POE/PLGA composite microspheres: formation and in vitro behavior of double walled microspheres.

PubMed

Yang, Yi-Yan; Shi, Meng; Goh, Suat-Hong; Moochhala, Shabbir M; Ng, Steve; Heller, Jorge

2003-03-07

The poly(ortho ester) (POE) and poly(D,L-lactide-co-glycolide) 50:50 (PLGA) composite microspheres were fabricated by a water-in-oil-in-water (w/o/w) double emulsion process. The morphology of the composite microspheres varied depending on POE content. When the POE content was 50, 60 or 70% in weight, the double walled microspheres with a dense core of POE and a porous shell of PLGA were formed. The formation of the double walled POE/PLGA microspheres was analysed. Their in vitro degradation behavior was characterized by scanning electron microscopy, gel permeation chromatography, Fourier-transform infrared microscopy and nuclear magnetic resonance spectroscopy (NMR). It was found that compared to the neat POE or PLGA microspheres, distinct degradation mechanism was achieved in the double walled POE/PLGA microspheres system. The degradation of the POE core was accelerated due to the acidic microenvironment produced by the hydrolysis of the outer PLGA layer. The formation of hollow microspheres became pronounced after the first week in vitro. 1H NMR spectra showed that the POE core was completely degraded after 4 weeks. On the other hand, the outer PLGA layer experienced slightly retarded degradation after the POE core disappeared. PLGA in the double walled microspheres kept more than 32% of its initial molecular weight over a period of 7 weeks.

Insulin-loaded biodegradable PLGA microcapsules: initial burst release controlled by hydrophilic additives.

PubMed

Yamaguchi, Y; Takenaga, M; Kitagawa, A; Ogawa, Y; Mizushima, Y; Igarashi, R

2002-06-17

We investigated the controlled release of human insulin at an initial stage from poly(DL-lactic-co-glycolic acid) (PLGA, M(w) 6600) spherical matrices. PLGA microcapsules were prepared by the novel solvent evaporation multiple emulsion process. When the crystalline insulin was dispersed in dichloromethane as solid-in-oil (S/O) dispersion, it was found that most of insulin molecules were inlaid on the surface of PLGA microcapsules. Consequently, insulin-loaded PLGA microcapsules exhibited marked rapid release of insulin within several hours in both in vivo and in vitro experiments. On the other hand, the addition of glycerol or water in the primary dichloromethane dispersion results in drastically suppressed initial release. It was found by SEM observation that water- or glycerol-in-oil (W/O or G/O) type mini-emulsion droplets with a mean diameter of 300-500 nm were formed in this primary solution. This phenomenon can be theoretically presumed to occur because insulin and PLGA molecules, having amphiphilic properties, converge on the interface between the hydrophilic additive and dichloromethane. Hence, insulin molecules heterogeneously located in the inside of PLGA microcapsules, not on the surface, would be gradually released with PLGA hydrolytic decomposition. As an additional effect of glycerol, the initial burst was further suppressed due to the decrease of the glass transition temperature of PLGA from 42.5 to 36.7 degrees C. Since the annealing of PLGA molecules took place at around 37 degrees C, the porous structure of microspheres immediately disappeared after immersion in PBS or subcutaneous administration. The insulin diffusion through the water-filled pores would be effectively prevented. The strict controlled initial release of insulin from the PLGA microsphere suggested the possibility of utilization in insulin therapy for type I diabetic patients who need construction of a basal insulin profile.

PLGA-PEG-PLGA hydrogel for ocular drug delivery of dexamethasone acetate.

PubMed

Gao, Yuan; Sun, Yan; Ren, Fuzheng; Gao, Shen

2010-10-01

This study aims to investigate the suitability of thermosensitive triblock polymer poly-(DL-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA as a matrix material for ocular delivery of dexamethasone acetate (DXA). The copolymer was synthesized and evaluated for its thermosensitive and gelation properties. DXA in situ gel-forming solution based on PLGA-PEG-PLGA copolymer of 20% (w/w) was prepared and evaluated for ocular pharmacokinetics in rabbit according to the microdialysis method, which was compared to the normal eye drop. The copolymer with 20% (w/w) had a low critical solution temperature of 32 degrees C, which is close to the surface temperature of the eye. The C(max) of DXA in the anterior chamber for the PLGA-PEG-PLGA solution was 125.2 microg/mL, which is sevenfold higher than that of the eye drop, along with greater area under the concentration-time curves (AUC). These results suggest that the PLGA-PEG-PLGA copolymer is potential thermosensitive in situ gel-forming material for ocular drug delivery, and it may improve the bioavailability, efficacy of some eye drugs.

Assessment of PLGA-PEG-PLGA Copolymer Hydrogel for Sustained Drug Delivery in the Ear

PubMed Central

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-PEG-PLGA 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. PMID:24438444

Localised controlled release of simvastatin from porous chitosan-gelatin scaffolds engrafted with simvastatin loaded PLGA-microparticles for bone tissue engineering application.

PubMed

Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Daly, Jacqueline; Chiono, Valeria; Mattu, Clara; Tonda-Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

2016-02-01

Localised controlled release of simvastatin from porous freeze-dried chitosan-gelatin (CH-G) scaffolds was investigated by incorporating simvastatin loaded poly-(dl-lactide-co-glycolide) acid (PLGA) microparticles (MSIMs) into the scaffolds. MSIMs at 10% w/w simvastatin loading were prepared using a single emulsion-solvent evaporation method. The MSIM optimal amount to be incorporated into the scaffolds was selected by analysing the effect of embedding increasing amounts of blank PLGA microparticles (BL-MPs) on the scaffold physical properties and on the in vitro cell viability using a clonal human osteoblastic cell line (hFOB). Increasing the BL-MP content from 0% to 33.3% w/w showed a significant decrease in swelling degree (from 1245±56% to 570±35%). Scaffold pore size and distribution changed significantly as a function of BL-MP loading. Compressive modulus of scaffolds increased with increasing BL-MP amount up to 16.6% w/w (23.0±1.0kPa). No significant difference in cell viability was observed with increasing BL-MP loading. Based on these results, a content of 16.6% w/w MSIM particles was incorporated successfully in CH-G scaffolds, showing a controlled localised release of simvastatin able to influence the hFOB cell proliferation and the osteoblastic differentiation after 11 days. Copyright © 2015 Elsevier B.V. All rights reserved.

