to be protein resistant even under the influence of the "n-cluster" effects.

  9. CD40-targeted dendritic cell delivery of PLGA-nanoparticle vaccines induce potent anti-tumor responses.

    PubMed

    Rosalia, Rodney A; Cruz, Luis J; van Duikeren, Suzanne; Tromp, Angelino T; Silva, Ana L; Jiskoot, Wim; de Gruijl, Tanja; Löwik, Clemens; Oostendorp, Jaap; van der Burg, Sjoerd H; Ossendorp, Ferry

    2015-02-01

    Dendritic cells (DC) play a prominent role in the priming of CD8(+) T cells. Vaccination is a promising treatment to boost tumor-specific CD8(+) T cells which is crucially dependent on adequate delivery of the vaccine to DC. Upon subcutaneous (s.c.) injection, only a small fraction of the vaccine is delivered to DC whereas the majority is cleared by the body or engulfed by other immune cells. To overcome this, we studied vaccine delivery to DC via CD40-targeting using a multi-compound particulate vaccine with the aim to induce potent CD8(+) T cell responses. To this end, biodegradable poly(lactic-co-glycolic acid) nanoparticles (NP) were formulated encapsulating a protein Ag, Pam3CSK4 and Poly(I:C) and coated with an agonistic αCD40-mAb (NP-CD40). Targeting NP to CD40 led to very efficient and selective delivery to DC in vivo upon s.c. injection and improved priming of CD8(+) T cells against two independent tumor associated Ag. Therapeutic application of NP-CD40 enhanced tumor control and prolonged survival of tumor-bearing mice. We conclude that CD40-mediated delivery to DC of NP-vaccines, co-encapsulating Ag and adjuvants, efficiently drives specific T cell responses, and therefore, is an attractive method to improve the efficacy of protein based cancer vaccines undergoing clinical testing in the clinic.

  10. Polymeric Nanoparticles for Pulmonary Protein and DNA Delivery

    PubMed Central

    Menon, Jyothi U.; Ravikumar, Priya; Pise, Amruta; Gyawali, Dipendra; Hsia, Connie C.W.; Nguyen, Kytai T.

    2014-01-01

    Polymeric nanoparticles (NPs) are promising carriers of biological agents to lung due to advantages including biocompatibility, ease of surface modification, localized action and reduced systemic toxicity. However, there have been no studies extensively characterizing and comparing the behavior of polymeric NPs for pulmonary protein/DNA delivery both in vitro and in vivo. We screened six polymeric NPs: gelatin, chitosan, alginate, poly lactic-co-glycolic acid (PLGA), PLGA-chitosan, and PLGA-polyethylene glycol (PEG), for inhalational protein/ DNA delivery. All NPs except PLGA-PEG and alginate were <300 nm in size with bi-phasic core compound release profile. Gelatin, PLGA NPs and PLGA-PEG NPs remained stable in deionized water, serum, saline and simulated lung fluid (Gamble’s solution) over 5 days. PLGA-based NPs and natural polymer NPs exhibited highest cytocompatibility and dose-dependent in vitro uptake respectively by human alveolar type-1 epithelial cells. Based on these profiles, gelatin and PLGA NPs were used to encapsulate a) plasmid DNA encoding yellow fluorescent protein (YFP) or b) rhodamine-conjugated erythropoietin (EPO) for inhalational delivery to rats. Following a single inhalation, widespread pulmonary EPO distribution persisted for up to 10 days while increasing YFP expression was observed for at least 7 days for both NPs. The overall results support both PLGA and gelatin NPs as promising carriers for pulmonary protein/DNA delivery. PMID:24512977

  11. Humidity-dependent compression-induced glass transition of the air–water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA)

    SciTech Connect

    Kim, Hyun Chang; Lee, Hoyoung; Jung, Hyunjung; Choi, Yun -Hwa; Meron, Mati; Lin, Binhua; Bang, Joona; Won, You -Yeon

    2015-08-26

    Constant rate compression isotherms of the air–water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA)show a distinct feature of an exponential increase in surface pressure in the high surface polymer concentration regime. We have previously demonstrated that this abrupt increase in surface pressure is linked to the glass transition of the polymer film, but the detailed mechanism of this process is not understood. In order to obtain a molecular-level understanding of this behavior, we performed extensive characterizations of the surface mechanical, structural and rheological properties of Langmuir PLGA films at the air–water interface, using combined experimental techniques including the Langmuir film balance, X-ray reflectivity and double-wall-ring interfacial rheometry methods.

  12. Formulation and optimization of coated PLGA - Zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency.

    PubMed

    Peter Christoper, G V; Vijaya Raghavan, C; Siddharth, K; Siva Selva Kumar, M; Hari Prasad, R

    2014-04-01

    In the current study zidovudine loaded PLGA nanoparticles were prepared, coated and further investigated for its effectiveness in brain targeting. IR and DSC studies were performed to determine the interaction between excipients used and to find out the nature of drug in the formulation. Formulations were prepared by adopting 2(3) factorial designs to evaluate the effects of process and formulation variables. The prepared formulations were subjected for in vitro and in vivo evaluations. In vitro evaluations showed particle size below 100 nm, entrapment efficiency of formulations ranges of 28-57%, process yield of 60-76% was achieved and drug release for the formulations were in the range of 50-85%. The drug release from the formulations was found to follow Higuchi release pattern, n-value obtained after Korsemeyer plot was in the range of 0.56-0.78. In vivo evaluations were performed in mice after intraperitoneal administration of zidovudine drug solution, uncoated and coated formulation. Formulation when coated with Tween 80 achieved a higher concentration in the brain than that of the drug in solution and of the uncoated formulation. Stability studies indicated that there was no degradation of the drug in the formulation after 90 days of preparation when stored in refrigerated condition.

  13. Formulation and optimization of coated PLGA – Zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency

    PubMed Central

    Peter Christoper, G.V.; Vijaya Raghavan, C.; Siddharth, K.; Siva Selva Kumar, M.; Hari Prasad, R.

    2013-01-01

    In the current study zidovudine loaded PLGA nanoparticles were prepared, coated and further investigated for its effectiveness in brain targeting. IR and DSC studies were performed to determine the interaction between excipients used and to find out the nature of drug in the formulation. Formulations were prepared by adopting 23 factorial designs to evaluate the effects of process and formulation variables. The prepared formulations were subjected for in vitro and in vivo evaluations. In vitro evaluations showed particle size below 100 nm, entrapment efficiency of formulations ranges of 28–57%, process yield of 60–76% was achieved and drug release for the formulations were in the range of 50–85%. The drug release from the formulations was found to follow Higuchi release pattern, n–value obtained after Korsemeyer plot was in the range of 0.56–0.78. In vivo evaluations were performed in mice after intraperitoneal administration of zidovudine drug solution, uncoated and coated formulation. Formulation when coated with Tween 80 achieved a higher concentration in the brain than that of the drug in solution and of the uncoated formulation. Stability studies indicated that there was no degradation of the drug in the formulation after 90 days of preparation when stored in refrigerated condition. PMID:24648825

  14. Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery.

    PubMed

    Vasconcelos, Aimee; Vega, Estefania; Pérez, Yolanda; Gómara, María J; García, María Luisa; Haro, Isabel

    2015-01-01

    In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)-polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen's egg test-chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery.

  15. Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery

    PubMed Central

    Vasconcelos, Aimee; Vega, Estefania; Pérez, Yolanda; Gómara, María J; García, María Luisa; Haro, Isabel

    2015-01-01

    In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)–polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test–chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery. PMID:25670897

  16. Radiosensitization of TPGS-emulsified docetaxel-loaded poly(lactic-co-glycolic acid) nanoparticles in CNE-1 and A549 cells.

    PubMed

    Shi, Wei; Yuan, Yin; Chu, Min; Zhao, Shuang; Song, Qingle; Mu, Xiaoqian; Xu, Shuangbing; Zhang, Zhiping; Yang, Kunyu

    2016-03-01

    Docetaxel is among the most effective radiosensitizers. It is widely used as radiosensitizer in many tumors, including head and neck carcinoma. Nevertheless, poor solubility and severe hypersensitivity limit its clinical use and its therapeutic effect remains to be improved. In this study, docetaxel-loaded polymeric nanoparticles were prepared by nanoprecipitation method to be new radiosensitizer with lower side effects and higher efficacy. The physiochemical characteristics of the nanoparticles were studied. Two human tumor cell lines which are resistant to radiotherapy were used in this research. We have compared the radioenhancement efficacy of docetaxel-loaded nanoparticles with docetaxel in A549 and CNE-1 cells. Compared with docetaxel, radiosensitization of docetaxel-loaded nanoparticles was improved significantly (sensitization enhancement ratio in A549 increased 1.24-fold to 1.68-fold when the radiation was applied 2 h after the drug, p < 0.01, sensitization enhancement ratio in CNE-1 increased 1.32-fold to 1.61-fold, p < 0.05). We explored the mechanisms for the radiosensitization efficiency and the difference between docetaxel and docetaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, promoted apoptosis and the role of D-alpha-tocopheryl polyethylene glycol 1000 succinate which will enhance the cell uptake and inhibit the multiple drug resistance. Moreover, the radiosensitization efficacy of docetaxel-loaded nanoparticles was more prominent than docetaxel. In conclusion, tocopheryl polyethylene glycol 1000 succinate-emulsified docetaxel-loaded PLGA nanoparticles were more efficacious and fewer adverse effects were observed than with the commercial docetaxel formulation. Thus, PLGA nanoparticles hold promise as a radiosensitizing agent.

  17. Acid-functionalized nanoparticles for biomass hydrolysis

    NASA Astrophysics Data System (ADS)

    Pena Duque, Leidy Eugenia

    Cellulosic ethanol is a renewable source of energy. Lignocellulosic biomass is a complex material composed mainly of cellulose, hemicellulose, and lignin. Biomass pretreatment is a required step to make sugar polymers liable to hydrolysis. Mineral acids are commonly used for biomass pretreatment. Using acid catalysts that can be recovered and reused could make the process economically more attractive. The overall goal of this dissertation is the development of a recyclable nanocatalyst for the hydrolysis of biomass sugars. Cobalt iron oxide nanoparticles (CoFe2O4) were synthesized to provide a magnetic core that could be separated from reaction using a magnetic field and modified to carry acid functional groups. X-ray diffraction (XRD) confirmed the crystal structure was that of cobalt spinel ferrite. CoFe2O4 were covered with silica which served as linker for the acid functions. Silica-coated nanoparticles were functionalized with three different acid functions: perfluoropropyl-sulfonic acid, carboxylic acid, and propyl-sulfonic acid. Transmission electron microscope (TEM) images were analyzed to obtain particle size distributions of the nanoparticles. Total carbon, nitrogen, and sulfur were quantified using an elemental analyzer. Fourier transform infra-red spectra confirmed the presence of sulfonic and carboxylic acid functions and ion-exchange titrations accounted for the total amount of catalytic acid sites per nanoparticle mass. These nanoparticles were evaluated for their performance to hydrolyze the beta-1,4 glycosidic bond of the cellobiose molecule. Propyl-sulfonic (PS) and perfluoropropyl-sulfonic (PFS) acid functionalized nanoparticles catalyzed the hydrolysis of cellobiose significantly better than the control. PS and PFS were also evaluated for their capacity to solubilize wheat straw hemicelluloses and performed better than the control. Although PFS nanoparticles were stronger acid catalysts, the acid functions leached out of the nanoparticle during

  18. 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

  19. Heuristic modeling of macromolecule release from PLGA microspheres

    PubMed Central

    Szlęk, Jakub; Pacławski, Adam; Lau, Raymond; Jachowicz, Renata; Mendyk, Aleksander

    2013-01-01

    Dissolution of protein macromolecules from poly(lactic-co-glycolic acid) (PLGA) particles is a complex process and still not fully understood. As such, there are difficulties in obtaining a predictive model that could be of fundamental significance in design, development, and optimization for medical applications and toxicity evaluation of PLGA-based multiparticulate dosage form. In the present study, two models with comparable goodness of fit were proposed for the prediction of the macromolecule dissolution profile from PLGA micro- and nanoparticles. In both cases, heuristic techniques, such as artificial neural networks (ANNs), feature selection, and genetic programming were employed. Feature selection provided by fscaret package and sensitivity analysis performed by ANNs reduced the original input vector from a total of 300 input variables to 21, 17, 16, and eleven; to achieve a better insight into generalization error, two cut-off points for every method was proposed. The best ANNs model results were obtained by monotone multi-layer perceptron neural network (MON-MLP) networks with a root-mean-square error (RMSE) of 15.4, and the input vector consisted of eleven inputs. The complicated classical equation derived from a database consisting of 17 inputs was able to yield a better generalization error (RMSE) of 14.3. The equation was characterized by four parameters, thus feasible (applicable) to standard nonlinear regression techniques. Heuristic modeling led to the ANN model describing macromolecules release profiles from PLGA microspheres with good predictive efficiency. Moreover genetic programming technique resulted in classical equation with comparable predictability to the ANN model. PMID:24348037

  20. PLGA/alginate composite microspheres for hydrophilic protein delivery.

    PubMed

    Zhai, Peng; Chen, X B; Schreyer, David J

    2015-11-01

    Poly(lactic-co-glycolic acid) (PLGA) microspheres and PLGA/alginate composite microspheres were prepared by a novel double emulsion and solvent evaporation technique and loaded with bovine serum albumin (BSA) or rabbit anti-laminin antibody protein. The addition of alginate and the use of a surfactant during microsphere preparation increased the encapsulation efficiency and reduced the initial burst release of hydrophilic BSA. Confocal laser scanning microcopy (CLSM) of BSA-loaded PLGA/alginate composite microspheres showed that PLGA, alginate, and BSA were distributed throughout the depths of microspheres; no core/shell structure was observed. Scanning electron microscopy revealed that PLGA microspheres erode and degrade more quickly than PLGA/alginate composite microspheres. When loaded with anti-laminin antibody, the function of released antibody was well preserved in both PLGA and PLGA/alginate composite microspheres. The biocompatibility of PLGA and PLGA/alginate microspheres were examined using four types of cultured cell lines, representing different tissue types. Cell survival was variably affected by the inclusion of alginate in composite microspheres, possibly due to the sensitivity of different cell types to excess calcium that may be released from the calcium cross-linked alginate.

  1. Evaluating the Properties of Poly(lactic-co-glycolic acid) Nanoparticle Formulations Encapsulating a Hydrophobic Drug by Using the Quality by Design Approach.

    PubMed

    Kozaki, Masato; Kobayashi, Shin-Ichiro; Goda, Yukihiro; Okuda, Haruhiro; Sakai-Kato, Kumiko

    2017-01-01

    We applied the Quality by Design (QbD) approach to the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulations encapsulating triamcinolone acetonide, and the critical process parameters (CPPs) were identified to clarify the correlations between critical quality attributes and CPPs. Quality risk management was performed by using an Ishikawa diagram and experiments with a fractional factorial design (ANOVA). The CPPs for particle size were PLGA concentration and rotation speed, and the CPP for relative drug loading efficiency was the poor solvent to good solvent volume ratio. By assessing the mutually related factors in the form of ratios, many factors could be efficiently considered in the risk assessment. We found a two-factor interaction between rotation speed and rate of addition of good solvent by using a fractional factorial design with resolution V. The system was then extended by using a central composite design, and the results obtained were visualized by using the response surface method to construct a design space. Our research represents a case study of the application of the QbD approach to pharmaceutical development, including formulation screening, by taking actual production factors into consideration. Our findings support the feasibility of using a similar approach to nanoparticle formulations under development. We could establish an efficient method of analyzing the CPPs of PLGA nanoparticles by using a QbD approach.

  2. Nanoparticles made of multi-block copolymer of lactic acid and ethylene glycol containing periodic side-chain carboxyl groups for oral delivery of cyclosporine A

    PubMed Central

    Ankola, D. D.; Battisti, A.; Solaro, R.; Kumar, M. N. V. Ravi

    2010-01-01

    The purpose of this study was to evaluate the potential of new carboxylated multi-block copolymer of lactic acid and ethylene glycol (EL14) for nanoparticle (NP) formation and their ability to deliver high molecular weight hydrophobic drug—cyclosporine A (CsA). CsA-loaded EL14 NPs were compared with traditional poly(lactide-co-glycolide) (PLGA) NPs, both prepared by emulsion–diffusion–evaporation process. On the one hand, the increase in drug payload from 10 to 30 per cent for EL14 NPs showed no difference in particle size, however the entrapment efficiency tends to decrease from 50 to 43 per cent; on the other hand, the more hydrophobic PLGA showed an increasing trend in entrapment efficiency from 20 to 62 per cent with increasing particle size. Over 90 per cent of CsA was released in vitro from both the nanoparticulates; however, the release was much slower in the case of more hydrophobic PLGA. On in vivo evaluation in rats, the NPs made of EL14 showed a higher Cmax, a faster Tmax and enhanced tissue levels to that of PLGA that are crucial for CsA's activity and toxicity; however, the overall bioavailability of the nanoparticulates was similar and higher than Neoral. Together these data demonstrate the feasibility of NPs made of low molecular weight, hydrophilic polymer EL14 for efficient delivery of CsA. PMID:20504806

  3. Pulsatile drug release from PLGA hollow microspheres by controlling the permeability of their walls with a magnetic field.

    PubMed

    Chiang, Wei-Lun; Ke, Cherng-Jyh; Liao, Zi-Xian; Chen, San-Yuan; Chen, Fu-Rong; Tsai, Chun-Ying; Xia, Younan; Sung, Hsing-Wen

    2012-12-07

    Pulsatile release: When a high-frequency magnetic field is applied, heat will be generated by coupling to the iron oxide nanoparticles encapsulated in the shells of PLGA hollow microspheres. As the temperature approaches the T(g) of PLGA, the polymer chains become more mobile, subsequently increasing the free volume of PLGA matrix and significantly enhancing the diffusion of drug molecules.

  4. Hydrophilic poly (ethylene glycol) capped poly (lactic-co-glycolic) acid nanoparticles for subcutaneous delivery of insulin in diabetic rats.

    PubMed

    S, Saravanan; S, Malathi; P S L, Sesh; S, Selvasubramanian; S, Balasubramanian; V, Pandiyan

    2017-02-01

    The aim of the present study is to evaluate the effect of insulin loaded poly(ethylene glycol) capped poly(lactic-co-glycolic)acid nanoparticles (ISPPLG NPs) by subcutaneous administration in diabetic rats. A series of biodegradable low molecular weight PLGA [90/10 (PLG2) and 80/20 (PLG4)] copolymers were synthesized by melt polycondensation and their ISPPLG NPs were synthesized by water-oil-water (W/O/W) emulsion solvent evaporation method. The PLGA copolymers and their nanoparticles were characterized. The maximum encapsulation efficiency of ISPPLG4 NPs is 66% and the diameter of the nanoparticles is about 140nm. The in-vivo studies of ISPPLG NPs carried out in diabetic rats by subcutaneous administration show considerable reduction in serum glucose level along with partial restoration of tissue defense systems. Histopathological studies reveal that ISPPLG NPs could restore the damages caused by oxidants during hyperglycaemia. The subcutaneous administration of ISPPLG4 NPs is thus an effective method of reducing hyperglycaemia associated complications.

  5. Evaluation of PLGA containing anti-CTLA4 inhibited endometriosis progression by regulating CD4+CD25+Treg cells in peritoneal fluid of mouse endometriosis model.