[Design and biological evaluation of poly-lactic-co-glycolic acid (PLGA) mesh/collagen-chitosan hybrid scaffold (CCS) as a dermal substitute].

PubMed

Wang, Xin-Gang; You, Chuan-Gang; Sun, Hua-Feng; Hu, Xin-Lei; Han, Chun-Mao; Zhang, Li-Ping; Zheng, Yu-Rong; Li, Qi-Yin

2011-02-01

To design and construct a kind of dermal regeneration template with mesh, and to preliminarily evaluate its biological characteristics. PLGA mesh was integrated into CCS with freeze-drying method for constructing PLGA mesh/CCS composite (PCCS). The micromorphologies and mechanical properties among PLGA mesh, CCS, and PCCS were compared. PCCS and CCS was respectively implanted into subcutaneous tissue of SD rats (PCCS and CCS groups, 9 rats in each group). The tissue samples were collected at post operation week (POW) 1, 2, and 4 for histopathological and immunohistochemical observation. Protein levels of CD68, MPO, IL-1beta, IL-10 were examined by Western blot, with expression of gray value. Data were processed with one-way analysis of variance and t test. Three-dimensional porous structure of PCCS was similar to that of CCS. Mechanical property of PLGA mesh and PCCS was respectively (3.07 +/- 0.10), (3.26 +/- 0.15) MPa, and they were higher than that of CCS [(0.42 +/- 0.21) MPa, F = 592.3, P < 0.0001)]. The scaffolds were filled with newly formed tissue in PCCS group at POW 2, while those in CCS group were observed at POW 4. A large accumulation of macrophages was observed in both groups, especially at POW 2, and more macrophage infiltration was observed in CCS group. The protein level of IL-10 in PCCS group at POW 2 was obviously higher than that in CCS group, while the protein levels of CD68, MPO, IL-1beta were significantly decreased as compared with those in CCS group (with t value from -4.06 to 2.89, P < 0.05 or P < 0.01). PCCS has excellent mechanical property with appropriate three-dimensional porous structure. Meanwhile, it can rapidly induce formation of new tissue and vascularization, and it has a prospect of serving as a dermal substitute.

Enhancement of VEGF-Mediated Angiogenesis by 2-N,6-O-Sulfated Chitosan-Coated Hierarchical PLGA Scaffolds.

PubMed

Yu, Yuanman; Chen, Jie; Chen, Rui; Cao, Lingyan; Tang, Wei; Lin, Dan; Wang, Jing; Liu, Changsheng

2015-05-13

Rapid and controlled vascularization within scaffolds remains one of the key limitations in tissue engineering applications. This study describes the fabrication and characterization of 2-N,6-O-sulfated chitosan (26SCS)-coated hierarchical scaffold composed of poly(lactic-co-glycolic acid) (PLGA) microspheres, as a desirable vehicle for vascular endothelial growth factor (VEGF) delivery and consequent angiogenic boosting in vitro. Owing to the hierarchical porous structure and high affinity between VEGF and 26SCS, the 26SCS-modified PLGA (S-PLGA) scaffold possesses excellent entrapment and sustained release of VEGF. Using human umbilical vein endothelial cells (HUVECs) as a cell model, the VEGF-loaded S-PLGA scaffold shows desirable cell viability and attachment. The bioactivity of released VEGF is validated by intracellular nitric oxide secretion and capillary tube formation, demonstrating the improved capacity of VEGF-mediated pro-angiogenesis ascribed to 26SCS incorporation. Such a strategy will afford an effective method to prepare a scaffold with promoted angiogenesis.

Effect of medium-chain triglycerides on the release behavior of Endostar encapsulated PLGA microspheres.

PubMed

Meng, Boyu; Li, Ling; Hua, Su; Wang, Qingsong; Liu, Chunhui; Xu, Xiangyang; Yin, Xiaojin

2010-09-15

The incomplete release of Endostar from PLGA microspheres was observed in our previous study. In the present study, we focused on the effect of medium-chain triglycerides (MCT) on the in vitro/in vivo release behavior of Endostar encapsulated PLGA microspheres, which were prepared by a water-in-oil-in-water (W/O/W) double-emulsion method with or without MCT. The in vitro accumulated release of Endostar from microspheres co-encapsulated with 30% MCT was found to be 79.04% after a 30-day incubation period in PBS (pH 7.4) at 37 degrees C. However, the accumulated release of Endostar from MCT-free microspheres was found to be only 32.22%. Pouches containing Endostar encapsulated PLGA microspheres were implanted subcutaneously in rats. The effect of MCT on the in vivo release showed a similar trend to the in vitro release. After 30 days, only 9.87% of the total encapsulated Endostar was retained in microspheres co-encapsulated with 30% MCT, while 42.25% of Endostar was retained in MCT-free microspheres. The co-encapsulation of MCT provided the microspheres with a porous surface, which significantly improved the in vitro/in vivo release of Endostar from PLGA microspheres. In addition, in vitro experiments showed that MCT co-encapsulated PLGA microspheres had more inter-connected pores, faster degradation of PLGA, and faster swelling of microspheres, which helped to explain the mechanism of the effect of MCT on improving the release of Endostar from PLGA microspheres. Copyright 2010 Elsevier B.V. All rights reserved.

Cell-adhesive RGD peptide-displaying M13 bacteriophage/PLGA nanofiber matrices for growth of fibroblasts.