    PubMed

    Liu, Qi; Ma, Pingchuan; Liu, Lanxia; Ma, Guilei; Ma, Jingjing; Liu, Xiaoxuan; Liu, Yijin; Lin, Wanjun; Zhu, Yingjun

    2017-01-01

    Our study investigated poly(lactic-co-glycolic acid) (PLGA) as protein delivery vehicles encapsulate CTLA-4-antibody (anti-CTLA-4) which is essential for CD4+CD25+Treg cells suppressive function exposing superior potential for inhibiting endometriosis progress in mouse model than single anti-CTLA-4. Anti-CTLA-4 loaded PLGA combined to ligands CTLA-4 in surface of CD4+CD25+Treg cells which distributed in peritoneal fluid of mouse endometriosis model. The particle size, zeta potential of the anti-CTLA-4 loaded nanoparticles was detected by dynamic light scattering. Morphology of nanoparticles was evaluated by transmission electron microscopy (TEM). Confocal laser scanning microscopy (CLSM) indicated distribution of anti-CTLA-4 with PLGA or without in peritoneal fluid. Cumulative anti-CTLA-4 release from nanoparticles was evaluated by Micro BCA assay. The percentage of CD4+CD25+Treg cells in peritoneal fluid was demonstrated by flow cytometer. In vitro experiment we co-culture ectopic endometrial cells (EEC) with isolated CD4+CD25+Treg cells in peritoneal fluid (PF), proliferation and invasion of ectopic endometrial cells (EEC) was measured by BrdU ELISA assay and Matrigel invasion assay. In comparison with anti-CTLA-4 without nanoparticles, the bioconjugates PLGA/anti-CTLA-4 were tolerated in peritoneal fluid with a controlled release of anti-CTLA-4 in 3, 7, 14days. Moreover, PLGA/anti-CTLA-4 had superior protective regulation ability to reduce level of CD4+CD25+Treg cells in peritoneal fluid. Most strikingly, in vitro experiment, PLGA/anti-CTLA-4 exhibited better ability in inhibiting proliferation and invasion of ectopic endometrial cells in co-culture system compared with anti-CTLA-4. Progressively, PLGA/anti-CTLA-4 had better suppressive activity to inhibited IL-10 and TGF-beta secreted by CD4+CD25+Treg cells which indicating that PLGA/anti-CTLA-4 suppressed cells proliferation and invasion through reduced IL-10 and TGF-beta production. Thus, PLGA/anti-CTLA-4 may

  6. Salmon calcitonin-loaded Eudragit® and Eudragit®-PLGA nanoparticles: in vitro and in vivo evaluation.

    PubMed

    Cetin, Meltem; Aktas, Mustafa Sinan; Vural, Imran; Ozturk, Murat

    2012-01-01

    The main objective of this study was to prepare salmon calcitonin (sCT)-loaded Eudragit®RSPO, Eudragit®L100 and Eudragit®-poly(lactic-co-glycolic acid) blend nanoparticles for in vitro and in vivo evaluation as an oral drug delivery system. The prepared nanoparticles ranged in size from 179.7 to 308.9 nm with a polydispersity index between 0.051 and 2.75, and had surface charges ~ -11 to +6 mV. Efficient sCT encapsulation and release was observed with all the nanoparticle formulations. The polymer type was an important factor that influenced the release characteristics and the in vivo hypocalcemic effect. Nanoparticle formulations were also prepared with sodium taurodeoxycholate (NaTDC) and characterized. No statistically significant difference was noted between the hypocalcemic effect of any of the nanoparticle formulations with and without NaTDC (p > 0.05). The use of Eudragit®RSPO nanoparticles appears to be a potential approach for the oral delivery of sCT.

  7. Comparison of sorafenib-loaded poly (lactic/glycolic) acid and DPPC liposome nanoparticles in the in vitro treatment of renal cell carcinoma.

    PubMed

    Liu, James; Boonkaew, Benjawan; Arora, Jaspreet; Mandava, Sree Harsha; Maddox, Michael M; Chava, Srinivas; Callaghan, Cameron; He, Jibao; Dash, Srikanta; John, Vijay T; Lee, Benjamin R

    2015-03-01

    The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 μM from 24 to 96 h, respectively. At maximum dosage and time (15 μM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 μM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities.

  8. PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol-gels for drug delivery.

    PubMed

    Cho, Hyunah; Gao, Jieming; Kwon, Glen S

    2016-10-28

    Poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles and poly(D,L-lactic-co-glycolic acid)-block-polyethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PLGA-b-PEG-b-PLGA) sol-gels have been extensively researched for systemic and localized drug delivery applications, respectively, and they have both progressed into humans for paclitaxel, an important yet poorly water-soluble chemotherapeutic agent. In this review article, preclinical and clinical research on PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol-gels that has focused on paclitaxel will be updated, and recent research on other poorly water-soluble anticancer agents and delivery of drug combinations (i.e. multi-drug delivery) that seeks synergistic anticancer efficacy will be summarized. PEG-b-PLA micelles are a first-generation platform for the systemic multi-delivery of poorly water soluble anticancer agents. PLGA-b-PEG-b-PLGA sol-gels are a first-generation platform for the localized multi-drug delivery of water-soluble and/or poorly water-soluble anticancer agents. In summary, PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol-gels may safely enable pre-clinical evaluation and clinical translation of poorly water-soluble anticancer agents, especially for promising, rapidly emerging anticancer combinations.

  9. Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability.

    PubMed

    Luo, Haitao; Jiang, Bingbing; Li, Bingyun; Li, Zhaoliang; Jiang, Bing-Hua; Chen, Yi Charlie

    2012-01-01

    Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles resulted in enhanced reduction of cancer cell viability. Among the nonionic polymeric nanoparticles, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nanoparticles incorporating kaempferol led to significant reduction in cell viability of both cancerous and normal cells. Poly(DL-lactic acid-co-glycolic acid) (PLGA) nanoparticles incorporating kaempferol resulted in enhanced reduction of cancer cell viability together with no significant reduction in cell viability of normal cells compared with kaempferol alone. Therefore, both PEO-PPO-PEO and PLGA nanoparticle formulations were effective in reducing cancer cell viability, while PLGA nanoparticles incorporating kaempferol had selective toxicity against cancer cells and normal cells. A PLGA nanoparticle formulation could be advantageous in the prevention and treatment of ovarian cancers. On the other hand, PEO-PPO-PEO nanoparticles incorporating kaempferol were more effective inhibitors of cancer cells, but they also significantly reduced the viability of normal cells. PEO-PPO-PEO nanoparticles incorporating kaempferol may be suitable as a cancer-targeting strategy, which could limit the effects of the nanoparticles on normal cells while retaining their potency against cancer cells. We

  10. PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread

    NASA Astrophysics Data System (ADS)

    Tang, Xiaolong; Liang, Yong; Liu, Xinkuang; Zhou, Shuping; Liu, Liang; Zhang, Fujina; Xie, Chunmei; Cai, Shuyu; Wei, Jia; Zhu, Yongqiang; Hou, Wei

    2015-10-01

    Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA- and SAHA + Nel-loaded nanoparticles can target latently infected CD4+ T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.

  11. Silymarin encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles: a prospective candidate for prostate cancer therapy.

    PubMed

    Snima, K S; Arunkumar, P; Jayakumar, R; Lakshmanan, Vinoth-Kumar

    2014-04-01

    Silymarin, a clinically proved hepato-protective herbal drug having significant anti-cancerous property towards prostate cancer, is inadequately utilized for cancer therapy due to its hydrophobic nature and poor bioavailability. In this work, we have developed silymarin Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in order to improve the therapeutic efficacy of silymarin towards prostate cancer by single emulsion solvent evaporation technique. The prepared nanoparticles had an encapsulation efficiency of 60% and a loading efficiency of 13%. The silymarin-PLGA NPs (SNPs) characterization, using DLS and SEM analysis revealed its size as less than 300 nm. FT-IR analysis confirmed encapsulation of silymarin by the SNPs, whereas XRD and TGA proved amorphous nature of the SNPs. In vitro drug release study demonstrated a slow and sustained release of encapsulated drug from the SNPs in physiological conditions. The hemocompatibility of the SNPs was established by in vitro hemolysis and coagulation assays. In vitro cell viability studies revealed preferential toxicity of SNPs towards prostate cancer cells (PC-3) compared to normal cells (Vero) in a dose dependant way. Cell uptake studies using confocal microscopy confirmed internalization of the SNPs by PC-3 cells. Furthermore, in vitro cell migration assay showed a concentration and time dependent inhibitory effect of SNPs on PC-3 cell migration. Finally, flow-cytometry based apoptosis assay suggested induction of apoptosis mediated death in PC-3 cells by the SNPs. Overall, the prepared SNPs proved as a promising candidate for prostate cancer therapy.

  12. Concepts and practices used to develop functional PLGA-based nanoparticulate systems

    PubMed Central

    Sah, Hongkee; Thoma, Laura A; Desu, Hari R; Sah, Edel; Wood, George C

    2013-01-01

    The functionality of bare polylactide-co-glycolide (PLGA) nanoparticles is limited to drug depot or drug solubilization in their hard cores. They have inherent weaknesses as a drug-delivery system. For instance, when administered intravenously, the nanoparticles undergo rapid clearance from systemic circulation before reaching the site of action. Furthermore, plain PLGA nanoparticles cannot distinguish between different cell types. Recent research shows that surface functionalization of nanoparticles and development of new nanoparticulate dosage forms help overcome these delivery challenges and improve in vivo performance. Immense research efforts have propelled the development of diverse functional PLGA-based nanoparticulate delivery systems. Representative examples include PEGylated micelles/nanoparticles (PEG, polyethylene glycol), polyplexes, polymersomes, core-shell–type lipid-PLGA hybrids, cell-PLGA hybrids, receptor-specific ligand-PLGA conjugates, and theranostics. Each PLGA-based nanoparticulate dosage form has specific features that distinguish it from other nanoparticulate systems. This review focuses on fundamental concepts and practices that are used in the development of various functional nanoparticulate dosage forms. We describe how the attributes of these functional nanoparticulate forms might contribute to achievement of desired therapeutic effects that are not attainable using conventional therapies. Functional PLGA-based nanoparticulate systems are expected to deliver chemotherapeutic, diagnostic, and imaging agents in a highly selective and effective manner. PMID:23459088

  13. Transferrin-modified PLGA nanoparticles significantly increase the cytotoxicity of paclitaxel in bladder cancer cells by increasing intracellular retention

    NASA Astrophysics Data System (ADS)

    Jin, Shihua; Zhang, Yi; Yu, Chengfan; Wang, Gang; Zhang, Zhihong; Li, Ningchen; Na, Yanqun

    2014-10-01

    To improve the anticancer effects of paclitaxel (Tax) on bladder cancer, transferrin-modified and unmodified poly( d,l lactide- co-glycolide) nanoparticles (NPs) were generated to deliver Tax. The characteristics of the NPs and the drug-release profiles were evaluated. The cytotoxicity levels of blank NPs and Tax-loaded NPs in the bladder cancer cell lines MBT-2, J-82, and TCC Sup were determined. The uptakes and retentions of the NPs by the cell lines and the intracellular distribution of the NPs were also studied. The results showed similar NPs characteristics and drug-release profiles for NPs with and without transferrin modification. The sizes of NPs with and without transferrin modification were 206 and 278 nm, respectively; the Z-potentials were -23.5 and -24.3 mV, respectively; the drug loadings were 6.5 and 6.7 % w/w, respectively. No cytotoxicity was observed in the bladder cancer cells exposed to blank NPs. Both types of Tax-loaded NPs, however, had significantly higher cytotoxicity levels compared with the Tax solution in the bladder cancer cells. The transferrin-modified, Tax-loaded NPs were significantly more cytotoxic than the Tax-loaded NPs without modification in the MBT-2 and TCC Sup cells. There were no significant differences in NP uptakes between transferrin-modified and unmodified NPs in any of the three studied bladder cancer cell lines; however, the retentions of the modified NPs were significantly higher in the MBT-2 and TCC Sup cells. These findings suggest that NPs can significantly improve the anticancer effect of Tax in bladder cells. Furthermore, transferrin-modified NPs can improve the anticancer effect by increasing intracellular retention and not by increasing uptake. The transferrin-modified NPs are promising drug delivery vehicle for bladder cancer treatment.

  14. Synthesis of gold nanoparticles using various amino acids.

    PubMed

    Maruyama, Tatsuo; Fujimoto, Yuhei; Maekawa, Tetsuya

    2015-06-01

    Gold nanoparticles (4-7nm) were synthesized from tetraauric acid using various amino acids as reducing and capping agents. The gold nanoparticles were produced from the incubation of a AuCl4(-) solution with an amino acid at 80°C for 20min. Among the twenty amino acids tested, several amino acids produced gold nanoparticles. The color of the nanoparticle solutions varied with the amino acids used for the reduction. We adopted l-histidine as a reducing agent and investigated the effects of the synthesis conditions on the gold nanoparticles. The His and AuCl4(-) concentrations affected the size of the gold nanoparticles and their aggregates. The pH of the reaction solution also affected the reaction yields and the shape of the gold nanoparticles.

  15. Mesenchymal stem cells attenuated PLGA-induced inflammatory responses by inhibiting host DC maturation and function.

    PubMed

    Zhu, Heng; Yang, Fei; Tang, Bo; Li, Xi-Mei; Chu, Ya-Nan; Liu, Yuan-Lin; Wang, Shen-Guo; Wu, De-Cheng; Zhang, Yi

    2015-01-01

    The poly lactic-co-glycolic acid (PLGA) bio-scaffold is a biodegradable scaffold commonly used for tissue repair. However, implanted PLGA scaffolds usually cause serious inflammatory responses around grafts. To improve PLGA scaffold-based tissue repair, it is important to control the PLGA-mediated inflammatory responses. Recent evidence indicated that PLGA induce dendritic cell (DC) maturation in vitro, which may initiate host immune responses. In the present study, we explored the modulatory effects of mesenchymal stem cells (MSC) on PLGA-induced DCs (PLGA-DC). We found that mouse MSCs inhibited PLGA-DC dendrite formation, as well as co-stimulatory molecule and pro-inflammatory factor expression. Functionally, MSC-educated PLGA-DCs promoted Th2 and regulatory T cell differentiation but suppressed Th1 and Th17 cell differentiation. Mechanistically, we determined that PLGA elicited DC maturation via inducing phosphorylation of p38/MAPK and ERK/MAPK pathway proteins in DCs. Moreover, MSCs suppressed PLGA-DCs by partially inactivating those pathways. Most importantly, we found that the MSCs were capable of suppressing DC maturation and immune function in vivo. Also, the proportion of mature DCs in the mice that received MSC-PLGA constructs greatly decreased compared with that of their PLGA-film implantation counterparts. Additionally, MSCs co-delivery increased regulatory T and Th2 cells but decreased the Th1 and Th17 cell numbers in the host spleens. Histological analysis showed that MSCs alleviated the inflammatory responses around the grafted PLGA scaffolds. In summary, our findings reveal a novel function for MSCs in suppressing PLGA-induced host inflammatory response and suggest that DCs are a new cellular target in improving PLGA scaffold-based tissue repair.

  16. Phenylboronic Acid-Mediated Tumor Targeting of Chitosan Nanoparticles

    PubMed Central

    Wang, Xin; Tang, Huang; Wang, Chongzhi; Zhang, Jialiang; Wu, Wei; Jiang, Xiqun

    2016-01-01

    The phenylboronic acid-conjugated chitosan nanoparticles were prepared by particle surface modification. The size, zeta potential and morphology of the nanoparticles were characterized by dynamic light scattering, zeta potential measurement and transmission electron microscopy. The cellular uptake, tumor penetration, biodistribution and antitumor activity of the nanoparticles were evaluated by using monolayer cell model, 3-D multicellular spheroid model and H22 tumor-bearing mice. The incorporation of phenylboronic acid group into chitosan nanoparticles impart a surface charge-reversible characteristic to the nanoparticles. In vitro evaluation using 2-D and 3-D cell models showed that phenylboronic acid-decorated nanoparticles were more easily internalized by tumor cells compared to non-decorated chitosan nanoparticles, and could deliver more drug into tumor cells due to the active targeting effect of boronic acid group. Furthermore, the phenylboronic acid-decorated nanoparticles displayed a deeper penetration and persistent accumulation in the multicellular spheroids, resulting in better inhibition growth to multicellular spheroids than non-decorated nanoparticles. Tumor penetration, drug distribution and near infrared fluorescence imaging revealed that phenylboronic acid-decorated nanoparticles could penetrate deeper and accumulate more in tumor area than non-decorated ones. In vivo antitumor examination demonstrated that the phenylboronic acid-decorated nanoparticles have superior efficacy in restricting tumor growth and prolonging the survival time of tumor-bearing mice than free drug and drug-loaded chitosan nanoparticles. PMID:27375786

  17. PLGA-loaded nanomedicines in melanoma treatment: Future prospect for efficient drug delivery

    PubMed Central

    Das, Sreemanti; Khuda-Bukhsh, Anisur Rahman

    2016-01-01

    Current treatment methods for melanoma have some limitations such as less target-specific action, severe side effects and resistance to drugs. Significant progress has been made in exploring novel drug delivery systems based on suitable biochemical mechanisms using nanoparticles ranging from 10 to 400 nm for drug delivery and imaging, utilizing their enhanced penetration and retention properties. Poly-lactide-co-glycolide (PLGA), a copolymer of poly-lactic acid and poly-glycolic acid, provides an ideally suited performance-based design for better penetration into skin cells, thereby having a greater potential for the treatment of melanoma. Moreover, encapsulation protects the drug from deactivation by biological reactions and interactions with biomolecules, ensuring successful delivery and bioavailability for effective treatment. Controlled and sustained delivery of drugs across the skin barrier that otherwise prohibits entry of larger molecules can be successfully made with adequately stable biocompatible nanocarriers such as PLGA for taking drugs through the small cutaneous pores permitting targeted deposition and prolonged drug action. PLGA is now being extensively used in photodynamic therapy and targeted therapy through modulation of signal proteins and drug-DNA interactions. Recent advances made on these nanomedicines and their advantages in the treatment of skin melanoma are highlighted and discussed in this review. PMID:27934796

  18. Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen.

    PubMed

    Saluja, Sandeep S; Hanlon, Douglas J; Sharp, Fiona A; Hong, Enping; Khalil, David; Robinson, Eve; Tigelaar, Robert; Fahmy, Tarek M; Edelson, Richard L

    2014-01-01

    Targeting antigen to dendritic cells (DCs) is a powerful and novel strategy for vaccination. Priming or loading DCs with antigen controls whether subsequent immunity will develop and hence whether effective vaccination can be achieved. The goal of our present work was to increase the potency of DC-based antitumor vaccines by overcoming inherent limitations associated with antigen stability and cross-presentation. Nanoparticles prepared from the biodegradable polymer poly(lactic-co-glycolic acid) have been extensively used in clinical settings for drug delivery and are currently the subject of intensive investigation as antigen delivery vehicles for vaccine applications. Here we describe a nanoparticulate delivery system with the ability to simultaneously carry a high density of protein-based antigen while displaying a DC targeting ligand on its surface. Utilizing a targeting motif specific for the DC-associated surface ligand DEC-205, we show that targeted nanoparticles encapsulating a MART-127-35 peptide are both internalized and cross-presented with significantly higher efficiency than isotype control-coated nanoparticles in human cells. In addition, the DEC-205-labeled nanoparticles rapidly escape from the DC endosomal compartment and do not colocalize with markers of early (EEA-1) or late endosome/lysosome (LAMP-1). This indicates that encapsulated antigens delivered by nanoparticles may have direct access to the class I cytoplasmic major histocompatibility complex loading machinery, overcoming the need for "classical" cross-presentation and facilitating heightened DC stimulation of anti-tumor CD8(+) T-cells. These results indicate that this delivery system provides a flexible and versatile methodology to deliver melanoma-associated antigen to DCs, with both high efficiency and heightened potency.

  19. Red Blood Cell Membrane-Cloaked Nanoparticles For Drug Delivery

    NASA Astrophysics Data System (ADS)

    Carpenter, Cody Westcott

    Herein we describe the development of the Red Blood Cell coated nanoparticle, RBC-NP. Purified natural erythrocyte membrane is used to coat drug-loaded poly(lacticco-glycolic acid) (PLGA). Synthetic PLGA co-polymer is biocompatible and biodegradable and has already received US FDA approval for drug-delivery and diagnostics. This work looks specifically at the retention of immunosuppressive proteins on RBC-NPs, right-sidedness of natural RBC membranes interfacing with synthetic polymer nanoparticles, sustained and retarded drug release of RBC-NPs as well as further surface modification of RBC-NPs for increased targeting of model cancer cell lines.

  20. Active targeted nanoparticles: Preparation, physicochemical characterization and in vitro cytotoxicity effect

    PubMed Central

    Heidarian, Sh.; Derakhshandeh, K.; Adibi, H.; Hosseinzadeh, L.