PubMed

Shin, Yong Cheol; Lee, Jong Ho; Jin, Linhua; Kim, Min Jeong; Oh, Jin-Woo; Kim, Tai Wan; Han, Dong-Wook

2014-01-01

M13 bacteriophages can be readily fabricated as nanofibers due to non-toxic bacterial virus with a nanofiber-like shape. In the present study, we prepared hybrid nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 bacteriophages which were genetically modified to display the RGD peptide on their surface (RGD-M13 phage). The surface morphology and chemical composition of hybrid nanofiber matrices were characterized by scanning electron microscopy (SEM) and Raman spectroscopy, respectively. Immunofluorescence staining was conducted to investigate the existence of M13 bacteriophages in RGD-M13 phage/PLGA hybrid nanofibers. In addition, the attachment and proliferation of three different types of fibroblasts on RGD-M13 phage/PLGA nanofiber matrices were evaluated to explore how fibroblasts interact with these matrices. SEM images showed that RGD-M13 phage/PLGA hybrid matrices had the non-woven porous structure, quite similar to that of natural extracellular matrices, having an average fiber diameter of about 190 nm. Immunofluorescence images and Raman spectra revealed that RGD-M13 phages were homogeneously distributed in entire matrices. Moreover, the attachment and proliferation of fibroblasts cultured on RGD-M13 phage/PLGA matrices were significantly enhanced due to enriched RGD moieties on hybrid matrices. These results suggest that RGD-M13 phage/PLGA matrices can be efficiently used as biomimetic scaffolds for tissue engineering applications.

Fabrication of mineralized electrospun PLGA and PLGA/gelatin nanofibers and their potential in bone tissue engineering.

PubMed

Meng, Z X; Li, H F; Sun, Z Z; Zheng, W; Zheng, Y F

2013-03-01

Surface mineralization is an effective method to produce calcium phosphate apatite coating on the surface of bone tissue scaffold which could create an osteophilic environment similar to the natural extracellular matrix for bone cells. In this study, we prepared mineralized poly(D,L-lactide-co-glycolide) (PLGA) and PLGA/gelatin electrospun nanofibers via depositing calcium phosphate apatite coating on the surface of these nanofibers to fabricate bone tissue engineering scaffolds by concentrated simulated body fluid method, supersaturated calcification solution method and alternate soaking method. The apatite products were characterized by the scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), and X-ray diffractometry (XRD) methods. A large amount of calcium phosphate apatite composed of dicalcium phosphate dihydrate (DCPD), hydroxyapatite (HA) and octacalcium phosphate (OCP) was deposited on the surface of resulting nanofibers in short times via three mineralizing methods. A larger amount of calcium phosphate was deposited on the surface of PLGA/gelatin nanofibers rather than PLGA nanofibers because gelatin acted as nucleation center for the formation of calcium phosphate. The cell culture experiments revealed that the difference of morphology and components of calcium phosphate apatite did not show much influence on the cell adhesion, proliferation and activity. Copyright © 2012 Elsevier B.V. All rights reserved.

A novel strategy for the preparation of porous microspheres and its application in peptide drug loading.

PubMed

Wei, Yi; Wang, Yuxia; Zhang, Huixia; Zhou, Weiqing; Ma, Guanghui

2016-09-15

A new strategy is developed to prepare porous microspheres with narrow size distribution for peptides controlled release, involving a fabrication of porous microspheres without any porogens followed by a pore closing process. Amphiphilic polymers with different hydrophobic segments (poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA), poly(monomethoxypolyethylene glycol-co-d,l-lactic-co-glycolic acid) (mPEG-PLGA)) are employed as microspheres matrix to prepare porous microspheres based on a double emulsion-premix membrane emulsification technique combined with a solvent evaporation method. Both microspheres possess narrow size distribution and porous surface, which are mainly caused by (a) hydrophilic polyethylene glycol (PEG) segments absorbing water molecules followed by a water evaporation process and (b) local explosion of microspheres due to fast evaporation of dichloromethane (MC). Importantly, mPEG-PLGA microspheres have a honeycomb like structure while mPEG-PLA microspheres have a solid structure internally, illustrating that the different hydrophobic segments could modulate the affinity between solvent and matrix polymer and influence the phase separation rate of microspheres matrix. Long term release patterns are demonstrated with pore-closed microspheres, which are prepared from mPEG-PLGA microspheres loading salmon calcitonin (SCT). These results suggest that it is potential to construct porous microspheres for drug sustained release using permanent geometric templates as new porogens. Copyright © 2016 Elsevier Inc. All rights reserved.

Cellular delivery of PEGylated PLGA nanoparticles.

PubMed

Pamujula, Sarala; Hazari, Sidhartha; Bolden, Gevoni; Graves, Richard A; Chinta, Dakshinamurthy Devanga; Dash, Srikanta; Kishore, Vimal; Mandal, Tarun K

2012-01-01

The objective of this study was to investigate the efficiency of uptake of PEGylated polylactide-co-gycolide (PLGA) nanoparticles by breast cancer cells. Nanoparticles of PLGA containing various amounts of polyethylene glycol (PEG, 5%-15%) were prepared using a double emulsion solvent evaporation method. The nanoparticles were loaded with coumarin-6 (C6) as a fluorescence marker. The particles were characterized for surface morphology, particle size, zeta potential, and for cellular uptake by 4T1 murine breast cancer cells. Irrespective of the amount of PEG, all formulations yielded smooth spherical particles. However, a comparison of the particle size of various formulations showed bimodal distribution of particles. Each formulation was later passed through a 1.2 µm filter to obtain target size particles (114-335 nm) with zeta potentials ranging from -2.8 mV to -26.2 mV. While PLGA-PEG di-block (15% PEG) formulation showed significantly higher 4T1 cellular uptake than all other formulations, there was no statistical difference in cellular uptake among PLGA, PLGA-PEG-PLGA tri-block (10% PEG), PLGA-PEG di-block (5% PEG) and PLGA-PEG di-block (10% PEG) nanoparticles. These preliminary findings indicated that the nanoparticle formulation prepared with 15% PEGylated PLGA showed maximum cellular uptake due to it having the smallest particle size and lowest zeta potential. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

In vitro degradation and release characteristics of spin coated thin films of PLGA with a “breath figure” morphology

PubMed Central

Ponnusamy, Thiruselvam; Lawson, Louise B.; Freytag, Lucy C.; Blake, Diane A.; Ayyala, Ramesh S.; John, Vijay T.

2012-01-01

Poly (lactic-co-glycolic acid) (PLGA) coatings on implant materials are widely used in controlled drug delivery applications. Typically, such coatings are made with non-porous films. Here, we have synthesized a thin PLGA film coating with a highly ordered microporous structure using a simple and inexpensive water templating “breath figure” technique. A single stage process combining spin coating and breath figure process was used to obtain drug incorporated porous thin films. The films were characterized by scanning electron microscope (SEM) to observe the surface and bulk features of porosity and also, degradation pattern of the films. Moreover, the effect of addition of small amount of poly (ethylene glycol) (PEG) into PLGA was characterized. SEM analysis revealed an ordered array of ~2 µm sized pores on the surface with the average film thickness measured to be 20 µm. The incorporation of hydrophilic poly (ethylene glycol) (PEG) enhances pore structure uniformity and facilitates ingress of water into the structure. A five week in vitro degradation study showed a gradual deterioration of the breath figure pores. During the course of degradation, the surface pore structure deteriorates to initially flatten the surface. This is followed by the formation of new pinprick pores that eventually grow into a macroporous film prior to film breakup. Salicylic acid (highly water soluble) and Ibuprofen (sparingly water soluble) were chosen as model drug compounds to characterize release rates, which are higher in films of the breath figure morphology rather than in non-porous films. The results are of significance in the design of biodegradable films used as coatings to modulate delivery. PMID:23507805

Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.

PubMed

Keohane, Kieran; Brennan, Des; Galvin, Paul; Griffin, Brendan T

2014-06-05

The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Positive effects of cell-free porous PLGA implants and early loading exercise on hyaline cartilage regeneration in rabbits.

PubMed

Chang, Nai-Jen; Lin, Chih-Chan; Shie, Ming-You; Yeh, Ming-Long; Li, Chien-Feng; Liang, Peir-In; Lee, Kuan-Wei; Shen, Pei-Hsun; Chu, Chih-Jou

2015-12-01

The regeneration of hyaline cartilage remains clinically challenging. Here, we evaluated the therapeutic effects of using cell-free porous poly(lactic-co-glycolic acid) (PLGA) graft implants (PGIs) along with early loading exercise to repair a full-thickness osteochondral defect. Rabbits were randomly allocated to a treadmill exercise (TRE) group or a sedentary (SED) group and were prepared as either a PGI model or an empty defect (ED) model. TRE was performed as a short-term loading exercise; SED was physical inactivity in a free cage. The knees were evaluated at 6 and 12 weeks after surgery. At the end of testing, none of the knees developed synovitis, formed osteophytes, or became infected. Macroscopically, the PGI-TRE group regenerated a smooth articular surface, with transparent new hyaline-like tissue soundly integrated with the neighboring cartilage, but the other groups remained distinct at the margins with fibrous or opaque tissues. In a micro-CT analysis, the synthesized bone volume/tissue volume (BV/TV) was significantly higher in the PGI-TRE group, which also had integrating architecture in the regeneration site. The thickness of the trabecular (subchondral) bone was improved in all groups from 6 to 12 weeks. Histologically, remarkable differences in the cartilage regeneration were visible. At week 6, compared with SED groups, the TRE groups manifested modest inflammatory cells with pro-inflammatory cytokines (i.e., TNF-α and IL-6), improved collagen alignment and higher glycosaminoglycan (GAG) content, particularly in the PGI-TRE group. At week 12, the PGI-TRE group had the best regeneration outcomes, showing the formation of hyaline-like cartilage, the development of columnar rounded chondrocytes that expressed enriched levels of collagen type II and GAG, and functionalized trabecular bone with osteocytes. In summary, the combination of implanting cell-free PLGA and performing an early loading exercise can significantly promote the full

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

Progesterone PLGA/mPEG-PLGA Hybrid Nanoparticle Sustained-Release System by Intramuscular Injection.

PubMed

Xie, Bin; Liu, Yang; Guo, Yuting; Zhang, Enbo; Pu, Chenguang; He, Haibing; Yin, Tian; Tang, Xing

2018-02-14

To prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of progesterone (PRG), and evaluate the descending required administration dosage in vivo. PRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil solutions. Nanoparticles (NPs) were formed by the method of nanoemulsion, and the pharmacokinetics of the sustained-release PRG H-NPs in male Sprague dawley (SD) rats were investigated. The rats were randomly divided into four groups, each group received: single dose of PRG H-NPs (14.58 mg/kg, i.m.) and PRG-NPs (14.58 mg/kg, i.m.), repeated dosing for 7 days of PRG-oil (2.08 mg/kg, i.m.) solution (Oil-L) and a higher dosage of PRG-oil (6.24 mg/kg, i.m.) solution (Oil-H), respectively. In the pharmacokinetic test, the PRG H-NPs exhibited a comparatively good sustained-release effect against the PRG-NPs without mPEG-PLGA and PRG-oil solution. The pharmacokinetic parameters of the PRG H-NPs, PRG-NPs, Oil-L and Oil-H were AUC 0-t (ng·h·mL -1 ) 8762.1, 1546.1, 1914.5, and 12,138.9, t 1/2 (h)52.7, 44.1, 8.4 and 44.6 respectively. Owing to the modification of PEG, PRG H-NPs can act as safe delivery platforms for sustained-release of drugs with a lower dosage required.

Incorporation of mesoporous silica nanoparticles into random electrospun PLGA and PLGA/gelatin nanofibrous scaffolds enhances mechanical and cell proliferation properties.