    2015-01-01

    In this study, the folate decorated biodegradable poly (lactide-co-glycolide) (PLGA) nanoparticles were developed for tumor targeting of anticancer agents. Due to the overexpression of the folate receptor on tumor surface, the folate has been efficiently employed as a targeting moiety for various anticancer agents to avoid their non-specific attacks on normal tissues and also to increase their cellular uptake within target cells. Folate conjugate PLGA was synthesized successfully and its chemical structure was evaluated by FTIR, DSC and 1HNMR spectroscopy. PLGA-folate nanoparticles (PLGA-Fol NPs) were prepared by nanoprecipitation method, adopting PLGA as a drug carrier, folic acid as a targeting ligand and 9-nitrocampthotecin as a model anticancer drug. The average size and encapsulation efficiency of the prepared PLGA-Fol NPs were found to be around 115 ± 12 nm and 57%, respectively. In vitro release profile indicated that nearly 85% of the drug was released in 50 h. The in vitro intracellular uptakes of PLGA-Fol NPs showed greater cytotoxicity on cancer cell lines compared to non-folate mediated carriers. PMID:26600851

  1. PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy

    PubMed Central

    Byeon, Hyeong Jun; Kim, Insoo; Choi, Ji Su; Lee, Eun Seong; Shin, Beom Soo; Youn, Yu Seok

    2015-01-01

    The aim of the current study was to investigate the antitumor potential of poly (D,L-lactic-co-glycolic acid) microspheres (PLGA MSs) containing polyethylene glycol (PEG)-conjugated (PEGylated) tumor necrosis factor–related apoptosis-inducing ligand (PEG-TRAIL). PEG-TRAIL PLGA MSs were prepared by using a water-in-oil-in-water double-emulsion method, and the apoptotic activities of supernatants released from the PLGA MSs at days 1, 3, and 7 were examined. The antitumor effect caused by PEG-TRAIL PLGA MSs was evaluated in pancreatic Mia Paca-2 cell-xenografted mice. PEG-TRAIL PLGA MS was found to be spherical and 14.4±1.06 μm in size, and its encapsulation efficiency was significantly greater than that of TRAIL MS (85.7%±4.1% vs 43.3%±10.9%, respectively). The PLGA MS gradually released PEG-TRAIL for 14 days, and the released PEG-TRAIL was shown to have clear apoptotic activity in Mia Paca-2 cells, whereas TRAIL released after 1 day had a negligible activity. Finally, PEG-TRAIL PLGA MS displayed remarkably greater antitumor efficacy than blank or TRAIL PLGA MS in Mia Paca-2 cell-xenografted mice in terms of tumor volume and weight, apparently due to increased stability and well-retained apoptotic activity of PEG-TRAIL in PLGA MS. We believe that this PLGA MS system, combined with PEG-TRAIL, should be considered a promising candidate for treating pancreatic cancer. PMID:25632232

  2. PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy.

    PubMed

    Byeon, Hyeong Jun; Kim, Insoo; Choi, Ji Su; Lee, Eun Seong; Shin, Beom Soo; Youn, Yu Seok

    2015-01-01

    The aim of the current study was to investigate the antitumor potential of poly (D,L-lactic-co-glycolic acid) microspheres (PLGA MSs) containing polyethylene glycol (PEG)-conjugated (PEGylated) tumor necrosis factor-related apoptosis-inducing ligand (PEG-TRAIL). PEG-TRAIL PLGA MSs were prepared by using a water-in-oil-in-water double-emulsion method, and the apoptotic activities of supernatants released from the PLGA MSs at days 1, 3, and 7 were examined. The antitumor effect caused by PEG-TRAIL PLGA MSs was evaluated in pancreatic Mia Paca-2 cell-xenografted mice. PEG-TRAIL PLGA MS was found to be spherical and 14.4±1.06 μm in size, and its encapsulation efficiency was significantly greater than that of TRAIL MS (85.7%±4.1% vs 43.3%±10.9%, respectively). The PLGA MS gradually released PEG-TRAIL for 14 days, and the released PEG-TRAIL was shown to have clear apoptotic activity in Mia Paca-2 cells, whereas TRAIL released after 1 day had a negligible activity. Finally, PEG-TRAIL PLGA MS displayed remarkably greater antitumor efficacy than blank or TRAIL PLGA MS in Mia Paca-2 cell-xenografted mice in terms of tumor volume and weight, apparently due to increased stability and well-retained apoptotic activity of PEG-TRAIL in PLGA MS. We believe that this PLGA MS system, combined with PEG-TRAIL, should be considered a promising candidate for treating pancreatic cancer.

  3. Preparation and Characterization of Polymeric Nanoparticles: An Interdisciplinary Experiment

    ERIC Educational Resources Information Center

    Ramalho, Maria J.; Pereira, M. Carmo

    2016-01-01

    In this work, a laboratory experiment to introduce graduate students to nanotechnology is described. Students prepared poly(lactic-"co"-glycolic acid) (PLGA) nanoparticles using two different synthesis procedures, a single and a double emulsion-solvent evaporation method. The students also performed a physicochemical characterization of…

  4. [Experimental study on application recombinant human bone morphogenetic protein 2(rhBMP-2)/poly-lactide-co-glycolic acid (PLGA)/fibrin sealant(FS) on repair of rabbit radial bone defect].

    PubMed

    Fan, Zhongkai; Cao, Yang; Zhang, Zhe; Zhang, Mingchao; Lu, Wei; Tang, Lei; Yao, Qi; Lu, Gang

    2012-10-01

    This paper is aimed to investigate the repair of rabbit radial bone defect by the recombinant human bone morphogenetic protein 2/poly-lactideco-glycolic acid microsphere with fibrin sealant (rhBMP-2/PLGA/FS). The radial bone defect models were prepared using New Zealand white rabbits, which were randomly divided into 3 groups, experiment group which were injected with eMP-2/PLGA/FS at bone defect location, control group which were injected with FS at bone defect location, and blank control group without treatment. The ability of repairing bone defect was evaluated with X-ray radiograph. Bone mineral density in the defect regions was analysed using the level of ossification. The osteogenetic ability of repairing bone defect, the degradation of the material, the morphologic change and the bone formation were assessed by HE staining and Masson staining. The result showed that rhBMP-2/PLGA/FS had overwhelming superiority in the osteogenetic ability and quality of bone defect over the control group, and it could promote the repair of bone defect and could especially repair the radial bone defect of rabbit well. It may be a promising and efficient synthetic bone graft.

  5. Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins.

    PubMed

    Dyawanapelly, Sathish; Koli, Uday; Dharamdasani, Vimisha; Jain, Ratnesh; Dandekar, Prajakta

    2016-08-01

    The main aim of the present study was to compare mucoadhesion and cellular uptake efficiency of chitosan (CS) and chitosan oligosaccharide (COS) surface-modified polymer nanoparticles (NPs) for mucosal delivery of proteins. We have developed poly (D, L-lactide-co-glycolide) (PLGA) NPs, surface-modified COS-PLGA NPs and CS-PLGA NPs, by using double emulsion solvent evaporation method, for encapsulating bovine serum albumin (BSA) as a model protein. Surface modification of NPs was confirmed using physicochemical characterization methods such as particle size and zeta potential, SEM, TEM and FTIR analysis. Both surface-modified PLGA NPs displayed a slow release of protein compared to PLGA NPs. Furthermore, we have explored the mucoadhesive property of COS as a material for modifying the surface of polymeric NPs. During in vitro mucoadhesion test, positively charged COS-PLGA NPs and CS-PLGA NPs exhibited enhanced mucoadhesion, compared to negatively charged PLGA NPs. This interaction was anticipated to improve the cell interaction and uptake of NPs, which is an important requirement for mucosal delivery of proteins. All nanoformulations were found to be safe for cellular delivery when evaluated in A549 cells. Moreover, intracellular uptake behaviour of FITC-BSA loaded NPs was extensively investigated by confocal laser scanning microscopy and flow cytometry. As we hypothesized, positively charged COS-PLGA NPs and CS-PLGA NPs displayed enhanced intracellular uptake compared to negatively charged PLGA NPs. Our results demonstrated that CS- and COS-modified polymer NPs could be promising carriers for proteins, drugs and nucleic acids via nasal, oral, buccal, ocular and vaginal mucosal routes.

  6. The antimicrobial and osteoinductive properties of silver nanoparticle/poly (DL-lactic-co-glycolic acid)-coated stainless steel.

    PubMed

    Liu, Yi; Zheng, Zhong; Zara, Janette N; Hsu, Chingyun; Soofer, Donnalisa E; Lee, Kevin S; Siu, Ronald K; Miller, Lloyd S; Zhang, Xinli; Carpenter, Doug; Wang, Chunling; Ting, Kang; Soo, Chia

    2012-12-01

    Implant-associated bacterial infections are one of the most serious complications in orthopedic surgery. Treatment of these infections often requires multiple operations, device removal, long-term systemic antibiotics, and extended rehabilitation, and is frequently ineffective, leading to worse clinical outcomes and increased financial costs. In this study, we evaluated silver nanoparticle/poly(DL-lactic-co-glycolic acid) (PLGA)-coated stainless steel alloy(SNPSA) as a potential antimicrobial implant material. We found that SNPSA exhibited strong antibacterial activity in vitro and ex vivo, and promoted MC3T3-E1 pre-osteoblasts proliferation and maturation in vitro. Furthermore, SNPSA implants induced osteogenesis while suppressing bacterial survival in contaminated rat femoral canals. Our results indicate that SNPSA has simultaneous antimicrobial and osteoinductive properties that make it a promising therapeutic material in orthopedic surgery.

  7. Polypyrrole-Coated Electrospun PLGA Nanofibers for Neural Tissue Applications

    PubMed Central

    Lee, Jae Young; Bashur, Chris A.; Goldstein, Aaron S.; Schmidt, Christine E.

    2009-01-01

    Electrospinning is a promising approach to create nanofiber structures that are capable of supporting adhesion and guiding extension of neurons for nerve regeneration. Concurrently, electrical stimulation of neurons in the absence of topographical features also has been shown to guide axonal extension. Therefore, the goal of this study was to form electrically conductive nanofiber structures and to examine the combined effect of nanofiber structures and electrical stimulation. Conductive meshes were produced by growing polypyrrole (PPy) on random and aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, as confirmed by scanning electron micrographs and X-ray photon spectroscopy. PPy-PLGA electrospun meshes supported the growth and differentiation of rat pheochromocytoma 12 (PC12) cells and hippocampal neurons comparable to non-coated PLGA control meshes, suggesting that PPy-PLGA may be suitable as conductive nanofibers for neuronal tissue scaffolds. Electrical stimulation studies showed that PC12 cells, stimulated with a potential of 10 mV/cm on PPy-PLGA scaffolds, exhibited 40–50% longer neurites and 40–90% more neurite formation compared to unstimulated cells on the same scaffolds. In addition, stimulation of the cells on aligned PPy-PLGA fibers resulted in longer neurites and more neurite-bearing cells than stimulation on random PPy-PLGA fibers, suggesting a combined effect of electrical stimulation and topographical guidance and the potential use of these scaffolds for neural tissue applications. PMID:19501901

  8. Thermodynamic phase behaviour of indomethacin/PLGA formulations.

    PubMed

    Prudic, Anke; Lesniak, Anna-Katharina; Ji, Yuanhui; Sadowski, Gabriele

    2015-06-01

    In the current study, the phase behaviour of indomethacin and poly(lactic-co-glycolic acid) (PLGA) formulations was investigated as a function of the molecular weight and the copolymer composition of PLGA. The formulations were prepared by ball milling, and the phase behaviour, comprised of the glass-transition temperature of the formulations and the solubility of indomethacin in PLGA, was measured using modulated differential scanning calorimetry (mDSC). The results determined that the solubility of indomethacin in PLGA at room temperature was very low and increased with a corresponding decrease in the molecular weight of PLGA. The copolymer composition of PLGA had a minor effect on the indomethacin solubility. The effect of PLGA's molecular weight and copolymer composition on the solubility of indomethacin could be modelled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) with a high degree of accuracy when compared with the experimental data. The glass-transition temperatures had a negative deviation from the weighted mean of the glass-transition temperatures of the pure substances, which could be described by the Kwei-equation.

  9. Engineering a freestanding biomimetic cardiac patch using biodegradable poly(lactic-co-glycolic acid) (PLGA) and human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs).

    PubMed

    Chen, Yin; Wang, Junping; Shen, Bo; Chan, Camie W Y; Wang, Chaoyi; Zhao, Yihua; Chan, Ho N; Tian, Qian; Chen, Yangfan; Yao, Chunlei; Hsing, I-Ming; Li, Ronald A; Wu, Hongkai

    2015-03-01

    Microgrooved thin PLGA film (≈30 μm) is successfully fabricated on a Teflon mold, which could be readily peeled off and is used for the construction of a biomimetic cardiac patch. The contraction of it is studied with optical mapping on transmembrane action potential. Our results suggest that steady-state contraction could be easily established on it under regular electrical stimuli. Besides, the biomimetic cardiac patch recapitulates the anisotropic electrophysiological feature of native cardiac tissue and is much more refractory to premature stimuli than the random one constructed with non-grooved PLGA film, as proved by the reduced incidence of arrhythmia. Considering the good biocompatibility of PLGA as demonstrated in our study and the biodegradability of it, our biomimetic cardiac patch may find applications in the treatment of myocardial infarction. Moreover, the Teflon mold could be applied in the fabrication of various scaffolds with fine features for other tissues.

  10. Inorganic nanoparticles as nucleic acid transporters into eukaryotic cells

    NASA Astrophysics Data System (ADS)

    Amirkhanov, R. N.; Zarytova, V. F.; Zenkova, M. A.

    2017-02-01

    The review is concerned with inorganic nanoparticles (gold, titanium dioxide, silica, iron oxides, calcium phosphate) used as nucleic acid transporters into mammalian cells. Methods for the synthesis of nanoparticles and approaches to surface modification through covalent or noncovalent attachment of low- or high-molecular-weight compounds are considered. The data available from the literature on biological action of nucleic acids delivered into the cells by nanoparticles and on the effect of nanoparticles and their conjugates and complexes on the cell survival are summarized. Pathways of cellular internalization of nanoparticles and the mechanism of their excretion, as well as the ways of release of nucleic acids from their complexes with nanoparticles after the cellular uptake are described. The bibliography includes 161 references.

  11. Nanoparticle-based endodontic antimicrobial photodynamic therapy

    PubMed Central

    Pagonis, Tom C.; Chen, Judy; Fontana, Carla Raquel; Devalapally, Harikrishna; Ruggiero, Karriann; Song, Xiaoqing; Foschi, Federico; Dunham, Joshua; Skobe, Ziedonis; Yamazaki, Hajime; Kent, Ralph; Tanner, Anne C.R.; Amiji, Mansoor M.; Soukos, Nikolaos S.

    2009-01-01

    Objective To study the in vitro effects of poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the photosensitizer methylene blue (MB) and light against Enterococcus faecalis (ATCC 29212). Materials and Methods The uptake and distribution of nanoparticles in E. faecalis in suspension was investigated by transmission electron microscopy (TEM) after incubation with PLGA complexed with colloidal gold particles for 2.5, 5 and 10 minutes. E. faecalis species were sensitized in planktonic phase and in experimentally infected root canals of human extracted teeth with MB-loaded nanoparticles for 10 minutes followed by exposure to red light at 665 nm. Results The nanoparticles were found to be concentrated mainly on the cell walls of microorganisms at all three time points. The synergism of light and MB-loaded nanoparticles led to approximately 2 and 1 log10 reduction of colony-forming units in planktonic phase and root canals, respectively. In both cases, mean log10 CFU levels were significantly lower than controls and MB-loaded nanoparticles without light. Conclusion The utilization of PLGA nanoparticles encapsulated with photoactive drugs may be a promising adjunct in antimicrobial endodontic treatment. PMID:20113801

  12. Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer

    PubMed Central

    Yallapu, Murali M.; Khan, Sheema; Maher, Diane M.; Ebeling, Mara C.; Sundram, Vasudha; Chauhan, Neeraj; Ganju, Aditya; Balakrishna, Swati; Gupta, Brij K.; Zafar, Nadeem; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    Prostate cancer is the most commonly diagnosed cancer disease in men in the Unites States and its management remains challenge in everyday oncology practice. Thus, advanced therapeutic strategies are required to treat prostate cancer patients. Curcumin (CUR) is a promising anticancer agent for various cancer types. The objective of this study was to evaluate therapeutic potential of novel poly(lactic-co-glycolic acid)- CUR nanoparticles (PLGA-CUR NPs) for prostate cancer treatment. Our results indicate that PLGA-CUR NPs efficiently internalize in prostate cancer cells and release biologically active CUR in cytosolic compartment of cells for effective therapeutic activity. Cell proliferation (MTS), clonogenic, and Western blot analyses reveal that PLGA-CUR NPs can effectively inhibit proliferation and colony formation ability of prostate cancer cells than free CUR. PLGA-CUR NPs showed superior tumor regression compared to CUR in xenograft mice. Further investigations reveal that PLGA-CUR NPs inhibit nuclear β-catenin and AR expression in cells and in tumor xenograft tissues. It also suppresses STAT3 and AKT phosphorylation and leads to apoptosis via inhibition of key anti-apoptotic proteins, MCL-1, Bcl-xL and caused induction of PARP cleavage. Additionally, PLGA-CUR NPs significant downregulation of oncogenic miR21 and up-regulation of miR-205 was observed with PLGA-CUR NPs treatment as determined by RT-PCR and in situ hybridization analyses. A superior anti-cancer potential was attained with PSMA antibody conjugated PLGA-CUR NPs in prostate cancer cells and a significant tumor targeting of 131I labelled PSMA antibody was achieved with PLGA-CUR NPs in prostate cancer xenograft mice model. In conclusion, PLGA-CUR NPs can significantly accumulate and exhibit superior anticancer activity in prostate cancer. PMID:25028336

  13. Permanent hair dye-incorporated hyaluronic acid nanoparticles.

    PubMed

    Lee, Hye-Young; Jeong, Young-Il; Kim, Da-Hye; Choi, Ki-Choon

    2013-01-01

    We prepared p-phenylenediamine (PDA)-incorporated nanoparticles using hyaluronic acid (HA). PDA-incorporated HA nanoparticles have spherical shapes and sizes were less than 300 nm. The results of FT-IR spectra indicated that PDA-incorporated HA nanoparticles were formed by ion-complex formation between amine group of PDA and carboxyl group of HA. Furthermore, powder-X-ray diffractogram (XRD) measurement showed that intrinsic crystalline peak of PDA disappeared by formation of nanoparticle with HA at XRD measurement. These results indicated that PDA-incorporated HA nanoparticles were formed by ion-complex formation. At drug release study, the higher PDA contents induced faster release rate from nanoparticles. PDA-incorporated nanoparticles showed reduced intrinsic toxicity against HaCaT human keratinocyte cells at MTT assay and apoptosis assay. We suggest that PDA-incorporated HA nanoparticles are promising candidates for novel permanent hair dye.

  14. Polyethylene glycol-functionalized poly (Lactic Acid-co-Glycolic Acid) and graphene oxide nanoparticles induce pro-inflammatory and apoptotic responses in Candida albicans-infected vaginal epithelial cells.

    PubMed

    Wagner, R Doug; Johnson, Shemedia J; Danielsen, Zhixia Yan; Lim, Jin-Hee; Mudalige, Thilak; Linder, Sean

    2017-01-01

    Mucous-penetrating nanoparticles consisting of poly lactic acid-co-glycolic acid (PLGA)-polyethylene glycol (PEG) could improve targeting of microbicidal drugs for sexually transmitted diseases by intravaginal inoculation. Nanoparticles can induce inflammatory responses, which may exacerbate the inflammation that occurs in the vaginal tracts of women with yeast infections. This study evaluated the effects of these drug-delivery nanoparticles on VK2(E6/E7) vaginal epithelial cell proinflammatory responses to Candida albicans yeast infections. Vaginal epithelial cell monolayers were infected with C. albicans and exposed to 100 μg/ml 49.5 nm PLGA-PEG nanospheres or 20 μg/ml 1.1 x 500 nm PEG-functionalized graphene oxide (GO-PEG) sheets. The cells were assessed for changes in mRNA and protein expression of inflammation-related genes by RT-qPCR and physiological markers of cell stress using high content analysis and flow cytometry. C. albicans exposure suppressed apoptotic gene expression, but induced oxidative stress in the cells. The nanomaterials induced cytotoxicity and programmed cell death responses alone and with C. albicans. PLGA-PEG nanoparticles induced mRNA expression of apoptosis-related genes and induced poly (ADP-ribose) polymerase (PARP) cleavage, increased BAX/BCL2 ratios, and chromatin condensation indicative of apoptosis. They also induced autophagy, endoplasmic reticulum stress, and DNA damage. They caused the cells to excrete inflammatory recruitment molecules chemokine (C-X-C motif) ligand 1 (CXCL1), interleukin-1α (IL1A), interleukin-1β (IL1B), calprotectin (S100A8), and tumor necrosis factor α (TNF). GO-PEG nanoparticles induced expression of necrosis-related genes and cytotoxicity. They reduced autophagy and endoplasmic reticulum stress, and apoptotic gene expression responses. The results show that stealth nanoparticle drug-delivery vehicles may cause intracellular damage to vaginal epithelial cells by several mechanisms and that their use

  15. Polyethylene glycol-functionalized poly (Lactic Acid-co-Glycolic Acid) and graphene oxide nanoparticles induce pro-inflammatory and apoptotic responses in Candida albicans-infected vaginal epithelial cells

    PubMed Central

    Johnson, Shemedia J.; Danielsen, Zhixia Yan; Lim, Jin-Hee; Mudalige, Thilak; Linder, Sean

    2017-01-01

    Mucous-penetrating nanoparticles consisting of poly lactic acid-co-glycolic acid (PLGA)-polyethylene glycol (PEG) could improve targeting of microbicidal drugs for sexually transmitted diseases by intravaginal inoculation. Nanoparticles can induce inflammatory responses, which may exacerbate the inflammation that occurs in the vaginal tracts of women with yeast infections. This study evaluated the effects of these drug-delivery nanoparticles on VK2(E6/E7) vaginal epithelial cell proinflammatory responses to Candida albicans yeast infections. Vaginal epithelial cell monolayers were infected with C. albicans and exposed to 100 μg/ml 49.5 nm PLGA-PEG nanospheres or 20 μg/ml 1.1 x 500 nm PEG-functionalized graphene oxide (GO-PEG) sheets. The cells were assessed for changes in mRNA and protein expression of inflammation-related genes by RT-qPCR and physiological markers of cell stress using high content analysis and flow cytometry. C. albicans exposure suppressed apoptotic gene expression, but induced oxidative stress in the cells. The nanomaterials induced cytotoxicity and programmed cell death responses alone and with C. albicans. PLGA-PEG nanoparticles induced mRNA expression of apoptosis-related genes and induced poly (ADP-ribose) polymerase (PARP) cleavage, increased BAX/BCL2 ratios, and chromatin condensation indicative of apoptosis. They also induced autophagy, endoplasmic reticulum stress, and DNA damage. They caused the cells to excrete inflammatory recruitment molecules chemokine (C-X-C motif) ligand 1 (CXCL1), interleukin-1α (IL1A), interleukin-1β (IL1B), calprotectin (S100A8), and tumor necrosis factor α (TNF). GO-PEG nanoparticles induced expression of necrosis-related genes and cytotoxicity. They reduced autophagy and endoplasmic reticulum stress, and apoptotic gene expression responses. The results show that stealth nanoparticle drug-delivery vehicles may cause intracellular damage to vaginal epithelial cells by several mechanisms and that their use

  16. Synthesis and characterization of carboxylic acid functionalized silicon nanoparticles

    NASA Astrophysics Data System (ADS)

    Shaner, Ted V.

    Silicon nanoparticles are of great interest in a great number of fields. Silicon nanoparticles show great promise particularly in the field of bioimaging. Carboxylic acid functionalized silicon nanoparticles have the ability to covalently bond to biomolecules through the conjugation of the carboxylic acid to an amine functionalized biomolecule. This thesis explores the synthesis of silicon nanoparticles functionalized by both carboxylic acids and alkenes and their carboxylic acid functionality. Also discussed is the characterization of the silicon nanoparticles by the use of x-ray spectroscopy. Finally, the nature of the Si-H bond that is observed on the surface of the silicon nanoparticles will be investigated using photoassisted exciton mediated hydrosilation reactions. The silicon nanoparticles are synthesized from both carboxylic acids and alkenes. However, the lack of solubility of diacids is a significant barrier to carboxylic acid functionalization by a mixture of monoacids and diacids. A synthesis route to overcome this obstacle is to synthesize silicon nanoparticles with terminal vinyl group. This terminal vinyl group is distal to the surface of the silicon nanoparticle. The conversion of the vinyl group to a carboxylic acid is accomplished by oxidative cleavage using ozonolysis. The carboxylic acid functionalized silicon nanoparticles were then successfully conjugated to amine functionalized DNA strand through an n-hydroxy succinimide ester activation step, which promotes the formation of the amide bond. Conjugation was characterized by TEM and polyacrylamide gel electrophoresis (PAGE). The PAGE results show that the silicon nanoparticle conjugates move slower through the polyacrylamide gel, resulting in a significant separation from the nonconjugated DNA. The silicon nanoparticles were then characterized by the use of x-ray absorption near edge spectroscopy (Xanes) and x-ray photoelectron spectroscopy (XPS) to investigate the bonding and chemical

  17. 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.

  18. Surface Mechanical and Rheological Behaviors of Biocompatible Poly((D,L-lactic acid-ran-glycolic acid)-block-ethylene glycol) (PLGA-PEG) and Poly((D,L-lactic acid-ran-glycolic acid-ran-ε-caprolactone)-block-ethylene glycol) (PLGACL-PEG) Block Copolymers at the Air-Water Interface

    SciTech Connect

    Kim, Hyun Chang; Lee, Hoyoung; Khetan, Jawahar; Won, You-Yeon

    2016-02-01

    Air–water interfacial monolayers of poly((d,l-lactic acid-ran-glycolic acid)-block-ethylene glycol) (PLGA–PEG) exhibit an exponential increase in surface pressure under high monolayer compression. In order to understand the molecular origin of this behavior, a combined experimental and theoretical investigation (including surface pressure–area isotherm, X-ray reflectivity (XR) and interfacial rheological measurements, and a self-consistent field (SCF) theoretical analysis) was performed on air–water monolayers formed by a PLGA–PEG diblock copolymer and also by a nonglassy analogue of this diblock copolymer, poly((d,l-lactic acid-ran-glycolic acid-ran-caprolactone)-block-ethylene glycol) (PLGACL–PEG). The combined results of this study show that the two mechanisms, i.e., the glass transition of the collapsed PLGA film and the lateral repulsion of the PEG brush chains that occur simultaneously under lateral compression of the monolayer, are both responsible for the observed PLGA–PEG isotherm behavior. Upon cessation of compression, the high surface pressure of the PLGA–PEG monolayer typically relaxes over time with a stretched exponential decay, suggesting that in this diblock copolymer situation, the hydrophobic domain formed by the PLGA blocks undergoes glass transition in the high lateral compression state, analogously to the PLGA homopolymer monolayer. In the high PEG grafting density regime, the contribution of the PEG brush chains to the high monolayer surface pressure is significantly lower than what is predicted by the SCF model because of the many-body attraction among PEG segments (referred to in the literature as the “n-cluster” effects). The end-grafted PEG chains were found to be protein resistant even under the influence of the “n-cluster” effects.

  19. A blue fluorescent labeling technique utilizing micro- and nanoparticles for tracking in LIVE/DEAD® stained pathogenic biofilms of Staphylococcus aureus and Burkholderia cepacia.

    PubMed

    Klinger-Strobel, Mareike; Ernst, Julia; Lautenschläger, Christian; Pletz, Mathias W; Fischer, Dagmar; Makarewicz, Oliwia

    2016-01-01

    Strategies that target and treat biofilms are widely applied to bacterial cultures using popular live/dead staining techniques with mostly red or green fluorescent markers (eg, with SYTO(®) 9, propidium iodide, fluorescein). Therefore, visualizing drugs or micro- and nanoparticulate delivery systems to analyze their distribution and effects in biofilms requires a third fluorescent dye that does not interfere with the properties of the live/dead markers. The present study establishes and evaluates a model for tracking polymeric particles in fluorescently stained biological material. To this end, poly(D,L-lactide-co-glycolide) (PLGA)-based micro- and nanoparticles were used as well-established model systems, which, because of their favorable safety profiles, are expected to play important future roles with regard to drug delivery via inhalation. PLGA was covalently and stably labeled with 7-amino-4-methyl-3-coumarinylacetic acid (AMCA), after which blue fluorescent poly(ethylene glycol)-block-PLGA (PEG-PLGA) particles were prepared using a mixture of fluorescent AMCA-PLGA and PEG-PLGA. Because chitosan is known to reduce negative surface charge, blue fluorescent PEG-PLGA-particles with chitosan were also prepared. These micro- and nanoparticles were physicochemically characterized and could be clearly distinguished from live/dead stained bacteria in biofilms using confocal laser scanning microscopy.

  20. A blue fluorescent labeling technique utilizing micro- and nanoparticles for tracking in LIVE/DEAD® stained pathogenic biofilms of Staphylococcus aureus and Burkholderia cepacia

    PubMed Central

    Klinger-Strobel, Mareike; Ernst, Julia; Lautenschläger, Christian; Pletz, Mathias W; Fischer, Dagmar; Makarewicz, Oliwia

    2016-01-01

    Strategies that target and treat biofilms are widely applied to bacterial cultures using popular live/dead staining techniques with mostly red or green fluorescent markers (eg, with SYTO® 9, propidium iodide, fluorescein). Therefore, visualizing drugs or micro- and nanoparticulate delivery systems to analyze their distribution and effects in biofilms requires a third fluorescent dye that does not interfere with the properties of the live/dead markers. The present study establishes and evaluates a model for tracking polymeric particles in fluorescently stained biological material. To this end, poly(d,l-lactide-co-glycolide) (PLGA)-based micro- and nanoparticles were used as well-established model systems, which, because of their favorable safety profiles, are expected to play important future roles with regard to drug delivery via inhalation. PLGA was covalently and stably labeled with 7-amino-4-methyl-3-coumarinylacetic acid (AMCA), after which blue fluorescent poly(ethylene glycol)-block-PLGA (PEG-PLGA) particles were prepared using a mixture of fluorescent AMCA-PLGA and PEG-PLGA. Because chitosan is known to reduce negative surface charge, blue fluorescent PEG-PLGA-particles with chitosan were also prepared. These micro- and nanoparticles were physicochemically characterized and could be clearly distinguished from live/dead stained bacteria in biofilms using confocal laser scanning microscopy. PMID:26917959

  1. Adsorption of organic acids on TiO2 nanoparticles: effects of pH, nanoparticle size, and nanoparticle aggregation.

    PubMed

    Pettibone, John M; Cwiertny, David M; Scherer, Michelle; Grassian, Vicki H

    2008-06-01

    In this study, the adsorption of two organic acids, oxalic acid and adipic acid, on TiO2 nanoparticles was investigated at room temperature, 298 K. Solution-phase measurements were used to quantify the extent and reversibility of oxalic acid and adipic acid adsorption on anatase nanoparticles with primary particle sizes of 5 and 32 nm. At all pH values considered, there were minimal differences in measured Langmuir adsorption constants, K ads, or surface-area-normalized maximum adsorbate-surface coverages, Gamma max, between 5 and 32 nm particles. Although macroscopic differences in the reactivity of these organic acids as a function of nanoparticle size were not observed, ATR-FTIR spectroscopy showed some distinct differences in the absorption bands present for oxalic acid adsorbed on 5 nm particles compared to 32 nm particles, suggesting different adsorption sites or a different distribution of adsorption sites for oxalic acid on the 5 nm particles. These results illustrate that molecular-level differences in nanoparticle reactivity can still exist even when macroscopic differences are not observed from solution phase measurements. Our results also allowed the impact of nanoparticle aggregation on acid uptake to be assessed. It is clear that particle aggregation occurs at all pH values and that organic acids can destabilize nanoparticle suspensions. Furthermore, 5 nm particles can form larger aggregates compared to 32 nm particles under the same conditions of pH and solid concentrations. The relative reactivity of 5 and 32 nm particles as determined from Langmuir adsorption parameters did not appear to vary greatly despite differences that occur in nanoparticle aggregation for these two different size nanoparticles. Although this potentially suggests that aggregation does not impact organic acid uptake on anatase particles, these data clearly show that challenges remain in assessing the available surface area for adsorption in nanoparticle aqueous suspensions

  2. Hyaluronic acid-bound letrozole nanoparticles restore sensitivity to letrozole-resistant xenograft tumors in mice.

    PubMed

    Nair, Hareesh B; Huffman, Steven; Veerapaneni, Poornachand; Kirma, Nameer B; Binkley, Peter; Perla, Rao P; Evans, Dean B; Tekmal, Rajeshwar R

    2011-05-01

    Letrozole is a potent aromatase inhibitor and superior to other defined selective estrogen receptor modulators such as tamoxifen in treating hormone-responsive postmenopausal breast cancer patients. Patients who receive this drug may become insensitive to the effects of estrogen deprivation induced by letrozole. Letrozole has known side effects on bone metabolism due to systemic ablation of estrogen production. The purpose of this study was to examine the therapeutic efficacy of hyaluronic acid-bound letrozole nanoparticles (HA-Letr-NPs) in restoring sensitivity to letrozole-resistant (LTLT-Ca) cells. To target letrozole to LTLT-Ca cells, hyaluronic acid-bound letrozole nanoparticles were prepared by nanoprecipitation using biodegradable PLGA-PEG co-polymer. Binding specificity of HA to CD44 on the cell surface was analyzed in vitro using FITC-CD44 Ab and CD44 siRNA by flow cytometry. Effects on in vitro cytotoxicity and aromatase enzymatic activity of HA-Letr-NPs were performed in MCF-7 breast cancer cells, MCF-7 cells over-expressing aromatase (MCF-7/Aro), and LTLT-Ca cells resistant to letrozole. Preclinical efficacy of HA-Letr-NPs was examined in mice using LTLT-Ca xenograft tumors. HA-Letr-NPs were restricted to a maximum size of 100 nm. The in vitro drug release assay showed that the highest released concentration of letrozole occurred after 23 hours at 37 degrees C in phosphate-buffered saline. HA-Letr-NPs on MCF-7/Aro and LTLT-Ca cells showed an IC50 of 2 microM and 5 microM, respectively. HA-Letr-NPs were more efficacious in inhibiting tumor growth, reducing in vitro cellular and in vivo tumor aromatase enzyme activity more than the corresponding Letr-NPs or letrozole. HA-Letr-NPs restored and maintained a prolonged sensitivity and targeted delivery of letrozole in letrozole-resistant tumors in vivo.

  3. Muscle regeneration by adipose tissue-derived adult stem cells attached to injectable PLGA spheres.

    PubMed

    Kim, MiJung; Choi, Yu Suk; Yang, Seung Hye; Hong, Hea-Nam; Cho, Sung-Woo; Cha, Sang Myun; Pak, Jhang Ho; Kim, Chan Wha; Kwon, Seog Woon; Park, Chan Jeoung

    2006-09-22

    The [corrected] use of adult stem cells for cell-based tissue engineering and regeneration strategies represents a promising approach for skeletal muscle repair. We have evaluated the combination of adipose tissue-derived adult stem cells (ADSCs) obtained from autologous liposuction and injectable poly(lactic-co-glycolic acid) (PLGA) spheres for muscle regeneration. ADSCs attached to PLGA spheres and PLGA spheres alone were cultured in myogenic medium for 21 days and injected subcutaneously into the necks of nude mice. After 30 and 60 days, the mice were sacrificed, and newly formed tissues were analyzed by immunostaining, H and E staining, and RT-PCR. We found that ADSCs attached to PLGA spheres, but not PLGA spheres alone, were able to generate muscle tissue. These findings suggest that ADSCs and PLGA spheres are useful materials for muscle tissue engineering and that their combination can be used in clinical settings for muscle regeneration.

  4. Arginine-Glycine-Aspartic Acid-Modified Lipid-Polymer Hybrid Nanoparticles for Docetaxel Delivery in Glioblastoma Multiforme.

    PubMed

    Shi, Kairong; Zhou, Jin; Zhang, Qianyu; Gao, Huile; Liu, Yayuan; Zong, Taili; He, Qin

    2015-03-01

    Hybrid nanoparticles consisting of lipids and the biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), were developed for the targeted delivery of the anticancer drug, docetaxel. Transmission electron microscopic observations confirmed the presence of a lipid coating over the polymeric core. Using coumarin-6 as a fluorescent probe, the uptake efficacy of RGD conjugated lipid coated nanoparticles (RGD-L-P) by C6 cells was increased significantly, compared with that of lipid-polymer hybrid nanoparticles (L-P; 2.5-fold higher) or PLGA-nanoparticles (PLGA-P; 1.76-fold higher). The superior tumor spheroid penetration of RGD-L-P indicated that RGD-L-P could target effectively and specifically to C6 cells overexpressing integrin α(v)β3. The anti-proliferative activity of docetaxel-loaded RGD-L-P against C6 cells was increased 2.69- and 4.13-fold compared with L-P and PLGA-P, respectively. Regarding biodistribution, the strongest brain-localized fluorescence signals were detected in glioblastoma multiforme (GBM)-bearing rats treated with 1,10-Dioctadecyl-3,3,30,30-tetramethylindotricarb-ocyanine iodide (DiR)-loaded RGD-L-P, compared to rats treated with DiR-loaded L-P or PLGA-P. The median survival time of GBM-bearing rats treated with docetaxel-loaded RGD-L-P was 57 days, a fold increase of 1.43, 1.78, 3.35, and 3.56 compared with animals given L-P (P < 0.05), PLGA-P (P < 0.05), Taxotere (P < 0.01) and saline (P < 0.01), respectively. Collectively, these results support RGD-L-P as a promising drug delivery system for the specific targeting and the treatment of GBM.

  5. Complexation With Human Serum Albumin Facilitates Sustained Release of Morin From Polylactic-Co-Glycolic Acid Nanoparticles.

    PubMed

    Ghosh, Pooja; Patwari, Jayita; Dasgupta, Swagata

    2017-03-02

    Understanding the interaction of proteins with nanoparticles has become an important area of research in biomedical and pharmaceutical fields. Morin is a flavonol which shows several properties including antioxidant, anticancer, and anti-inflammatory activities. However, the major limitation is its poor aqueous solubility. Therefore, morin-loaded polylactic-co-glycolic acid (PLGA) nanoparticles (MPNPs) were prepared to improve the solubility of morin. The resulting MPNPs were characterized by spectroscopic and microscopic techniques. The nanoparticles were spherical with an average size of 237 ± 17 nm. UV-visible, fluorescence, and circular dichroism (CD) spectroscopy were employed to study the interaction of the MPNPs with human serum albumin (HSA). Our study revealed that a static fluorescence quenching mechanism was involved in the interaction between HSA and MPNPs. Hydrophobic interactions also play an important role in stabilizing the HSA-MPNP complex. CD results suggest that there is an alteration of the secondary structure of HSA in the presence of MPNPs. MPNPs exhibit antioxidant properties which are supported by the DPPH assay. We have further checked the effect of HSA on the antioxidant property of morin and MPNPs. HSA binding with MPNPs was also found to influence the in vitro release property of morin from MPNPs wherein a delayed release response is observed.

  6. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations

    PubMed Central

    Makita-Chingombe, Faithful; Kutscher, Hilliard L.; DiTursi, Sara L.; Morse, Gene D.; Maponga, Charles C.

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and −20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1. PMID:27190651

  7. Formulations for modulation of protein release from large-size PLGA microparticles for tissue engineering.

    PubMed

    Qodratnama, Roozbeh; Serino, Lorenzo Pio; Cox, Helen C; Qutachi, Omar; White, Lisa J

    2015-02-01

    In this study we present an approach to pre-program lysozyme release from large size (100-300 μm) poly(DL-lactic acid-co-glycolic acid) (PLGA) microparticles. This approach involved blending in-house synthesized triblock copolymers with a PLGA 85:15. In this work it is demonstrated that the lysozyme release rate and the total release are related to the mass of triblock copolymer present in polymer formulation. Two triblock copolymers (PLGA-PEG1500-PLGA and PLGA-PEG1000-PLGA) were synthesized and used in this study. In a like-for-like comparison, these two triblock copolymers appeared to have similar effects on the release of lysozyme. It was shown that blending resulted in the increase of the total lysozyme release and shortened the release period (70% release within 30 days). These results demonstrated that blending PLGA-PEG-PLGA triblock copolymer with PLGA 85:15 can be used as a method to pre-program protein release from microparticles. These microparticles with modulated protein release properties may be used to create microparticle-based tissue engineering constructs with pre-programmed release properties.