PubMed

Mehrasa, Mohammad; Asadollahi, Mohammad Ali; Nasri-Nasrabadi, Bijan; Ghaedi, Kamran; Salehi, Hossein; Dolatshahi-Pirouz, Alireza; Arpanaei, Ayyoob

2016-09-01

Poly(lactic-co-glycolic acid) (PLGA) and PLGA/gelatin random nanofibrous scaffolds embedded with different amounts of mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. To evaluate the effects of nanoparticles on the scaffolds, physical, chemical, and mechanical properties as well as in vitro degradation behavior of scaffolds were investigated. The mean diameters of nanofibers were 974±68nm for the pure PLGA scaffolds vs 832±70, 764±80, and 486±64 for the PLGA/gelatin, PLGA/10wt% MSNPs, and the PLGA/gelatin/10wt% MSNPs scaffolds, respectively. The results suggested that the incorporation of gelatin and MSNPs into PLGA-based scaffolds enhances the hydrophilicity of scaffolds due to an increase of hydrophilic functional groups on the surface of nanofibers. With porosity examination, it was concluded that the incorporation of MSNPs and gelatin decrease the porosity of scaffolds. Nanoparticles also improved the tensile mechanical properties of scaffolds. Using in vitro degradation analysis, it was shown that the addition of nanoparticles to the nanofibers matrix increases the weight loss percentage of PLGA-based samples, whereas it decreases the weight loss percentage in the PLGA/gelatin composites. Cultivation of rat pheochromocytoma cell line (PC12), as precursor cells of dopaminergic neural cells, on the scaffolds demonstrated that the introduction of MSNPs into PLGA and PLGA/gelatin matrix leads to improved cell attachment and proliferation and enhances cellular processes. Copyright © 2016 Elsevier B.V. All rights reserved.

Poly(lactic-co-glycolic acid)(PLGA)/TiO2 nanotube bioactive composite as a novel scaffold for bone tissue engineering: In vitro and in vivo studies.

PubMed

Eslami, Hossein; Azimi Lisar, Hamidreza; Jafarzadeh Kashi, Tahereh Sadat; Tahriri, Mohammadreza; Ansari, Mojtaba; Rafiei, Tohid; Bastami, Farshid; Shahin-Shamsabadi, Alireza; Mashhadi Abbas, Fatemeh; Tayebi, Lobat

2018-05-01

The aim of this study was to synthesize and characterize novel three-dimensional porous scaffolds made of poly (lactic-co-glycolic acid)/TiO 2 nanotube (TNT) composite microspheres for bone tissue engineering applications. The incorporation of TNT greatly increases mechanical properties of PLGA/TNT microsphere-sintered scaffold. The experimental results exhibit that the PLGA/0.5 wt% TNT scaffold sintered at 100 °C for 3 h showed the best mechanical properties and a proper pore structure for tissue engineering. Biodegradation test ascertained that the weight of both PLGA and PLGA/PLGA/0.5 wt% TiO 2 nanotube composites slightly reduced during the first 4 weeks following immersion in SBF solution. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and alkaline phosphatase activity (ALP activity) results represent increased cell viability for PLGA/0.5%TNT composite scaffold in comparison to the control group. In vivo studies show the amount of bone formation for PLGA/TNT was approximately twice of pure PLGA. Vivid histologic images of the newly generated bone on the implants further supported our test results. Eventually, a mathematical model showed that both PLGA and PLGA/TNT scaffolds' mechanical properties follow an exponential trend with time as their degradation occurs. By a three-dimensional finite element model, a more monotonous distribution of stress was present in the scaffold due to the presence of TNT with a reduction in maximum stress on bone. Copyright © 2018 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Healing kinetics of microneedle-formed pores in PLGA films.

PubMed

Mazzara, J M; Balagna, M A; Thouless, M D; Schwendeman, S P

2013-10-28

The spontaneous healing of aqueous pores in poly(D,L-lactic-co-glycolic acid) (PLGA) drug delivery systems has been identified to play a key role in terminating the burst release of large molecules, and to provide a means for novel aqueous-based microencapsulation. To examine healing of PLGA, pores were created of defined size and depth on the surface of thin PLGA films by stamping with blunt-tip microneedles. Pore dimensions on the micron-scale were relevant to surface pores of common PLGA microspheres and could be easily monitored by light microscopy. Most pores healed reproducibly at temperatures above the glass-transition temperature (T(g)) of the films, with healing times decreasing sharply with increasing temperature according to Williams-Landel-Ferry (WLF) behavior. It is suggested that healing is driven by high surface tension in the films and occurs through viscoelastic creep. Hydrated films healed at lower temperatures than dry films, consistent with a drop in Tg upon polymer hydration. Larger pores took longer to heal than smaller ones, while pores larger than 20 μm did not heal before significant polymer degradation occurred. Films of a less hydrophobic PLGA showed slower healing kinetics, attributed to a weaker surface tension driving force. Deeper pores showed signs of in-plane stress from spin-coating, and either ruptured or only partially healed when incubated wet and dry, respectively. © 2013.

Honeycomb-like PLGA- b-PEG Structure Creation with T-Junction Microdroplets.

PubMed

Gultekinoglu, Merve; Jiang, Xinyue; Bayram, Cem; Ulubayram, Kezban; Edirisinghe, Mohan

2018-06-04

Amphiphilic block copolymers are widely used in science owing to their versatile properties. In this study, amphiphilic block copolymer poly(lactic- co-glycolic acid)- block-poly(ethylene glycol) (PLGA- b-PEG) was used to create microdroplets in a T-junction microfluidic device with a well-defined geometry. To compare interfacial characteristics of microdroplets, dichloromethane (DCM) and chloroform were used to prepare PLGA- b-PEG solution as an oil phase. In the T-junction device, water and oil phases were manipulated at variable flow rates from 50 to 300 μL/min by increments of 50 μL/min. Fabricated microdroplets were directly collected on a glass slide. After a drying period, porous two-dimensional and three-dimensional structures were obtained as honeycomb-like structure. Pore sizes were increased according to increased water/oil flow rate for both DCM and chloroform solutions. Also, it was shown that increasing polymer concentration decreased the pore size of honeycomb-like structures at a constant water/oil flow rate (50:50 μL/min). Additionally, PLGA- b-PEG nanoparticles were also obtained on the struts of honeycomb-like structures according to the water solubility, volatility, and viscosity properties of oil phases, by the aid of Marangoni flow. The resulting structures have a great potential to be used in biomedical applications, especially in drug delivery-related studies, with nanoparticle forming ability and cellular responses in different surface morphologies.

In vitro and in vivo evaluation of calcium phosphate composite scaffolds containing BMP-VEGF loaded PLGA microspheres for the treatment of avascular necrosis of the femoral head.