  8. 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

  9. 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.

  10. Thermo-sensitive hydrogel PLGA-PEG-PLGA as a vaccine delivery system for intramuscular immunization.

    PubMed

    Wang, Xiaoyan; Zhang, Yu; Xue, Wei; Wang, Hong; Qiu, Xiaozhong; Liu, Zonghua

    2016-11-25

    In this work, we explored the potential of thermo-sensitive PLGA-PEG-PLGA with sol-gel transition temperature around 32℃ as an intramuscular vaccine delivery system by using ovalbumin as a model antigen. First, in vitro release test showed that the PLGA-PEG-PLGA-deriving hydrogels could release ovalbumin in vitro in a more sustainable way. From fluorescence living imaging, 50-200 mg/mL of PLGA-PEG-PLGA formulations could release antigen in a sustainable manner in vivo, suggesting that the PLGA-PEG-PLGA hydrogel worked as an antigen-depot. Further, the sustainable antigen release from the PLGA-PEG-PLGA hydrogels increased antigen availability in the spleens of the immunized mice. The intramuscular immunization results showed that 50-200 mg/mL of PLGA-PEG-PLGA formulations promoted significantly more potent antigen-specific IgG immune response. In addition, 200 mg/mL of PLGA-PEG-PLGA formulation significantly enhanced the secretion of both Th1 and Th2 cytokines. From in vitro splenocyte proliferation assay, 50-200 mg/mL of PLGA-PEG-PLGA formulations all initiated significantly higher splenocyte activation. These results indicate that the thermo-sensitive and injectable PLGA-PEG-PLGA hydrogels (particularly, 200 mg/mL of PLGA-PEG-PLGA-based hydrogel) own promising potential as an intramuscular vaccine delivery system.

  11. Dimensionality reduction, and function approximation of poly(lactic-co-glycolic acid) micro- and nanoparticle dissolution rate

    PubMed Central

    Ojha, Varun Kumar; Jackowski, Konrad; Abraham, Ajith; Snášel, Václav

    2015-01-01

    Prediction of poly(lactic-co-glycolic acid) (PLGA) micro- and nanoparticles’ dissolution rates plays a significant role in pharmaceutical and medical industries. The prediction of PLGA dissolution rate is crucial for drug manufacturing. Therefore, a model that predicts the PLGA dissolution rate could be beneficial. PLGA dissolution is influenced by numerous factors (features), and counting the known features leads to a dataset with 300 features. This large number of features and high redundancy within the dataset makes the prediction task very difficult and inaccurate. In this study, dimensionality reduction techniques were applied in order to simplify the task and eliminate irrelevant and redundant features. A heterogeneous pool of several regression algorithms were independently tested and evaluated. In addition, several ensemble methods were tested in order to improve the accuracy of prediction. The empirical results revealed that the proposed evolutionary weighted ensemble method offered the lowest margin of error and significantly outperformed the individual algorithms and the other ensemble techniques. PMID:25709436

  12. Biodegradable polymeric nanoparticles containing gold nanoparticles and Paclitaxel for cancer imaging and drug delivery using photoacoustic methods

    PubMed Central

    Wang, Yanjie; Strohm, Eric M.; Sun, Yang; Wang, Zhaoxia; Zheng, Yuanyi; Wang, Zhigang; Kolios, Michael C.

    2016-01-01

    In this study, optical-triggered multifunctional theranostic agents for photoacoustic/fluorescent imaging and cancer therapy have been developed. This system consists of a perfluorohexane liquid and gold nanoparticles (GNPs) in the core, stabilized by a Poly (lactide-co-glycolic acid) (PLGA) polymer shell. When cancer cells containing PLGA-GNPs were exposed to laser pulses, cell viability decreased due to the vaporization of the particles in and around the cells. The particle chemo drug loading and delivery capacity was also investigated in vitro experiments. These particles show potential as photoacoustic imaging and therapy agents for future clinical translation in cancer therapy. PMID:27867720

  13. Preparation and in vitro-in vivo evaluation of salmon calcitonin-loaded polymeric nanoparticles.

    PubMed

    Glowka, Eliza; Sapin-Minet, Anne; Leroy, Pierre; Lulek, Janina; Maincent, Philippe

    2010-01-01

    The aim of the study was to develop and characterize polymeric nanoparticles as a sustained release system for salmon calcitonin (sCT). Nanoparticles were prepared by a double emulsion solvent evaporation method using Eudragit RS and two types of a biodegradable poly(lactic-co-glycolic) copolymer (PLGA). It was demonstrated that sCT was incorporated into nanoparticles with encapsulation efficiencies in the range 69-83%. In vitro release studies, unconventionally conducted in 5% acetic acid, showed great differences in sCT release time profiles. Nanoparticles with fast release profile (Eudragit RS, PLGA/Eudragit RS) released 80-100% of the encapsulated drug within a few hours. In contrast, the sCT release from pure PLGA nanoparticles was very slow, incomplete and reached only 20% after 4 weeks. In vivo study, conducted in Wistar rats, proved that elevated serum sCT levels could be sustained for 3 days after subcutaneous administration of PLGA nanoparticles and the achieved bioavailability was increased compared to sCT solution.

  14. Enhanced formic acid oxidation on Cu-Pd nanoparticles

    NASA Astrophysics Data System (ADS)

    Dai, Lin; Zou, Shouzhong

    Developing catalysts with high activity and high resistance to surface poisoning remains a challenge in direct formic acid fuel cell research. In this work, copper-palladium nanoparticles were formed through a galvanic replacement process. After electrochemically selective dissolution of surface Cu, Pd-enriched Cu-Pd nanoparticles were formed. These particles exhibit much higher formic acid oxidation activities than that on pure Pd nanoparticles, and they are much more resistant to the surface poisoning. Possible mechanisms of catalytic activity enhancement are briefly discussed.

  15. Periodontal tissue regeneration by transplantation of rat adipose-derived stromal cells in combination with PLGA-based solid scaffolds.

    PubMed

    Akita, Daisuke; Morokuma, Masakazu; Saito, Yoko; Yamanaka, Katsuyuki; Akiyama, Yuko; Sato, Momoko; Mashimo, Takayuki; Toriumi, Taku; Arai, Yoshinori; Kaneko, Tadashi; Tsukimura, Naoki; Isokawa, Keitaro; Ishigami, Tomohiko; Honda, Masaki J

    2014-01-01

    Regeneration of damaged periodontium is challenging due to its multi-tissue composition. Mesenchymalstem cell-based approaches using adipose-derived stromal cells (ASCs) may contribute to periodontal reconstruction, particularly when combined with the use of scaffolds to maintain a space for new tissue growth. The aim of this study was to assess the regenerative potential of ASCs derived from inbred or outbred rats in combination with novel solid scaffolds composed of PLGA (Poly D,L-lactic-co-glycolic acid) (PLGA-scaffolds). Cultured ASCs seeded onto PLGA scaffolds (ASCs/PLGA) or PLGA-scaffolds (PLGA) alone were transplanted into periodontal fenestration defects created in F344 or Sprague Dawley (SD) rats. Micro-CT analysis showed a significantly higher percentage of bone growth in the ASCs/PLGA groups compared with the PLGA-alone groups at five weeks after surgery. Similarly, histomorphometric analysis demonstrated thicker growth of periodontal ligament and cementum layers in the ASCs/PLGA-groups compared with the PLGA-alone groups. In addition, transplanted DiI-labeled ASCs were observed in the periodontal regenerative sites. The present investigation demonstrated the marked ability of ASCs in combination with PLGA scaffolds to repair periodontal defects.

  16. Mechanical properties of dispersed ceramic nanoparticles in polymer composites for orthopedic applications

    PubMed Central

    Liu, Huinan; Webster, Thomas J

    2010-01-01

    Ceramic/polymer composites have been considered as third-generation orthopedic biomaterials due to their ability to closely match properties (such as surface, chemistry, biological, and mechanical) of natural bone. It has already been shown that the addition of nanophase compared with conventional (or micron-scale) ceramics to polymers enhances bone cell functions. However, in order to fully take advantage of the promising nanometer size effects that nanoceramics can provide when added to polymers, it is critical to uniformly disperse them in a polymer matrix. This is critical since ceramic nanoparticles inherently have a strong tendency to form larger agglomerates in a polymer matrix which may compromise their properties. Therefore, in this study, model ceramic nanoparticles, specifically titania and hydroxyapatite (HA), were dispersed in a model polymer (PLGA, poly-lactic-co-glycolic acid) using high-power ultrasonic energy. The mechanical properties of the resulting PLGA composites with well-dispersed ceramic (either titania or HA) nanoparticles were investigated and compared with composites with agglomerated ceramic nanoparticles. Results demonstrated that well-dispersed ceramic nanoparticles (titania or HA) in PLGA improved mechanical properties compared with agglomerated ceramic nanoparticles even though the weight percentage of the ceramics was the same. Specifically, well-dispersed nanoceramics in PLGA enhanced the tensile modulus, tensile strength at yield, ultimate tensile strength, and compressive modulus compared with the more agglomerated nanoceramics in PLGA. In summary, supplemented by previous studies that demonstrated greater osteoblast (bone-forming cell) functions on well-dispersed nanophase ceramics in polymers, the present study demonstrated that the combination of PLGA with well-dispersed nanoceramics enhanced mechanical properties necessary for load-bearing orthopedic/dental applications. PMID:20463945

  17. Preparation and bactericide activity of gallic acid stabilized gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Moreno-Álvarez, S. A.; Martínez-Castañón, G. A.; Niño-Martínez, N.; Reyes-Macías, J. F.; Patiño-Marín, N.; Loyola-Rodríguez, J. P.; Ruiz, Facundo

    2010-10-01

    In this work, gold nanoparticles with three different sizes (13.7, 39.4, and 76.7 nm) were prepared using a simple aqueous method with gallic acid as the reducing and stabilizing agent, the different sizes were obtained varying some experimental parameters as the pH of the reaction and the amount of the gallic acid. The prepared nanoparticles were characterized using X-ray diffraction, transmission electron microscopy, dynamic light scattering, and UV-Vis spectroscopy. Samples were identified as elemental gold and present spherical morphology, a narrow size distribution and good stabilization according to TEM and DLS results. The antibacterial activity of this gallic acid stabilized gold nanoparticles against S. mutans (the etiologic agent of dental caries) was assessed using a microdilution method obtaining a minimum inhibitory concentration of 12.31, 12.31, and 49.25 μg/mL for 13.7, 39.4, and 76.7 nm gold nanoparticles, respectively. The antibacterial assay showed that gold nanoparticles prepared in this work present a bactericide activity by a synergistic action with gallic acid. The MIC found for this nanoparticles are much lower than those reported for mixtures of gold nanoparticles and antibiotics.

  18. Enhanced oral bioavailability of insulin using PLGA nanoparticles co-modified with cell-penetrating peptides and Engrailed secretion peptide (Sec).

    PubMed

    Zhu, Siqi; Chen, Shuangxi; Gao, Yuan; Guo, Feng; Li, Fengying; Xie, Baogang; Zhou, Jianliang; Zhong, Haijun

    2016-07-01

    Biodegradable polymer nanoparticle drug carriers are an attractive strategy for oral delivery of peptide and protein drugs. However, their ability to cross the intestinal epithelium membrane is largely limited. Therefore, in the present study, cell-penetrating peptides (R8, Tat, penetratin) and a secretion peptide (Sec) with N-terminal stearylation were introduced to modify nanoparticles (NPs) on the surface to improve oral bioavailability of peptide and protein drugs. In vitro studies conducted in Caco-2 cells showed the value of the apparent permeability coefficient (Papp) of the nanoparticles co-modified with Sec and penetratin (Sec-Pen-NPs) was about two-times greater than that of the nanoparticles modified with only penetratin (Pen-NPs), while the increase of transcellular transport of nanoparticles modified together with Sec and R8 (Sec-R8-NPs), or Sec and Tat (Sec-Tat-NPs), was not significant compared with nanoparticles modified with only R8 (R8-NPs) or Tat (Tat-NPs). Using insulin as the model drug, in vivo studies performed on rats indicated that compared to Pen-NPs, the relative bioavailability of insulin for Sec-Pen-NPs was 1.71-times increased after ileal segments administration, and stronger hypoglycemic effects was also observed. Therefore, the nanoparticles co-modified with penetratin and Sec could act as attractive carriers for oral delivery of insulin.

  19. Preparation and evaluations in vitro of oxaliplatin polylactic acid nanoparticles.

    PubMed

    Cui, Zhaoyuan; Sun, Yong; Liu, Xiaohong; Ju, Fang; Chen, Qian; Gao, Wen; Wei, Haitian

    2013-08-01

    The oxaliplatin nanoparticles were prepared with polylactic acid matrix, orthogonal test was applied to optimize the prescriptions, and the qualities of oxaliplatin nanoparticles were characterized by the shape, particle size, encapsulation efficiency (EE), and drug loading (DL). Oxaliplatin nanoparticle was prepared by solution replacement method. The formation of 0.25% Tween80, DMF-water 1:8 (v/v), oxaliplatin-polylactic acid 1:5 (w/w), and 20 mg/ml polylactic acid showed the suitable EE (17.4 ± 0.47%), DL (3.52 ± 0.07%). We observed the shape of oxaliplatin nanoparticles through SEM. The average size of the particles was 120.5 ± 8.7 nm, which was detected by N5 submicron particle size analyzer.

  20. Synthesis and characterization of magnetite nanoparticles coated with lauric acid

    SciTech Connect

    Mamani, J.B.; Costa-Filho, A.J.; Cornejo, D.R.; Vieira, E.D.; Gamarra, L.F.

    2013-07-15

    Understanding the process of synthesis of magnetic nanoparticles is important for its implementation in in vitro and in vivo studies. In this work we report the synthesis of magnetic nanoparticles made from ferrous oxide through coprecipitation chemical process. The nanostructured material was coated with lauric acid and dispersed in aqueous medium containing surfactant that yielded a stable colloidal suspension. The characterization of magnetic nanoparticles with distinct physico-chemical configurations is fundamental for biomedical applications. Therefore magnetic nanoparticles were characterized in terms of their morphology by means of TEM and DLS, which showed a polydispersed set of spherical nanoparticles (average diameter of ca. 9 nm) as a result of the protocol. The structural properties were characterized by using X-ray diffraction (XRD). XRD pattern showed the presence of peaks corresponding to the spinel phase of magnetite (Fe{sub 3}O{sub 4}). The relaxivities r{sub 2} and r{sub 2}* values were determined from the transverse relaxation times T{sub 2} and T{sub 2}* at 3 T. Magnetic characterization was performed using SQUID and FMR, which evidenced the superparamagnetic properties of the nanoparticles. Thermal characterization using DSC showed exothermic events associated with the oxidation of magnetite to maghemite. - Highlights: • Synthesis of magnetic nanoparticles coated with lauric acid • Characterization of magnetic nanoparticles • Morphological, structural, magnetic, calorimetric and relaxometric characterization.

  1. Poly(lactic- co-glycolic) acid nanoparticles uptake by Vitis vinifera and grapevine-pathogenic fungi

    NASA Astrophysics Data System (ADS)

    Valletta, Alessio; Chronopoulou, Laura; Palocci, Cleofe; Baldan, Barbara; Donati, Livia; Pasqua, Gabriella

    2014-12-01

    Poly(lactic- co-glycolic) acid (PLGA)-based NPs are currently considered among the most promising drug carriers, nevertheless their use in plants has never been investigated. In this work, for the first time, we demonstrated the ability of PLGA NPs to cross the plant cell wall and membrane of Vitis vinifera cell cultures and grapevine-pathogenic fungi. By means of fluorescence microscopy, we established that PLGA NPs can enter in grapevine leaf tissues through stomata openings and that they can be absorbed by the roots and transported to the shoot through vascular tissues. TEM analysis on cultured cells showed that NPs ≤ 50 nm could enter cells, while bigger ones remained attached to the cell wall. Viability tests demonstrated that PLGA NPs were not cytotoxic for V. vinifera-cultured cells. The cellular uptake of PLGA NPs by some important grapevine-pathogenic fungi has also been observed, thus suggesting that PLGA NPs could be used to deliver antifungal compounds within fungal cells. Overall the results reported suggest that such NPs may play a key role in future developments of agrobiotechnologies, as it is currently happening in biomedicine.

  2. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

    NASA Astrophysics Data System (ADS)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  3. Photo-crosslinked hyaluronic acid coated upconverting nanoparticles

    NASA Astrophysics Data System (ADS)

    Mrazek, Jiri; Kettou, Sofiane; Matuska, Vit; Svozil, Vit; Huerta-Angeles, Gloria; Pospisilova, Martina; Nesporova, Kristina; Velebny, Vladimir

    2017-02-01

    Hyaluronic acid (HA)-coated inorganic nanoparticles display enhanced interaction with the CD44 receptors which are overexpressed in many types of cancer cells. Here, we describe a modification of core-shell β-NaY0.80Yb0.18Er0.02F4@NaYF4 nanoparticles (UCNP) by HA derivative bearing photo-reactive groups. UCNP capped with oleic acid were firstly transferred to aqueous phase by an improved protocol using hydrochloric acid or lactic acid treatment. Subsequently, HA bearing furanacryloyl moieties (HA-FU) was adsorbed on the nanoparticle surface and crosslinked by UV irradiation. The crosslinking resulted in stable HA coating, and no polymer desorption was observed. As-prepared UCNP@HA-FU show a hydrodynamic diameter of about 180 nm and are colloidally stable in water and cell culture media. The cellular uptake by normal human fibroblasts and MDA MB-231 cancer cell line was investigated by upconversion luminescence imaging.

  4. Synthesis, Characterization, and Biological Evaluation of Anti-HER2 Indocyanine Green-Encapsulated PEG-Coated PLGA Nanoparticles for Targeted Phototherapy of Breast Cancer Cells

    PubMed Central

    Lee, Yu-Hsiang; Lai, Yun-Han

    2016-01-01

    Human epidermal growth factor receptor 2 (HER2)-overexpressed breast cancer is known to be more aggressive and resistant to medicinal treatment and therefore to whom an alternative therapeutics is needed. Indocyanine green (ICG) has been widely exploited in breast cancer phototherapy. However, drawbacks of accelerated degradation and short half-life (2–4 min) in blood seriously hamper its use in the clinic. To overcome these challenges, an anti-HER2 ICG-encapsulated polyethylene glycol-coated poly(lactic-co-glycolic acid) nanoparticles (HIPPNPs) were developed in this study. Through the analyses of degradation rate coefficients of ICG with and without polymeric encapsulation, the photostability of HIPPNP-entrapped ICG significantly enhanced 4 folds (P < 0.05) while its thermal stabilities at 4 and 37°C significantly enhanced 5 and 3 (P < 0.05 for each) folds, respectively, under equal lighting and/or heating treatment for 48 h. The target specificity of HIPPNPs to HER2-positive cells was demonstrated based on a 6-fold (P < 0.05) enhancement of uptake efficiency of HIPPNPs in MDA-MB-453/HER2(+) cells within 4 h as compared with that in MCF7/HER2(-) cells. Moreover, the HIPPNPs with ≤ 25 μM ICG equivalent were nontoxic to cells in the absence of light illumination, and enabled to generate similar amount of singlet oxygen and hyperthermia effect as compared with that used by free ICG upon NIR irradiation. After 808 nm-laser irradiation with intensity of 6 W/cm2 for 5 min, the viability of MDA-MB-453 cells pre-treated by HIPPNPs with ≥ 5 μM ICG equivalent for 4 h significantly reduced as compared with that treated by equal concentration of free ICG (P < 0.05) and > 90% of the cells were eradicated while the dose of HIPPNPs was increased to 25 μM ICG equivalent. In summary, the developed HIPPNPs are anticipated as a feasible tool for use in phototherapy of breast cancer cells with HER2 expression. PMID:27942034

  5. Immunization of guinea pigs with novel hepatitis B antigen as nanoparticle aggregate powders administered by the pulmonary route.