PubMed

Zhang, Hao-Xuan; Zhang, Xiu-Ping; Xiao, Gui-Yong; Hou, Yong; Cheng, Lei; Si, Meng; Wang, Shuai-Shuai; Li, Yu-Hua; Nie, Lin

2016-03-01

Avascular necrosis of the femoral head (ANFH) is difficult to treat due to high pressure and hypoxia, and reduced levels of growth factors such as bone morphogenetic protein (BMP), and vascular endothelial growth factor (VEGF). We generated a novel calcium phosphate (CPC) composite scaffold, which contains BMP-VEGF-loaded poly-lactic-co-glycolic acid (PLGA) microspheres (BMP-VEGF-PLGA-CPC). The BMP-VEGF-loaded microspheres have an encapsulation efficiency of 89.15% for BMP, and 78.55% for VEGF. The BMP-VEGF-PLGA-CPC scaffold also demonstrated a porosity of 62% with interconnected porous structures, and pore sizes of 219 μm and compressive strength of 6.60 MPa. Additionally, bone marrow mesenchymal stem cells (BMSCs) were seeded on scaffolds in vitro. Further characterization showed that the BMP-VEGF-PLGA-CPC scaffolds were biocompatible and enhanced osteogenesis and angiogenesis in vitro. Using a rabbit model of ANFH, BMP-VEGF-PLGA-CPC scaffolds were implanted into the bone tunnels of core decompression in the femoral head for 6 and 12 weeks. Radiographic and histological analysis demonstrated that the BMP-VEGF-PLGA-CPC scaffolds exhibited good biocompatibility, and osteogenic and angiogenic activity in vivo. These results indicate that the BMP-VEGF-PLGA-CPC scaffold may improve the therapeutic effect of core decompression surgery and be used as a treatment for ANFH. Copyright © 2015 Elsevier B.V. All rights reserved.

Differentiation of Induced Pluripotent Stem Cells to Neural Retinal Precursor Cells on Porous Poly-Lactic-co-Glycolic Acid Scaffolds

PubMed Central

Worthington, Kristan S.; Wiley, Luke A.; Guymon, C. Allan; Salem, Aliasger K.

2016-01-01

Abstract Purpose: Cell replacement therapy for the treatment of retinal degeneration is an increasingly feasible approach, but one that still requires optimization of the transplantation strategy. To this end, various polymer substrates can increase cell survival and integration, although the effect of their pore size on cell behavior, particularly differentiation, has yet to be explored. Methods: Salt crystals of varying known size were used to impart structure to poly(lactic-co-glycolic acid) (PLGA) scaffolds by a salt leaching/solvent evaporation process. Mouse induced pluripotent stem cells (miPSCs) were seeded to the polymer scaffolds and supplemented with retinal differentiation media for up to 2 weeks. Proliferation was measured during the course of 2 weeks, while differentiation was evaluated using cell morphology and expression of early retinal development markers. Results: The salt leaching method of porous PLGA fabrication resulted in amorphous smooth pores. Cells attached to these scaffolds and proliferated, reaching a maximum cell number at 10 days postseeding that was 5 times higher on porous PLGA than on nonporous controls. The morphology of many of these cells, including their formation of neurites, was suggestive of neural phenotypes, while their expression of Sox2, Pax6, and Otx2 indicates early retinal development. Conclusions: The use of porous PLGA scaffolds to differentiate iPSCs to retinal phenotypes is a feasible pretransplantation approach. This adds to an important knowledge base; understanding how developing retinal cells interact with polymer substrates with varying structure is a crucial component of optimizing cell therapy strategies. PMID:26692377

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.

Peptide/protein vaccine delivery system based on PLGA particles.

PubMed

Allahyari, Mojgan; Mohit, Elham

2016-03-03

Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted.

Peptide/protein vaccine delivery system based on PLGA particles

PubMed Central

Allahyari, Mojgan; Mohit, Elham

2016-01-01

abstract Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted. PMID:26513024

PLGA microspheres encapsulating siRNA.

PubMed

De Rosa, Giuseppe; Salzano, Giuseppina

2015-01-01

The therapeutic use of small interfering RNA (siRNA) represents a new and powerful approach to suppress the expression of pathologically genes. However, biopharmaceutical drawbacks, such as short half-life, poor cellular uptake, and unspecific distribution into the body, hamper the development of siRNA-based therapeutics. Poly(lactide-co-glycolide), (PLGA) microspheres can be a useful tool to overcome these issues. siRNA can be encapsulated into the PLGA microspheres, which protects the loaded nucleic acid against the enzymatic degradation. Moreover, PLGA microspheres can be injected directly into the action site, where the siRNA can be released in controlled manner, thus avoiding the need of frequent invasive administrations. The complete biodegradability of PLGA to monomers easily metabolized by the body, and its approval by FDA and EMA for parenteral administration, assure the safety of this copolymer and do not require the removal of the device after the complete drug release. In chapter, a basic protocol for the preparation of PLGA microspheres encapsulating siRNA is described. This protocol is based on a double emulsion/solvent evaporation technique, a well known and easy to reproduce method. This specific protocol has been developed to encapsulate a siRNA anti-TNFα in PLGA microspheres, and it has been designed and optimized to achieve high siRNA encapsulation efficiency and slow siRNA release in vitro. However, it can be extended also to other siRNA as well as other RNA or DNA-based oligonucleotides (miRNA, antisense, decoy, etc.). Depending on the applications, chemical modifications of the backbone and site-specific modification within the siRNA sequences could be required.

Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration

NASA Technical Reports Server (NTRS)

Widmer, M. S.; Gupta, P. K.; Lu, L.; Meszlenyi, R. K.; Evans, G. R.; Brandt, K.; Savel, T.; Gurlek, A.; Patrick, C. W. Jr; Mikos, A. G.;

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.

Novel DiR and SPIO nanoparticles embedded PEG-PLGA nanobubbles as a multimodalimaging contrast agent.