    PubMed

    Muttil, Pavan; Prego, Cecilia; Garcia-Contreras, Lucila; Pulliam, Brian; Fallon, John Kevin; Wang, Chenchen; Hickey, Anthony James; Edwards, David

    2010-09-01

    Novel nanoparticle-aggregate formulations containing recombinant hepatitis B surface antigen (rHBsAg) were administered to the lungs of guinea pigs and antibodies generated to this antigen evaluated. Preparations of dry powders of: (a) rHBsAg encapsulated within poly(lactic-co-glycolic acid) (PLGA)/polyethylene glycol (PEG) nanoparticles (antigen nanoparticles, AgN(SD)), (b) rHBsAg in a physical mixture with blank PLGA/PEG nanoparticles (antigen nanoparticle admixture (AgNA(SD)), and (c) rHBsAg encapsulated in PLGA/PEG nanoparticles plus free rHBsAg (antigen nanoparticles and free antigen), were generated by spray drying with leucine. Control groups consisted of alum with adsorbed rHBsAg (AlumAg); reconstituted suspensions of spray-dried rHBsAg-loaded PLGA/PEG nanoparticles with leucine; and rHBsAg-loaded PLGA/PEG nanoparticles (AgN). Control preparations were administered by intramuscular injection; AgN was also spray instilled into the lungs. The IgG titers were measured in the serum for 24 weeks after the initial immunization; IgA titers were measured in the bronchio-alveolar lavage fluid. While the highest titer of serum IgG antibody was observed in guinea pigs immunized with AlumAg administered by the IM route, animals immunized with powder formulations via the pulmonary route exhibited high IgA titers. In addition, guinea pigs immunized with AgNA(SD) via the pulmonary route exhibited IgG titers above 1,000 mIU/ml in the serum (IgG titers above 10 mIU/ml is considered protective). Thus, the disadvantages observed with the existing hepatitis B vaccine administered by the parenteral route may be overcome by administering them as novel dry powders to the lungs. In addition, these powders have the advantage of eliciting a high mucosal immune response in the lungs without traditional adjuvants.

  6. Understanding greater cardiomyocyte functions on aligned compared to random carbon nanofibers in PLGA.

    PubMed

    Asiri, Abdullah M; Marwani, Hadi M; Khan, Sher Bahadar; Webster, Thomas J

    2015-01-01

    Previous studies have demonstrated greater cardiomyocyte density on carbon nanofibers (CNFs) aligned (compared to randomly oriented) in poly(lactic-co-glycolic acid) (PLGA) composites. Although such studies demonstrated a closer mimicking of anisotropic electrical and mechanical properties for such aligned (compared to randomly oriented) CNFs in PLGA composites, the objective of the present in vitro study was to elucidate a deeper mechanistic understanding of how cardiomyocyte densities recognize such materials to respond more favorably. Results showed lower wettability (greater hydrophobicity) of CNFs embedded in PLGA compared to pure PLGA, thus providing evidence of selectively lower wettability in aligned CNF regions. Furthermore, the results correlated these changes in hydrophobicity with increased adsorption of fibronectin, laminin, and vitronectin (all proteins known to increase cardiomyocyte adhesion and functions) on CNFs in PLGA compared to pure PLGA, thus providing evidence of selective initial protein adsorption cues on such CNF regions to promote cardiomyocyte adhesion and growth. Lastly, results of the present in vitro study further confirmed increased cardiomyocyte functions by demonstrating greater expression of important cardiomyocyte biomarkers (such as Troponin-T, Connexin-43, and α-sarcomeric actin) when CNFs were aligned compared to randomly oriented in PLGA. In summary, this study provided evidence that cardiomyocyte functions are improved on CNFs aligned in PLGA compared to randomly oriented in PLGA since CNFs are more hydrophobic than PLGA and attract the adsorption of key proteins (fibronectin, laminin, and vironectin) that are known to promote cardiomyocyte adhesion and expression of important cardiomyocyte functions. Thus, future studies should use this knowledge to further design improved CNF:PLGA composites for numerous cardiovascular applications.

  7. Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles.

    PubMed

    Wang, Lei; Hao, Yongwei; Li, Haixia; Zhao, Yalin; Meng, Dehui; Li, Dong; Shi, Jinjin; Zhang, Hongling; Zhang, Zhenzhong; Zhang, Yun

    2015-01-01

    It is very challenging to treat brain cancer because of the blood-brain barrier (BBB) restricting therapeutic drug or gene to access the brain. In this research project, angiopep-2 (ANG) was used as a brain-targeted peptide for preparing multifunctional ANG-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which encapsulated both doxorubicin (DOX) and epidermal growth factor receptor (EGFR) siRNA, designated as ANG/PLGA/DOX/siRNA. This system could efficiently deliver DOX and siRNA into U87MG cells leading to significant cell inhibition, apoptosis and EGFR silencing in vitro. It demonstrated that this drug system was capable of penetrating the BBB in vivo, resulting in more drugs accumulation in the brain. The animal study using the brain orthotopic U87MG glioma xenograft model indicated that the ANG-targeted co-delivery of DOX and EGFR siRNA resulted in not only the prolongation of the life span of the glioma-bearing mice but also an obvious cell apoptosis in glioma tissue.

  8. Protective effects of poly(lactic-co-glycolic acid) nanoparticles loaded with erythropoietin stabilized by sodium cholate against glutamate-induced neurotoxicity.

    PubMed

    Jeong, Ji Heun; Kang, Seung Hee; Kim, Jeong Hwan; Yu, Kwang Sik; Lee, In Ho; Lee, Ye Ji; Lee, Je Hun; Lee, Nam Seob; Jeong, Young Gil; Kim, Do Kyung; Kim, Gyu Hyun; Lee, Shin Hye; Hong, Seul Ki; Han, Seung-Yun; Kang, Bo Sun

    2014-11-01

    The final aim of this study was to confirm the neuroprotective effects of recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles stabilized by sodium cholate (rhEPO-Ch-NP) and compare their effects with those of rhEPO using an in vitro model of cerebral ischemia. Glutamate-induced excitotoxic damage on SH-SY5Y cells, a human neuroblastoma cell line, with or without rhEPO-Ch-NPs was quantitatively evaluated. The rhEPO-Ch-NPs were carefully prepared using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation technique with PLGA, sodium cholate hydrate, and ethyl acetate. The rhEPO-Ch-NPs were fully characterized by both transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). In addition, significant intracellular uptake of these particles was monitored by confocal microscopy. Notably, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and nuclear changes observed by 4',6-diamidino-2-phenylindole (DAPI) staining in SH-SY5Y cells demonstrated that rhEPO-Ch-NPs were safer at any concentration investigated and rescued more neuronal cells, while preserving normocytic features against glutamate-induced excitotoxic damages compared to rhEPO.

  9. Evaluation of polylactic acid nanoparticles safety using Drosophila model.

    PubMed

    Legaz, Sophie; Exposito, Jean-Yves; Lethias, Claire; Viginier, Barbara; Terzian, Christophe; Verrier, Bernard

    2016-10-01

    Cytotoxicity of nanoparticles and their sub-lethal effect on cell behavior and cell fate are a high topic of studies in the nanomaterial field. With an explosion of nanoparticle types (size, shape, polarity, stiffness, composition, etc.), Drosophila has become an attractive animal model for high throughput analysis of these nanocarriers in the drug delivery field with applications in cancer therapy, or simply to generate a fast and complete cytotoxic study of a peculiar nanoparticle. In respect to that, we have conducted an in cellulo study of poly(lactic acid) (PLA) nanoparticle cytotoxicity, and determined that near lethal nanoparticle doses, oxidative stress as well as P53 and ATP pathways may lead to cell cycle arrest at G1, and ultimately to cell death. Neither viability nor the development of Drosophila larvae are affected by the ingestion of PLA nanoparticles at sub-lethal concentrations. Drosophila will be a useful model to study PLA and PLA-modified nanoparticle toxicity, and nanoparticle fate after ingestion.

  10. In vivo biocompatibility of the PLGA microparticles in parotid gland

    PubMed Central

    Cantín, Mario; Miranda, Patricio; Suazo Galdames, Iván; Zavando, Daniela; Arenas, Patricia; Velásquez, Luis; Vilos, Cristian

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) microparticles are used in various disorders for the controlled or sustained release of drugs, with the management of salivary gland pathologies possible using this technology. There is no record of the response to such microparticles in the glandular parenchyma. The purpose of this study was to assess the morphological changes in the parotid gland when injected with a single dose of PLGA microparticles. We used 12 adult female Sprague Dawley rats (Rattus norvegicus) that were injected into their right parotid gland with sterile vehicle solution (G1, n=4), 0.5 mg PLGA microparticles (G2, n=4), and 0.75 mg PLGA microparticles (G3, n=4); the microparticles were dissolved in a sterile vehicle solution. The intercalar and striated ducts lumen, the thickness of the acini and the histology aspect in terms of the parenchyma organization, cell morphology of acini and duct system, the presence of polymeric residues, and inflammatory response were determined at 14 days post-injection. The administration of the compound in a single dose modified some of the morphometric parameters of parenchyma (intercalar duct lumen and thickness of the glandular acini) but did not induce tissue inflammatory response, despite the visible presence of polymer waste. This suggests that PLGA microparticles are biocompatible with the parotid tissue, making it possible to use intraglandular controlled drug administration. PMID:24228103

  11. Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite scaffolds for bone tissue engineering.

    PubMed

    Qian, Junmin; Xu, Weijun; Yong, Xueqing; Jin, Xinxia; Zhang, Wei

    2014-03-01

    In this study, biomorphic poly(dl-lactic-co-glycolic acid)/nano-hydroxyapatite (PLGA/nHA) composite scaffolds were successfully prepared using cane as a template. The porous morphology, phase, compression characteristics and in vitro biocompatibility of the PLGA/nHA composite scaffolds and biomorphic PLGA scaffolds as control were investigated. The results showed that the biomorphic scaffolds preserved the original honeycomb-like architecture of cane and exhibited a bimodal porous structure. The average channel diameter and micropore size of the PLGA/nHA composite scaffolds were 164 ± 52 μm and 13 ± 8 μm, respectively, with a porosity of 89.3 ± 1.4%. The incorporation of nHA into PLGA decreased the degree of crystallinity of PLGA, and significantly improved the compressive modulus of biomorphic scaffolds. The in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated that the biomorphic PLGA/nHA composite scaffolds could better support cell attachment, proliferation and differentiation than the biomorphic PLGA scaffolds. The localization depth of MC3T3-E1 cells within the channels of the biomorphic PLGA/nHA composite scaffolds could reach approximately 400 μm. The results suggested that the biomorphic PLGA/nHA composite scaffolds were promising candidates for bone tissue engineering.

  12. In vitro biocompatibility of polypyrrole/PLGA conductive nanofiber scaffold with cultured rat hepatocytes

    NASA Astrophysics Data System (ADS)

    Chu, Xue-Hui; Xu, Qian; Feng, Zhang-Qi; Xiao, Jiang-Qiang; Li, Qiang; Sun, Xi-Tai; Cao, Yang; Ding, Yi-Tao

    2014-09-01

    To intruduce conductive biomaterial into liver tissue engineering, a conductive nanofiber scaffold, polypyrrole/poly(lactic-co-glycolic)acid(PLGA), was designed and prepared via electro-spinning and oxidative polymerization. Effects of the scaffold on hepatocyte adhesion, viability and function were then investigated. SEM revealed pseudopodium formation and abundant extracellular matrix on the surface of PLGA membrane and polypyrrole/PLGA membrane. The adhesion rate, cellular activity, urea synthesis and albumin secretion of the hepatocytes cultured on polypyrrole/PLGA group were similar to those on the PLGA group, but were significantly higher than those on the control group. There were no significant differences in concentrations of LDH and TNF-α among three groups. These results suggested the potential application of this conductive nanofiber scaffold as a suitable substratum for hepatocyte culturing in liver tissue engineering.

  13. Poly(amino acid) functionalized maghemite and gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Perego, Davide; Masciocchi, Norberto; Guagliardi, Antonietta; Domínguez-Vera, José Manuel; Gálvez, Natividad

    2013-02-01

    Bimodal MRI/OI imaging probes are of great interest in nanomedicine. Although many organic polymers have been studied thoroughly for in vivo applications, reports on the use of poly(amino acid)s as coating polymers are scarce. In this paper, poly-(d-glutamic acid, d-lysine) (PGL) has been used for coating maghemite and gold nanoparticles. An advantage of this flexible and biocompatible polymer is that, once anchored to the nanoparticle surface, dangling lysine amino groups are available for the incorporation of new functionalities. As an example, Alexa Fluor derivatives have been attached to PGL-coated maghemite nanoparticles to obtain magnetic/fluorescent materials. These dual-property materials could be used as bimodal MRI/OI probes for in vivo imaging.

  14. Synthesis of copper sulphide nanoparticles in carboxylic acids as solvent.

    PubMed

    Armelao, Lidia; Camozzo, Daniele; Gross, Silvia; Tondello, Eugenio

    2006-02-01

    A novel method for the preparation of CuS nanoparticles based on the fast nucleation of the sulphide has been developed. The particles have been synthesized by reaction of thioacetic acid with water and copper carboxylates (acetate, propionate) in the corresponding carboxylic acid (acetic, propionic) as a solvent. The use of carboxylic acids presents several advantages: (i) the hydrolysis of the C-S bond is favoured thus producing a fast CuS supersaturation and a high nucleation rate; (ii) the mobility of the precursor molecules is limited so that nucleation events are favoured with respect to particle growth; (iii) the low dielectric constant of the medium stabilises the nanoparticles dispersion by reducing the critical coagulation concentration. The prepared nanoparticles were investigated by UV-Vis spectroscopy, X-ray photoelectron spectroscopy, atomic force microscopy and dynamic light scattering. The nanoparticle suspensions are clear and characterized by a blue-shifted adsorption edge with respect to bulk CuS. Light scattering measurements performed on acetic acid suspensions evidence the formation of monodispersed nanoparticles with an average diameter of about 5 nm.

  15. Fabrication of pillared PLGA microvessel scaffold using femtosecond laser ablation

    PubMed Central

    Wang, Hsiao-Wei; Cheng, Chung-Wei; Li, Ching-Wen; Chang, Han-Wei; Wu, Ping-Han; Wang, Gou-Jen

    2012-01-01

    One of the persistent challenges confronting tissue engineering is the lack of intrinsic microvessels for the transportation of nutrients and metabolites. An artificial microvascular system could be a feasible solution to this problem. In this study, the femtosecond laser ablation technique was implemented for the fabrication of pillared microvessel scaffolds of polylactic-co-glycolic acid (PLGA). This novel scaffold facilitates implementation of the conventional cell seeding process. The progress of cell growth can be observed in vitro by optical microscopy. The problems of becoming milky or completely opaque with the conventional PLGA scaffold after cell seeding can be resolved. In this study, PLGA microvessel scaffolds consisting of 47 μm × 80 μm pillared branches were produced. Results of cell culturing of bovine endothelial cells demonstrate that the cells adhere well and grow to surround each branch of the proposed pillared microvessel networks. PMID:22605935

  16. Paclitaxel-loaded star-shaped copolymer nanoparticles for enhanced malignant melanoma chemotherapy against multidrug resistance.

    PubMed

    Su, Yongsheng; Hu, Jian; Huang, Zhibin; Huang, Yubin; Peng, Bingsheng; Xie, Ni; Liu, Hui

    2017-01-01

    Malignant melanoma (MM) is the most dangerous type of skin cancer with annually increasing incidence and death rates. However, chemotherapy for MM is restricted by low topical drug concentration and multidrug resistance. In order to surmount the limitation and to enhance the therapeutic effect on MM, a new nanoformulation of paclitaxel (PTX)-loaded cholic acid (CA)-functionalized star-shaped poly(lactide-co-glycolide) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (NPs) (shortly PTX-loaded CA-PLGA-TPGS NPs) was fabricated by a modified method of nanoprecipitation. The particle size, zeta potential, morphology, drug release profile, drug encapsulation efficiency, and loading content of PTX-loaded NPs were detected. As shown by confocal laser scanning, NPs loaded with coumarin-6 were internalized by human melanoma cell line A875. The cellular uptake efficiency of CA-PLGA-TPGS NPs was higher than those of PLGA NPs and PLGA-TPGS NPs. The antitumor effects of PTX-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that star-shaped PTX-loaded CA-PLGA-TPGS NPs were significantly superior to commercial PTX formulation Taxol(®). Such drug delivery nanocarriers are potentially applicable to the improvement of clinical MM therapy.

  17. Paclitaxel-loaded star-shaped copolymer nanoparticles for enhanced malignant melanoma chemotherapy against multidrug resistance

    PubMed Central

    Su, Yongsheng; Hu, Jian; Huang, Zhibin; Huang, Yubin; Peng, Bingsheng; Xie, Ni; Liu, Hui

    2017-01-01

    Malignant melanoma (MM) is the most dangerous type of skin cancer with annually increasing incidence and death rates. However, chemotherapy for MM is restricted by low topical drug concentration and multidrug resistance. In order to surmount the limitation and to enhance the therapeutic effect on MM, a new nanoformulation of paclitaxel (PTX)-loaded cholic acid (CA)-functionalized star-shaped poly(lactide-co-glycolide) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (NPs) (shortly PTX-loaded CA-PLGA-TPGS NPs) was fabricated by a modified method of nanoprecipitation. The particle size, zeta potential, morphology, drug release profile, drug encapsulation efficiency, and loading content of PTX-loaded NPs were detected. As shown by confocal laser scanning, NPs loaded with coumarin-6 were internalized by human melanoma cell line A875. The cellular uptake efficiency of CA-PLGA-TPGS NPs was higher than those of PLGA NPs and PLGA-TPGS NPs. The antitumor effects of PTX-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that star-shaped PTX-loaded CA-PLGA-TPGS NPs were significantly superior to commercial PTX formulation Taxol®. Such drug delivery nanocarriers are potentially applicable to the improvement of clinical MM therapy. PMID:28293102

  18. BIODEGRADABLE NANOPARTICLES MIMICKING PLATELET BINDING AS A TARGETED AND CONTROLLED DRUG DELIVERY SYSTEM

    PubMed Central

    Kona, Soujanya; Dong, Jing-Fei; Liu, Yaling; Tan, Jifu

    2012-01-01

    This research aims to develop targeted nanoparticles as drug carriers to the injured arterial wall under fluid shear stress by mimicking the natural binding ability of platelets via interactions of glycoprotein Ib-alpha (GP Ibα) of platelets with P-selectin of damaged endothelial cells (ECs) and/or with von Willebrand factor (vWF) of the subendothelium. Drug-loaded poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles were formulated using a standard emulsion method and conjugated with glycocalicin, the external fraction of platelet GPIbα, via carbodiimide chemistry. Surface-coated and cellular uptake studies in ECs showed that conjugation of PLGA nanoparticles with GPIb significantly increased nanoparticle adhesion to P-selectin- and vWF-coated surfaces as well as nanoparticle uptake by activated ECs under fluid shear stresses. In addition, effects of nanoparticle size and shear stress on adhesion efficiency were characterized through parallel flow chamber studies. The observed decrease in bound nanoparticle density with increased particle sizes and shear stresses is also explained through a computational model. Our results demonstrate that the GPIb-conjugated PLGA nanoparticles can be used as a targeted and controlled drug delivery system under flow conditions at the site of vascular injury. PMID:22172292

  19. Elucidation of the physicomechanical and ab initio quantum energy transitions of a crosslinked PLGA scaffold.

    PubMed

    Sibambo, Sibongile R; Pillay, Viness; Choonara, Yahya E; Khan, Riaz A; Sweet, Joe L

    2007-09-01

    This study elucidated the in vitro physicomechanical transitions of a crosslinked polylactic-co-glycolic acid (PLGA) scaffold, utilizing quantum mechanics to compute the ab initio energy requirements of a salted-out and subsequently crosslinked PLGA scaffold interacting with simulated physiological fluid, phosphate buffered saline (PBS) (pH 7.4, 37 degrees C) at a molecular level. Twenty-six salted-out PLGA scaffolds were formulated using a four factor, two centerpoint quadratic Face-Centered Central Composite Design (FCCD). PLGA molecular mass, PLGA concentration, water volume and salting-out reaction time were the dependant formulation variables. Subsequent to PLGA solubilization in dimethyl formamide (DMF), protonated water was added to induce salting-out of PLGA into a scaffolds that were immersed in PBS, oscillated at 100 rpm, and analyzed at pre-determined time intervals for their physicomechanical and ab initio quantum energy transitions. Results indicated that the matrix resilience (MR) decreased with longer incubation periods (MR=35-45%) at day 30. Scaffolds salted-out using higher PLGA concentrations exhibited minimal changes in MR and the matrix ability to absorb energy was found to closely correlate with the scaffold residence time in PBS. Spartan-based ab initio quantum energy predictions elucidated the potential scaffold stability from a molecular viewpoint and its suitability for use in rate-modulated drug delivery.

  20. PLGA nanometer surface features manipulate fibronectin interactions for improved vascular cell adhesion.

    PubMed

    Miller, Derick C; Haberstroh, Karen M; Webster, Thomas J

    2007-06-01

    The largest cause of mortality in the Western world is atherosclerotic vascular disease. Many of these diseases require synthetic vascular grafts; however, their patency rate is only 30% in small (<6 mm) diameter vascular grafts after 5 years of implantation. In an effort to increase small diameter vascular graft success, researchers have been designing random nanostructured surface features which enhance vascular cell functions. However, for the present study, highly-controllable, nanostructured features on poly(lactic-co-glycolic acid) (PLGA) surfaces were formulated. To create ordered nanostructured roughness on PLGA surfaces, either 500, 200, or 100 nm polystyrene nanospheres were separately placed onto mica. These were then used as a template for creating an inverse poly(dimethylsiloxane) mold which was utilized to cast PLGA. Compared to all other PLGA films formulated, AFM results demonstrated greater initial fibronectin spreading on PLGA which possessed spherical 200 nm features. Compared to smooth PLGA, PLGA with 500 or 100 nm surface features, results further showed that PLGA with 200 nm spherical features promoted vascular cell (specifically, endothelial, and smooth muscle cell) adhesion. In this manner, the present study demonstrated a specific nanometer surface feature size that promoted fibronectin spreading and subsequent vascular cell adhesion; criteria critical to vascular graft success.

  1. α-Mangostin-encapsulated PLGA nanoparticles inhibit pancreatic carcinogenesis by targeting cancer stem cells in human, and transgenic (KrasG12D, and KrasG12D/tp53R270H) mice

    PubMed Central

    Verma, Raj Kumar; Yu, Wei; Shrivastava, Anju; Shankar, Sharmila; Srivastava, Rakesh K.

    2016-01-01

    Activation of sonic hedgehog (Shh) in cancer stem cell (CSC) has been demonstrated with aggressiveness of pancreatic cancer. In order to enhance the biological activity of α-mangostin, we formulated mangostin-encapsulated PLGA nanoparticles (Mang-NPs) and examined the molecular mechanisms by which they inhibit human and KC mice (PdxCre;LSL-KrasG12D) pancreatic CSC characteristics in vitro, and pancreatic carcinogenesis in KPC (PdxCre;LSLKrasG12D;LSL-Trp53R172H) mice. Mang-NPs inhibited human and KrasG12D mice pancreatic CSC characteristics in vitro. Mang-NPs also inhibited EMT by up-regulating E-cadherin and inhibiting N-cadherin and transcription factors Slug, and pluripotency maintaining factors Nanog, c-Myc, and Oct4. Furthermore, Mang-NPs inhibited the components of Shh pathway and Gli targets. In vivo, Mang-NPs inhibited the progression of pancreatic intraneoplasia to pancreatic ductal adenocarcinoma and liver metastasis in KPC mice. The inhibitory effects of Mang-NPs on carcinogenesis in KPC mice were associated with downregulation of pluripotency maintaining factors (c-Myc, Nanog and Oct4), stem cell markers (CD24 and CD133), components of Shh pathway (Gli1, Gli2, Patched1/2, and Smoothened), Gli targets (Bcl-2, XIAP and Cyclin D1), and EMT markers and transcription factors (N-cadherin, Slug, Snail and Zeb1), and upregulation of E-cadherin. Overall, our data suggest that Mang-NPs can inhibit pancreatic cancer growth, development and metastasis by targeting Shh pathway. PMID:27624879

  2. Induction of a balanced Th1/Th2 immune responses by co-delivery of PLGA/ovalbumin nanospheres and CpG ODNs/PEI-SWCNT nanoparticles as TLR9 agonist in BALB/c mice.

    PubMed

    Ebrahimian, Mahboubeh; Hashemi, Maryam; Maleki, Mohsen; Abnous, Khalil; Hashemitabar, Gholamreza; Ramezani, Mohammad; Haghparast, Alireza

    2016-10-29

    To develop effective and safe vaccines with reduced dose of antigen and adjuvant, intelligent delivery systems are required. Many delivery systems have been developed to enhance the biological activity of cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODN) as both immunotherapeutic agents and vaccine adjuvants. In this study we designed a novel CpG ODN delivery system based on single-walled carbon nanotube (SWCNT) functionalized with polyethylenimine (PEI) and alkylcarboxylated PEI (AL-PEI). The physicochemical characteristics, cytotoxicity and cellular uptake studies of these carriers were performed. All carriers were conjugated with CpG ODN followed by co-delivery with ovalbumin (OVA) encapsulated into poly (lactic-co-glycolic acid) nanospheres (PLGA NSs) to enhance the induction of immune responses. The effect of these formulations on antibody (IgG1, IgG2a) and cytokine (IL-1β, IFN-γ, IL-4) production was evaluated in an in vivo experiment. The results showed that all nano-adjuvant formulations had a strong influence in up-regulation of IFN-γ and IL-4 in parallel with high IgG1-IgG2a isotype antibody titers in mice. In particular, SWCNT-AL-PEI nano-adjuvant formulation generated a balanced Th1 and Th2 immune response with more biased toward Th1 response without exhibiting any inflammatory and toxic effects. Therefore this nano-adjuvant formulation could be used as an efficient prophylactic immune responses agent.

  3. Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy

    PubMed Central

    Chu, Qiuchen; Xu, Hong; Gao, Meng; Guan, Xin; Liu, Hongyan; Deng, Sa; Huo, Xiaokui; Liu, Kexin; Tian, Yan; Ma, Xiaochi

    2016-01-01

    Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5-fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and

  4. Development of Risperidone PLGA Microspheres

    PubMed Central

    D'Souza, Susan; Faraj, Jabar A.; Giovagnoli, Stefano; DeLuca, Patrick P.

    2014-01-01

    The aim of this study was to design and evaluate biodegradable PLGA microspheres for sustained delivery of Risperidone, with an eventual goal of avoiding combination therapy for the treatment of schizophrenia. Two PLGA copolymers (50 : 50 and 75 : 25) were used to prepare four microsphere formulations of Risperidone. The microspheres were characterized by several in vitro techniques. In vivo studies in male Sprague-Dawley rats at 20 and 40 mg/kg doses revealed that all formulations exhibited an initial burst followed by sustained release of the active moiety. Additionally, formulations prepared with 50 : 50 PLGA had a shorter duration of action and lower cumulative AUC levels than the 75 : 25 PLGA microspheres. A simulation of multiple dosing at weekly or 15-day regimen revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Overall, the clinical use of Formulations A, B, C, or D will eliminate the need for combination oral therapy and reduce time to achieve steady state, with a smaller washout period upon cessation of therapy. Results of this study prove the suitability of using PLGA copolymers of varying composition and molecular weight to develop sustained release formulations that can tailor in vivo behavior and enhance pharmacological effectiveness of the drug. PMID:24616812

  5. Sensitive determination of nucleic acids using organic nanoparticle fluorescence probes

    NASA Astrophysics Data System (ADS)

    Zhou, Yunyou; Bian, Guirong; Wang, Leyu; Dong, Ling; Wang, Lun; Kan, Jian

    2005-06-01

    This paper describes the preparation of organic nanoparticles by reprecipitation method under sonication and vigorous stirring. Transmission electron microscopy (TEM) was used to characterize the size and size distribution of the luminescent nanoparticles. Their average diameter was about 25 nm with a size variation of ±18%. The fluorescence decay lifetime of the nanoparticles also was determined on a self-equipped fluorospectrometer with laser light source. The lifetime (˜0.09 μs) of nanoparticles is about three times long as that of the monomer. The nanoparticles were in abundant of hydrophilic groups, which increased their miscibility in aqueous solution. These organic nanoparticles have high photochemical stability, excellent resistance to chemical degradation and photodegradation, and a good fluorescence quantum yield (25%). The fluorescence can be efficiently quenched by nucleic acids. Based on the fluorescence quenching of nanoparticles, a fluorescence quenching method was developed for determination of microamounts of nucleic acids by using the nanoparticles as a new fluorescent probe. Under optimal conditions, maximum fluorescence quenching is produced, with maximum excitation and emission wavelengths of 345 and 402 nm, respectively. Under optimal conditions, the calibration graphs are linear over the range 0.4-19.0 μg ml -1 for calf thymus DNA (ct-DNA) and 0.3-19.0 μg ml -1 for fish sperm DNA (fs-DNA). The corresponding detection limits are 0.25 μg ml -1 for ct-DNA and 0.17 μg ml -1 for fs-DNA. The relative standard deviation of six replicate measurements is 1.3-2.1%. The method is simple, rapid and sensitive with wide linear range. The recovery and relative standard deviation are very satisfactory.

  6. Investigation on the ion pair amphiphiles and their in vitro release of amantadine drug based on PLGA-PEG-PLGA gel

    NASA Astrophysics Data System (ADS)

    Yang, Xiaoxia; Ji, Xiaoqing; Shi, Chunhuan; Liu, Jing; Wang, Haiyang; Luan, Yuxia

    2014-12-01

    The amantadine drug and oleic acid surfactant are used to form amantadine-based ion pair amphiphiles based on proton transfer reaction between the drug and the surfactant molecules. The ion pair amphiphiles are characterized by 1H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, and X-ray diffraction. Self-assembly properties of amantadine-based ion pair amphiphiles are studied by surface tension determination, transmission electron microscopy, zeta potential, and dynamic light scattering. The aggregation behavior studies indicate that the as-prepared ion pair amphiphiles can self-assemble into vesicles with the size of 200-300 nm in aqueous solution. The drug release results show that the amantadine release rate could be well controlled by incorporating the amantadine-based ion pair vesicles in poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) copolymer hydrogel. The drug release from the AT-OA vesicle-loaded PLGA-PEG-PLGA hydrogel is significantly inhibited in comparison with the AT-loaded PLGA-PEG-PLGA hydrogel. The present work thus demonstrates that the vesicle-loaded hydrogel is a good candidate for the drug delivery system with long-term controlled drug release behavior.

  7. Non-viral nucleic acid containing nanoparticles as cancer therapeutics

    PubMed Central

    Kozielski, Kristen L.; Rui, Yuan

    2016-01-01

    Introduction The delivery of nucleic acids such as DNA and short interfering RNA (siRNA) is promising for the treatment of many diseases, including cancer, by enabling novel biological mechanisms of action. Non-viral nanoparticles are a promising class of nucleic acid carriers that can be designed to be safer and more versatile than traditional viral vectors. Areas covered In this review, recent advances in the intracellular delivery of DNA and siRNA are described with a focus on non-viral nanoparticle-based delivery methods. Material properties that have enabled successful delivery are discussed as well as applications that have directly been applied to cancer therapy. Strategies to co-deliver different nucleic acids are highlighted, as are novel targets for nucleic acid co-delivery. Expert opinion The treatment of complex genetically-based diseases such as cancer can be enabled by safe and effective intracellular delivery of multiple nucleic acids. Non-viral nanoparticles can be fabricated to deliver multiple nucleic acids to the same cell simultaneously to prevent tumor cells from easily compensating for the knockdown or overexpression of one genetic target. The continued innovation of new therapeutic modalities and non-viral nanotechnologies to provide target-specific and personalized forms of gene therapy hold promise for genetic medicine to treat diseases like cancer in the clinic. PMID:27248202

  8. Nanoparticle formulation of ormeloxifene for pancreatic cancer

    PubMed Central

    Khan, Sheema; Chauhan, Neeraj; Yallapu, Murali M.; Ebeling, Mara C.; Balakrishna, Swathi; Ellis, Robert T.; Thompson, Paul A.; Balabathula, Pavan; Behrman, Stephen W.; Zafar, Nadeem; Singh, Man Mohan; Halaweish, Fathi T.; Jaggi, Meena; Chauhan, Subhash C.

    2015-01-01

    Pancreatic cancer is the fourth most prevalent cancer with about an 85% mortality rate; thus, an utmost need exists to discover new therapeutic modalities that would enhance therapy outcomes of this disease with minimal or no side effects. Ormeloxifene (ORM), a synthetic molecule, has exhibited potent anti-cancer effects through inhibition of important oncogenic and proliferation signaling pathways. However, the anti-cancer efficacy of ORM can be further improved by developing its nanoformulation, which will also offer tumor specific targeted delivery. Therefore, we have developed a novel ORM encapsulated poly(lactic-co-glycolic acid) nanoparticle (NP) formulation (PLGA-ORM NP). This formulation was characterized for particle size, chemical composition, and drug loading efficiency, using various physico-chemical methods (TEM, FT-IR, DSC, TGA, and HPLC). Because of its facile composition, this novel formulation is compatible with antibody/aptamer conjugation to achieve tumor specific targeting. The particle size analysis of this PLGA-ORM formulation (~ 100 nm) indicates that this formulation can preferentially reach and accumulate in tumors by the Enhanced Permeability and Retention (EPR) effect. Cellular uptake and internalization studies demonstrate that PLGA-ORM NPs escape lysosomal degradation, providing efficient endosomal release to cytosol. PLGA-ORM NPs showed remarkable anti-cancer potential in various pancreatic cancer cells (HPAF-II, BxPC-3, Panc-1, MiaPaca) and a BxPC-3 xenograft mice model resulting in increased animal survival. PLGA-ORM NPs suppressed pancreatic tumor growth via suppression of Akt phosphorylation and expression of MUC1, HER2, PCNA, CK19 and CD31. This study suggests that the PLGA-ORM formulation is highly efficient for the inhibition of pancreatic tumor growth and thus can be valuable for the treatment of pancreatic cancer in the future. PMID:25890768

  9. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects

    PubMed Central

    Lin, Kai-Feng; Fan, Jun-Jun; Hu, Gang; Dong, Xin; Zhao, Yi-Nan; Song, Yue; Guo, Zhong-Shang

    2016-01-01

    A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration. PMID:27652269

  10. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects.

    PubMed

    He, Shu; Lin, Kai-Feng; Fan, Jun-Jun; Hu, Gang; Dong, Xin; Zhao, Yi-Nan; Song, Yue; Guo, Zhong-Shang; Bi, Long; Liu, Jian

    2016-01-01

    A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration.

  11. Electrophoretic deposition and characterization of nanocomposites and nanoparticles on magnesium substrates

    NASA Astrophysics Data System (ADS)

    Tian, Qiaomu; Liu, Huinan

    2015-05-01

    This study introduces a triphasic design of biodegradable materials composed of nanophase hydroxyapatite (nHA), poly(lactic-co-glycolic acid) (PLGA), and magnesium (Mg) substrates for musculoskeletal implant applications. Specifically, nHA_PLGA composites and nHA nanoparticles were synthesized, deposited on three-dimensional Mg substrates using electrophoretic deposition (EPD), and characterized. The three components involved, that is, nHA, PLGA, and Mg are all biodegradable in the human body, thus promising for biodegradable implant and device applications. Mg and its alloys are attractive for musculoskeletal implant applications due to their comparable modulus and strength to cortical bone. Controlling the interface of Mg with the biological environment, however, is the key challenge that currently limits this biodegradable metal for broad applications in medical implants. This article particularly focuses on creating nanostructured interface between the biodegradable Mg and surrounding tissue for the dual purposes of (1) mediating the degradation of the Mg-based substrates and (2) potentially enhancing osteointegration. Nanophase hydroxyapatite (nHA) is an excellent candidate as a coating material due to its osteoconductivity, while the polymer phase promotes interfacial adhesion between the nHA and Mg. Moreover, the degradation products of PLGA and Mg neutralize each other. Surface characterization showed successful deposition of nHA_PLGA composite microspheres and nHA nanoparticles on Mg substrates using EPD. Mg substrates coated with nHA_PLGA composites showed greater adhesion strength when compared with nHA coating, and slower corrosion rate than nHA coated Mg and non-coated Mg. The triphasic composites of nHA, PLGA and Mg are promising as the next-generation biodegradable materials for medical applications.

  12. Electrophoretic deposition and characterization of nanocomposites and nanoparticles on magnesium substrates.

    PubMed

    Tian, Qiaomu; Liu, Huinan

    2015-05-01

    This study introduces a triphasic design of biodegradable materials composed of nanophase hydroxyapatite (nHA), poly(lactic-co-glycolic acid) (PLGA), and magnesium (Mg) substrates for musculoskeletal implant applications. Specifically, nHA_PLGA composites and nHA nanoparticles were synthesized, deposited on three-dimensional Mg substrates using electrophoretic deposition (EPD), and characterized. The three components involved, that is, nHA, PLGA, and Mg are all biodegradable in the human body, thus promising for biodegradable implant and device applications. Mg and its alloys are attractive for musculoskeletal implant applications due to their comparable modulus and strength to cortical bone. Controlling the interface of Mg with the biological environment, however, is the key challenge that currently limits this biodegradable metal for broad applications in medical implants. This article particularly focuses on creating nanostructured interface between the biodegradable Mg and surrounding tissue for the dual purposes of (1) mediating the degradation of the Mg-based substrates and (2) potentially enhancing osteointegration. Nanophase hydroxyapatite (nHA) is an excellent candidate as a coating material due to its osteoconductivity, while the polymer phase promotes interfacial adhesion between the nHA and Mg. Moreover, the degradation products of PLGA and Mg neutralize each other. Surface characterization showed successful deposition of nHA_PLGA composite microspheres and nHA nanoparticles on Mg substrates using EPD. Mg substrates coated with nHA_PLGA composites showed greater adhesion strength when compared with nHA coating, and slower corrosion rate than nHA coated Mg and non-coated Mg. The triphasic composites of nHA, PLGA and Mg are promising as the next-generation biodegradable materials for medical applications.

  13. Tracking the in vivo release of bioactive NRG from PLGA and PEG-PLGA microparticles in infarcted hearts.

    PubMed

    Pascual-Gil, S; Simón-Yarza, T; Garbayo, E; Prosper, F; Blanco-Prieto, M J

    2015-12-28

    The growth factor neuregulin (NRG) is one of the most promising candidates in protein therapy as potential treatment for myocardial infarction (MI). In the last few years, biomaterial based delivery systems, such as polymeric microparticles (MPs) made of poly(lactic co glycolic acid) and polyethylene glycol (PLGA and PEG-PLGA MPs), have improved the efficacy of protein therapy in preclinical studies. However, no cardiac treatment based on MPs has yet been commercialized since this is a relatively new field and total characterization of polymeric MPs remains mandatory before they reach the clinical arena. Therefore, the objective of this study was to characterize the in vivo release, bioactivity and biodegradation of PLGA and PEG-PLGA MPs loaded with biotinylated NRG in a rat model of MI. The effect of PEGylation in the clearance of the particles from the cardiac tissue was also evaluated. Interestingly, MPs were detected in the cardiac tissue for up to 12 weeks after administration. In vivo release analysis showed that bNRG was released in a controlled manner throughout the twelve week study. Moreover, the biological cardiomyocyte receptor (ErbB4) for NRG was detected in its activated form only in those animals treated with bNRG loaded MPs. On the other hand, the PEGylation strategy was effective in diminishing phagocytosis of these MPs compared to noncoated MPs in the long term (12 weeks after injection). Taking all this together, we report new evidence in favor of the use of polymeric PLGA and PEG-PLGA MPs as delivery systems for treating MI, which could be soon included in clinical trials.