PubMed

Luo, Binhua; Zhang, Huajie; Liu, Xuhan; Rao, Rong; Wu, Yun; Liu, Wei

2015-01-01

Fluorescence dye DiR and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in PEG-PLGA nanobubbles (DiR-SPIO-NBs) were produced using double emulsion method on a membrane of Shirasu porous glass (SPG). The nanobubbles encapsulated with DiR and SPIONs had a liquid core (perfluoropentane) and a PEG-PLGA shell. DiR-SPIO-NBs showed biocompatibility based on MTT cytotoxicity and hemolysis studies. The PFP encapsulated in the nanobubbles experienced phase transition under ultrasonic irradation. Nanobubbles dispersed well in saline over 3 months, and the relaxivity was 127.9 mM(-1)s(-1), suggesting that it could be used as a contrast agent in MRI. The MR and fluorescence images in vivo demonstrated that the signal intensity in the spleen and liver was significantly enhanced with the treatment of nanobubbles. In addition, results of ultrasound images suggested that the nanobubbles had persistent contrast ability. In conclusion, nanobubbles could be utilized as an US/MRI/fluorescence contrast agent.

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

PubMed

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

2014-03-01

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

PLGA/liposome hybrid nanoparticles for short-chain ceramide delivery

PubMed Central

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

2014-01-01

Purpose Rapid premature release of lipophilic drugs from liposomal lipid bilayer to plasma proteins and biological membranes is a challenge for targeted drug delivery. The purpose of this study is to reduce premature release of lipophilic short-chain ceramides by encapsulating ceramides into liposomal aqueous interior with the aid of poly( lactic-coglycolicacid) (PLGA). Methods BODIPY FL labeled ceramide (FL-ceramide) and BODIPY-TR labeled ceramide (TR-ceramide) were encapsulated into carboxy-terminated PLGA nanoparticles. The negatively charged PLGA nanoparticles were then encapsulated into cationic liposomes to obtain PLGA/liposome hybrids. As a control, FL-ceramide and/or TR ceramide co-loaded liposomes without PLGA were prepared. The release of ceramides from PLGA/liposome hybrids and liposomes in rat plasma, cultured MDA-MB-231 cells, and rat blood circulation was compared using fluorescence resonance energy transfer (FRET) between FL-ceramide (donor) and TR-ceramide (acceptor). Results FRET analysis showed that FL-ceramide and TR-ceramide in liposomal lipid bilayer were rapidly released during incubation with rat plasma. In contrast, the FL-ceramide and TR-ceramide in PLGA/liposome hybrids showed extended release. FRET images of cells revealed that ceramides in liposomal bilayer were rapidly transferred to cell membranes. In contrast, ceramides in PLGA/liposome hybrids were internalized into cells with nanoparticles simultaneously. Upon intravenous administration to rats, ceramides encapsulated in liposomal bilayer were completely released in 2 minutes. In contrast, ceramides encapsulated in the PLGA core were retained in PLGA/liposome hybrids for 4 hours. Conclusions The PLGA/liposome hybrid nanoparticles reduced in vitro and in vivo premature release of ceramides and offer a viable platform for targeted delivery of lipophilic drugs. PMID:24065591

Design of smart GE11-PLGA/PEG-PLGA blend nanoparticulate platforms for parenteral administration of hydrophilic macromolecular drugs: synthesis, preparation and in vitro/ex vivo characterization.

PubMed

Colzani, Barbara; Speranza, Giovanna; Dorati, Rossella; Conti, Bice; Modena, Tiziana; Bruni, Giovanna; Zagato, Elisa; Vermeulen, Lotte; Dakwar, George R; Braeckmans, Kevin; Genta, Ida

2016-09-25

Active drug targeting and controlled release of hydrophilic macromolecular drugs represent crucial points in designing efficient polymeric drug delivery nanoplatforms. In the present work EGFR-targeted polylactide-co-glycolide (PLGA) nanoparticles were made by a blend of two different PLGA-based polymers. The first, GE11-PLGA, in which PLGA was functionalized with GE11, a small peptide and EGFR allosteric ligand, able to give nanoparticles selective targeting features. The second polymer was a PEGylated PLGA (PEG-PLGA) aimed at improving nanoparticles hydrophilicity and stealth features. GE11 and GE11-PLGA were custom synthetized through a simple and inexpensive method. The nanoprecipitation technique was exploited for the preparation of polymeric nanoparticles composed by a 1:1weight ratio between GE11-PLGA and PEG-PLGA, obtaining smart nanoplatforms with proper size for parenteral administration (143.9±5.0nm). In vitro cellular uptake in EGFR-overexpressing cell line (A549) demonstrated an active internalization of GE11-functionalized nanoparticles. GE11-PLGA/PEG-PLGA blend nanoparticles were loaded with Myoglobin, a model hydrophilic macromolecule, reaching a good loading (2.42% respect to the theoretical 4.00% w/w) and a prolonged release over 60days. GE11-PLGA/PEG-PLGA blend nanoparticles showed good in vitro stability for 30days in physiological saline solution at 4°C and for 24h in pH 7.4 or pH 5.0 buffer at 37°C respectively, giving indications about potential storage and administration conditions. Furthermore ex vivo stability study in human plasma using fluorescence Single Particle Tracking (fSPT) assessed good GE11-PLGA/PEG-PLGA nanoparticles dimensional stability after 1 and 4h. Thanks to the versatility in polymeric composition and relative tunable nanoparticles features in terms of drug incorporation and release, GE11-PLGA/PEG-PLGA blend NPs can be considered highly promising as smart nanoparticulate platforms for the treatment of diseases

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. © 2015 Wiley Periodicals, Inc.

A PLGA-PEG-PLGA Thermosensitive Gel Enabling Sustained Delivery of Ropivacaine Hydrochloride for Postoperative Pain Relief.