  14. PLGA nanofiber membranes loaded with epigallocatechin-3-O-gallate are beneficial to prevention of postsurgical adhesions

    PubMed Central

    Shin, Yong Cheol; Yang, Won Jun; Lee, Jong Ho; Oh, Jin-Woo; Kim, Tai Wan; Park, Jong-Chul; Hyon, Suong-Hyu; Han, Dong-Wook

    2014-01-01

    This study concentrates on the development of biodegradable nanofiber membranes with controlled drug release to ensure reduced tissue adhesion and accelerated healing. Nanofibers of poly(lactic-co-glycolic acid) (PLGA) loaded with epigallocatechin-3-O-gallate (EGCG), the most bioactive polyphenolic compound in green tea, were electrospun. The physicochemical and biomechanical properties of EGCG-releasing PLGA (E-PLGA) nanofiber membranes were characterized by atomic force microscopy, EGCG release and degradation profiles, and tensile testing. In vitro antioxidant activity and hemocompatibility were evaluated by measuring scavenged reactive oxygen species levels and activated partial thromboplastin time, respectively. In vivo antiadhesion efficacy was examined on the rat peritonea with a surgical incision. The average fiber diameter of E-PLGA membranes was approximately 300–500 nm, which was almost similar to that of pure PLGA equivalents. E-PLGA membranes showed sustained EGCG release mediated by controlled diffusion and PLGA degradation over 28 days. EGCG did not adversely affect the tensile strength of PLGA membranes, whereas it significantly decreased the elastic modulus and increased the strain at break. E-PLGA membranes were significantly effective in both scavenging reactive oxygen species and extending activated partial thromboplastin time. Macroscopic observation after 1 week of surgical treatment revealed that the antiadhesion efficacy of E-PLGA nanofiber membranes was significantly superior to those of untreated controls and pure PLGA equivalents, which was comparable to that of a commercial tissue-adhesion barrier. In conclusion, the E-PLGA hybrid nanofiber can be exploited to craft strategies for the prevention of postsurgical adhesions. PMID:25187710

  15. PLGA nanofiber membranes loaded with epigallocatechin-3-O-gallate are beneficial to prevention of postsurgical adhesions.

    PubMed

    Shin, Yong Cheol; Yang, Won Jun; Lee, Jong Ho; Oh, Jin-Woo; Kim, Tai Wan; Park, Jong-Chul; Hyon, Suong-Hyu; Han, Dong-Wook

    2014-01-01

    This study concentrates on the development of biodegradable nanofiber membranes with controlled drug release to ensure reduced tissue adhesion and accelerated healing. Nanofibers of poly(lactic-co-glycolic acid) (PLGA) loaded with epigallocatechin-3-O-gallate (EGCG), the most bioactive polyphenolic compound in green tea, were electrospun. The physicochemical and biomechanical properties of EGCG-releasing PLGA (E-PLGA) nanofiber membranes were characterized by atomic force microscopy, EGCG release and degradation profiles, and tensile testing. In vitro antioxidant activity and hemocompatibility were evaluated by measuring scavenged reactive oxygen species levels and activated partial thromboplastin time, respectively. In vivo antiadhesion efficacy was examined on the rat peritonea with a surgical incision. The average fiber diameter of E-PLGA membranes was approximately 300-500 nm, which was almost similar to that of pure PLGA equivalents. E-PLGA membranes showed sustained EGCG release mediated by controlled diffusion and PLGA degradation over 28 days. EGCG did not adversely affect the tensile strength of PLGA membranes, whereas it significantly decreased the elastic modulus and increased the strain at break. E-PLGA membranes were significantly effective in both scavenging reactive oxygen species and extending activated partial thromboplastin time. Macroscopic observation after 1 week of surgical treatment revealed that the antiadhesion efficacy of E-PLGA nanofiber membranes was significantly superior to those of untreated controls and pure PLGA equivalents, which was comparable to that of a commercial tissue-adhesion barrier. In conclusion, the E-PLGA hybrid nanofiber can be exploited to craft strategies for the prevention of postsurgical adhesions.

  16. Improving Protein Stability and Controlling Protein Release by Adding Poly (Cyclohexane-1, 4-Diyl Acetone Dimethylene Ketal) to PLGA Microspheres.

    PubMed

    Wang, Chenhui; Yu, Changhui; Yu, Kongtong; Teng, Lesheng; Liu, Jiaxin; Wang, Xuesong; Sun, Fengying; Li, Youxin

    2015-01-01

    The use of biodegradable polymers such as PLGA to encapsulate therapeutic proteins for their controlled release has received tremendous interest. However, an acidic environment caused by PLGA degradation productions leads to protein incomplete release and chemical degradation. The aim of this study was to develop novel PCADK/PLGA microspheres to improve protein stability and release behavior. Bovine serum albumin (BSA) incubated in PCADK and PLGA degradation products was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size exclusion chromatography (SEC-HPLC), circular dichroism (CD) and fluorescence spectroscopy. Blended microspheres of PCADK/PLGA were prepared in different ratios and the release behaviors of the microspheres and the protein stability were then measured. The degradation properties of the microspheres and the pH inside the microspheres were systematically investigated by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) to examine the mechanism of autocatalytic degradation and protein stability. BSA was more stable in the presence of PCADK monomers than it was in the presence of PLGA monomers, revealing that PCADK is highly compatible with this protein. PCADK/PLGA microspheres were successfully prepared, and 2/8 was determined to be the optimal ratio. Further, 43% of the BSA formed water-insoluble aggregates in the presence of PCADK/PLGA microspheres, compared with 57% for the PLGA microspheres, demonstrating that the BSA encapsulated in PCADK/PLGA blended microspheres was more stable than in PLGA microspheres. The PCADK/PLGA blended microspheres improved protein stability and release behavior, providing a promising protein drug delivery system.

  17. On-resin synthesis of an acylated and fluorescence-labeled cyclic integrin ligand for modification of poly(lactic-co-glycolic acid).

    PubMed

    Hassert, Rayk; Hoffmeister, Peter-Georg; Pagel, Mareen; Hacker, Michael; Schulz-Siegmund, Michaela; Beck-Sickinger, Annette G

    2012-11-01

    Cyclic Arg-Gly-Asp (RGD) peptides show remarkable affinity and specificity to integrin receptors and mediate important physiological effects in tumor angiogenesis. Additionally, they are one of the keyplayers in improving the biocompatibility of biomaterials. The fully biodegradable polymer poly(lactic-co-glycolic acid) (PLGA) is frequently used for biomedical implants and can be applied as nanoparticles for drug delivery. The aim of this work was the generation of a lipidated c[RGDfK] peptide including a second functionality for coating of hydrophobic PLGA. Therefore, we established a general and straightforward strategy for the introduction of two different modifications into the same c[RGDfK] peptide. This allowed the generation of a palmitoylated integrin-binding lipopeptide that shows high affinity to PLGA. Additionally, we coupled 5(6)-carboxyfluorescein to the second site for modification to enable sensitive quantification of the immobilized lipopeptide on PLGA. In conclusion, we present a synthesis protocol that enables the preparation of c[RGDfK] lipopeptides with a strong affinity to PLGA and an additional site for modifications. This will provide the opportunity to introduce a variety of effector molecules site-specifically to the c[RGDfK] lipopeptide, which will enable the introduction of multifunctionality into c[RGDfK]-coated PLGA devices or nanoparticles.

  18. Biopharmaceutical profile of hydrogels containing pranoprofen-loaded PLGA nanoparticles for skin administration: In vitro, ex vivo and in vivo characterization.

    PubMed

    Abrego, Guadalupe; Alvarado, Helen; Souto, Eliana B; Guevara, Bessy; Bellowa, Lyda Halbaut; Garduño, Maria Luisa; Garcia, María Luisa; Calpena, Ana C

    2016-03-30

    Pranoprofen (PF)-loaded nanoparticles (PF-F1NPs and PF-F2NPs) have been formulated into blank hydrogels (HG_PF-F1NPs and HG_PF-F1NPs) or into hydrogels composed of 3% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone), as innovative strategy to improve the biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (Pranoprofen, PF) for topical application. The purpose of this approach has been to increase the contact of PF with the skin, improve its retention in deeper layers, thus enhancing its anti-inflammatory and analgesic effects. The physicochemical characterization of the developed hydrogels showed a non-Newtonian behaviour, typical of semi-solid formulations for skin administration, with sustained release profile. The results obtained from ex vivo skin human permeation and in vivo anti-inflammatory efficacy studies suggest that topical application of HG_PF-F2NPs has been more effective in the treatment of oedema on the skin' surface in comparison to other hydrogels. No signs of skin irritancy have been detected for all the semi-solid formulations containing 0% or 3% azone.

  19. van der Waals force-induced loading of proangiogenic nanoparticles on microbubbles for enhanced neovascularization

    NASA Astrophysics Data System (ADS)

    Chen, Jinrong; Lee, Min Kyung; Qin, Ellen; Misra, Sanjay; Kong, Hyunjoon

    2015-10-01

    Nanoparticles emerged as carriers of promising diagnostic and therapeutic molecules due to their unique size, injectability, and potential to sustainably release molecular cargos. However, with local injection of particles into target tissue, the significant particle loss caused by external biomechanical forces is a great challenge yet to be resolved to date. We hypothesized that nanoparticles associated with tissue-adherent microbubbles in the form of core-shell particles due to van der Waals attractive forces would stably remain on an implanted site and significantly increase therapeutic efficacy of drug cargos. To examine this hypothesis, we used 100 nm diameter nanoparticles made of poly(lactide-co-glycolic acid) (PLGA) as a model nanoparticle and 50 μm diameter microbubbles made of poly(2-hydroxyethyl aspartamide) (PHEA) grafted with octadecyl chains, PHEA-g-C18, as a model microbubble. Simple mixing of PLGA nanoparticles and PHEA-g-C18 microbubbles resulted in the core-shell particles. Following implantation, the PHEA-g-C18 microbubbles acted as glue to minimize the displacement of PLGA nanoparticles, because of the association between the octadecyl chains on PHEA-g-C18 and the epithelium of the tissue. As a consequence, the core-shell particles prepared with Angiopoietin-1 (Ang1)-encapsulated PLGA nanoparticles significantly promoted vascularization in the implanted tissue. Overall, the results of this study provide a simple but advanced strategy for improving therapeutic efficacy of drug-carrying nanoparticles without altering their surface chemistry and potential.Nanoparticles emerged as carriers of promising diagnostic and therapeutic molecules due to their unique size, injectability, and potential to sustainably release molecular cargos. However, with local injection of particles into target tissue, the significant particle loss caused by external biomechanical forces is a great challenge yet to be resolved to date. We hypothesized that nanoparticles

  20. Preparation and characterization of gadolinium-loaded PLGA particles surface modified with RGDS for the detection of thrombus

    PubMed Central

    Zhang, Yu; Zhou, Jun; Guo, Dajing; Ao, Meng; Zheng, Yuanyi; Wang, Zhigang

    2013-01-01

    Thrombotic disease is a leading cause of death and disability worldwide. The development of magnetic resonance molecular imaging provides potential promise for early disease diagnosis. In this study, we explore the preparation and characterization of gadolinium (Gd)-loaded poly (lactic-co-glycolic acid) (PLGA) particles surface modified with the Arg-Gly-Asp-Ser (RGDS) peptide for the detection of thrombus. PLGA was employed as the carrier-delivery system, and a double emulsion solvent-evaporation method (water in oil in water) was used to prepare PLGA particles encapsulating the magnetic resonance contrast agent Gd diethylenetriaminepentaacetic acid (DTPA). To synthesize the Gd-PLGA/chitosan (CS)-RGDS particles, carbodiimide-mediated amide bond formation was used to graft the RGDS peptide to CS to form a CS-RGDS film that coated the surface of the PLGA particles. Blank PLGA, Gd-PLGA, and Gd-PLGA/CS particles were fabricated using the same water in oil in water method. Our results indicated that the RGDS peptide successfully coated the surface of the Gd-PLGA/CS-RGDS particles. The particles had a regular shape, smooth surface, relatively uniform size, and did not aggregate. The high electron density of the Gd-loaded particles and a translucent film around the particles coated with the CS and CS-RGDS films could be observed by transmission electron microscopy. In vitro experiments demonstrated that the Gd-PLGA/CS-RGDS particles could target thrombi and could be imaged using a clinical magnetic resonance scanner. Compared with the Gd-DTPA solution, the longitudinal relaxation time of the Gd-loaded particles was slightly longer, and as the Gd-load concentration increased, the longitudinal relaxation time values decreased. These results suggest the potential of the Gd-PLGA/CS-RGDS particles for the sensitive and specific detection of thrombus at the molecular level. PMID:24124363

  1. Solid Lipid Nanoparticles Loaded with Retinoic Acid and Lauric Acid as an Alternative for Topical Treatment of Acne Vulgaris.

    PubMed

    Silva, Elton Luiz; Carneiro, Guilherme; De Araújo, Lidiane Advíncula; Trindade, Mariana de Jesus Vaz; Yoshida, Maria Irene; Oréfice, Rodrigo Lambert; Farias, Luis de Macêdo; De Carvalho, Maria Auxiliadora Roque; Dos Santos, Simone Gonçalves; Goulart, Gisele Assis Castro; Alves, Ricardo José; Ferreira, Lucas Antônio Miranda

    2015-01-01

    Topical therapy is the first choice for the treatment of mild to moderate acne and all-trans retinoic acid is one of the most used drugs. The combination of retinoids and antimicrobials is an innovative approach for acne therapy. Recently, lauric acid, a saturated fatty acid, has shown strong antimicrobial activity against Propionibacterium acnes. However, topical application of retinoic acid is followed by high incidence of side-effects, including erythema and irritation. Solid lipid nanoparticles represent an alternative to overcome these side-effects. This work aims to develop solid lipid nanoparticles loaded with retinoic acid and lauric acid and evaluate their antibacterial activity. The influence of lipophilic stearylamine on the characteristics of solid lipid nanoparticles was investigated. Solid lipid nanoparticles were characterized for size, zeta potential, encapsulation efficiency, differential scanning calorimetry and X-ray diffraction. The in vitro inhibitory activity of retinoic acid-lauric acid-loaded solid lipid nanoparticles was evaluated against Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis. High encapsulation efficiency was obtained at initial time (94 ± 7% and 100 ± 4% for retinoic acid and lauric acid, respectively) and it was demonstrated that lauric acid-loaded-solid lipid nanoparticles provided the incorporation of retinoic acid. However, the presence of stearylamine is necessary to ensure stability of encapsulation. Moreover, retinoic acid-lauric acid-loaded solid lipid nanoparticles showed growth inhibitory activity against Staphylococcus epidermidis, Propionibacterium acnes and Staphylococcus aureus, representing an interesting alternative for the topical therapy of acne vulgaris.

  2. Assessment of PLGA-PEG-PLGA copolymer hydrogel for sustained drug delivery in the ear.

    PubMed

    Feng, Liang; Ward, Jonette A; Li, S Kevin; Tolia, Gaurav; Hao, Jinsong; Choo, Daniel I

    2014-01-01

    Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEGPLGA upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study, the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and could provide sustained release that could be controlled by using the additives for inner ear applications.

  3. Bone induction by biomimetic PLGA-(PEG-ASP)n copolymer loaded with a novel synthetic BMP-2-related peptide in vitro and in vivo.

    PubMed

    Lin, Zhen-Yu; Duan, Zhi-Xia; Guo, Xiao-Dong; Li, Jing-Feng; Lu, Hong-Wei; Zheng, Qi-Xin; Quan, Da-Ping; Yang, Shu-Hua

    2010-06-01

    BMP-2 is one of the most important growth factors of bone regeneration. Polylactide-co-glycolic acid (PLGA), which is used as a biodegradable scaffold for delivering therapeutic agents, has been intensively investigated. In previous studies, we synthesized a novel BMP-2-related peptide (designated P24) and found that it could enhance the osteoblastic differentiation of bone marrow stromal cells (BMSCs). The objective of this study was to construct a biomimetic composite by incorporating P24 into a modified PLGA-(PEG-ASP)n copolymer to promote bone formation. In vitro, our results demonstrated that PLGA-(PEG-ASP)n scaffolds were shown to be an efficient system for sustained release of P24. Significantly more BMSCs attached to the P24/PLGA-(PEG-ASP)n and PLGA-(PEG-ASP)n membranes than to PLGA, and the cells in the two groups subsequently proliferated more vigorously than those in the PLGA group. The expression of osteogenic markers in P24/PLGA-(PEG-ASP)n group was stronger than that in the PLGA-(PEG-ASP)n and PLGA groups. Radiographic and histological examination, Western blotting and RT-PCR showed that P24/PLGA-(PEG-ASP)n scaffold could induce more effective ectopic bone formation in vivo, as compared with PLGA-(PEG-ASP)n or gelatin sponge alone. It is concluded that the PLGA-(PEG-ASP)n copolymer is a good P24 carrier and can serve as a good scaffold for controlled release of P24. This novel P24/PLGA-(PEG-ASP)n composite promises to be an excellent biomaterial for inducing bone regeneration.

  4. ''Pulling'' Nanoparticles into Water: Phase Transfer of Oleic Acid Stabilized Monodisperse Nanoparticles into Aqueous Solutions of alpha-Cyclodextrin

    SciTech Connect

    Wang, Y.; Wong, J.F.; Teng, X.; Lin, X.Z.; Yang, H.

    2003-10-18

    (B204)This paper describes a general method to drastically improve the disparity of oleic acid stabilized nanoparticles in aqueous solutions. We use oleic acid stabilized monodisperse nanoparticles of iron oxides and silver as model systems, and have modified the surface properties of these nanoparticles through the formation of an inclusion complex between surface-bound surfactant molecules and alpha-cyclodextrin (alpha-CD). After the modification, the nanoparticles of both iron oxide and Ag can transfer from hydrophobic solvents, such as hexane, to alpha-CD aqueous phase. The efficiency of the phase transfer to the aqueous solutions depend son the initial alpha-CD concentration. The alpha-CD/oleic acid complex stabilized nanoparticles can be stable for long periods of time in aqueous phase under ambient atmospheric conditions. Transmission electron microscopy (TME), ultraviolet-visible (UV-vis) spectroscopy, Fourier transform-infrared (FT-IR) spectroscopy, and colorimetric methods have been used in the characterization of these nanoparticles.

  5. A modified double-emulsion method for the preparation of daunorubicin-loaded polymeric nanoparticle with enhanced in vitro anti-tumor activity.

    PubMed

    Liu, Jie; Qiu, Zhiye; Wang, Shenqi; Zhou, Lei; Zhang, Shengmin

    2010-12-01

    The encapsulation of hydrophilic drug in polymeric nanoparticles with high loading remains a challenge due to the rapid penetration of the drug to the external aqueous phase. In order to improve the encapsulation efficiency of daunorubicin (DNR) in poly(D,L-lactic-co-glycolic acid (PLGA) and poly(D,L-lactic acid) (PDLLA) nanoparticles, we fabricated a series of DNR-loaded nanoparticles using a modified double-emulsion solvent evaporation/diffusion method, which introduced a partially water-soluble organic solvent into the particle formation. The influence of various preparation parameters was investigated systematically, such as the ratio of organic solvent, the type of surfactant, the type of polymers and the molecular weight. Results showed that regular spherical PLGA nanoparticles with diameters of 200-300 nm could be produced with a remarkably high DNR encapsulation efficiency (>80%) and loading (6.5% (w/w)). Upon encapsulation, the sustained release of DNR could be controlled over 2 weeks. The results of FT-IR and DSC analysis indicated that the encapsulated DNR in polymeric nanoparticles was inclusion, not absorption. Furthermore, optimized DNR/PLGA nanoparticles showed a significant enhancement of cellular uptake, higher cytotoxicity against HL-60 cells compared with free DNR. These results were potentially useful for the nanoparticle formulation of hydrophilic chemotherapeutic drugs that require efficient delivery to cancer cells as well as sustained release at the specific site.

  6. 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.

  7. Multifunctional nanovehicles for combined 5-fluorouracil and gold nanoparticles based on the nanoprecipitation method.

    PubMed

    Karmi, Abeer; Husseini, Ghaleb A; Faroun, Maryam; Sowwan, Mukhles

    2011-06-01

    To facilitate the administration of combined 5-Fluorouracil (5-FU) and gold nanoparticles (for photothermal treatment purposes), we developed 5-FU-gold-poly(lactide-co-glycolic acid) (5-FU-Au-PLGA) nanovehicles, via the nanoprecipitation method. The gold nanoparticles were incorporated inside the 5-FU-PLGA carriers using a roller mixer. Morphological analysis using atomic force microscopy (AFM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), indicated uniform, singly separated spherical nanoparticles (NPs). Drug content, recovery and entrapment in the NPs were approximated using UV-spectrophotometer data. Approximately 26% of nanoparticles were recovered after drying. The percentage of total drug content was about 30%, and the percentage of drug entrapment reached 57%. Electrostatic Force Microscopy images confirmed the presence of gold inside the drug-loaded nanoparticles. We speculate that the 20-nm gold particles were able to diffuse, after 12 hours of mixing (using the roller mixer), into the PLGA matrix through the 100-nm pores (observed by SEM) without affecting the integrity of the drug delivery vehicle. These synthesized nanoparticles show promise as multimodal vehicles in the delivery of chemotherapeutic agents.