PubMed

Fu, Xudong; Zeng, Huilin; Guo, Jiaping; Liu, Hong; Shi, Zhen; Chen, Huhai; Li, Dezong; Xie, Xiangyang; Kuang, Changchun

2017-01-01

Postoperative pain is a complex physiological response to disease and tissue injury. Moderate-to-severe pain typically occurs within 48 h after surgery. Amino amide local anesthetics are widely applied to manage postoperative pain, and they have high efficacy, a low risk for addiction and limited side effects. However, these anesthetics also have short half-lives, often necessitating continuous injection to obtain satisfactory pain relief. In the current work, we used a poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA (PLGA-PEG-PLGA) temperature-sensitive gel to deliver a local anesthetic, ropivacaine hydrochloride (RP), to prolong its analgesic effect. We investigated the influence of polymer and drug concentration on gelation temperature and the in vitro drug release rate from the temperature-sensitive gel. RP-loaded PLGA-PEG-PLGA solution is a liquid at room temperature and forms a gel at temperatures slightly lower than body temperature. With regard to the gel's drug release rate, 37.5, 51.3 and 72.6% of RP was released at 12, 24 and 48 h, respectively. This in vitro drug release profile conformed to the Higuchi equation. To assess pain control efficacy when using the gel, we evaluated the mechanical paw withdrawal reflex threshold, thermal pain threshold and incision cumulative pain scores in a rat incisional model. The results showed that the anti-pain effect of a single injection of RP-loaded gel at the incision site lasted for 48 h, which is significantly longer than the effect produced by injection of RP solution alone. The use of RP-loaded thermosensitive gels could provide a promising method for managing postoperative pain.

Porous microscaffolds for 3D culture of dental pulp mesenchymal stem cells.

PubMed

Bhuptani, Ronak S; Patravale, Vandana B

2016-12-30

The collective power of stem cells due to their evident advantages is incessantly investigated in regenerative medicine to be the next generation exceptional remedy for tissue regeneration and treatment of diseases. Stem cells are highly sensitive and a 3D culture environment is a requisite for its successful transplantation and integration with tissues. Porous microscaffolds can create a 3D microenvironment for growing stems cells, controlling their fate both in vitro and in vivo. In the present study, interconnected porous PLGA microscaffolds were fabricated, characterized and employed to propagate human dental pulp mesenchymal stem cells (DPMSCs) in vitro. The porous topography was investigated by scanning electron microscopy and the pore size was controlled by fabrication conditions such as the concentration of porogen. DPMSCs were cultured on microscaffolds and were evaluated for their morphology, attachment, proliferation, cell viability via MTT and molecular expression (RT-PCR). DPMSCs were adequately proliferated and adhered over the microscaffolds forming a 3D cell-microscaffold construct. The average number of DPMSCs grown on PLGA microscaffolds was significantly higher than monolayer 2D culture during 5th and 7th day. Moreover, cell viability and gene expression results together corroborated that microscaffolds maintained the viability, stemness and plasticity of the cultured dental pulp mesenchymal stem cells. The novel porous microscaffold developed acts as promising scaffold for 3D culture and survival and transplantation of stem cells for tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

IgA and IgM protein primarily drive plasma corona-induced adhesion reduction of PLGA nanoparticles in human blood flow.

PubMed

Sobczynski, Daniel J; Eniola-Adefeso, Omolola

2017-06-01

The high abundance of immunoglobulins (Igs) in the plasma protein corona on poly(lactic-co-glycolic) acid (PLGA)-based vascular-targeted carriers (VTCs) has previously been shown to reduce their adhesion to activated endothelial cells (aECs) in human blood flow. However, the relative role of individual Ig classes (e.g., IgG, IgA, and IgM) in causing adhesion reduction remains largely unknown. Here, we characterized the influence of specific Ig classes in prescribing the binding efficiency of PLGA nano-sized VTCs in blood flow. Specifically, we evaluated the flow adhesion to aECs of PLGA VTCs with systematic depletion of various Igs in their corona. Adhesion reduction was largely eliminated for PLGA VTCs when all Igs were removed from the corona. Furthermore, re-addition of IgA or IgM to the Igs-depleted corona reinstated the low adhesion of PLGA VTCs, as evidenced by ∼40-70% reduction relative to particles with an Igs-deficient corona. However, re-addition of a high concentration of IgG to the Igs-depleted corona did not cause significant adhesion reduction. Overall, the presented results reveal that PLGA VTC adhesion reduction in blood flows is primarily driven by high adsorption of IgA and IgM in the particle corona. Pre-coating of albumin on PLGA VTCs mitigated the extent of adhesion reduction in plasma for some donors but was largely ineffective in general. Overall, this work may shed light into effective control of protein corona composition, thereby enhancing VTC functionality in vivo for eventual clinical use.

IgA and IgM protein primarily drive plasma corona‐induced adhesion reduction of PLGA nanoparticles in human blood flow

PubMed Central

Sobczynski, Daniel J.

2017-01-01

Abstract The high abundance of immunoglobulins (Igs) in the plasma protein corona on poly(lactic‐co‐glycolic) acid (PLGA)‐based vascular‐targeted carriers (VTCs) has previously been shown to reduce their adhesion to activated endothelial cells (aECs) in human blood flow. However, the relative role of individual Ig classes (e.g., IgG, IgA, and IgM) in causing adhesion reduction remains largely unknown. Here, we characterized the influence of specific Ig classes in prescribing the binding efficiency of PLGA nano‐sized VTCs in blood flow. Specifically, we evaluated the flow adhesion to aECs of PLGA VTCs with systematic depletion of various Igs in their corona. Adhesion reduction was largely eliminated for PLGA VTCs when all Igs were removed from the corona. Furthermore, re‐addition of IgA or IgM to the Igs‐depleted corona reinstated the low adhesion of PLGA VTCs, as evidenced by ∼40–70% reduction relative to particles with an Igs‐deficient corona. However, re‐addition of a high concentration of IgG to the Igs‐depleted corona did not cause significant adhesion reduction. Overall, the presented results reveal that PLGA VTC adhesion reduction in blood flows is primarily driven by high adsorption of IgA and IgM in the particle corona. Pre‐coating of albumin on PLGA VTCs mitigated the extent of adhesion reduction in plasma for some donors but was largely ineffective in general. Overall, this work may shed light into effective control of protein corona composition, thereby enhancing VTC functionality in vivo for eventual clinical use. PMID:28932819

Multi-thread parallel algorithm for reconstructing 3D large-scale porous structures

NASA Astrophysics Data System (ADS)

Ju, Yang; Huang, Yaohui; Zheng, Jiangtao; Qian, Xu; Xie, Heping; Zhao, Xi

2017-04-01

Geomaterials inherently contain many discontinuous, multi-scale, geometrically irregular pores, forming a complex porous structure that governs their mechanical and transport properties. The development of an efficient reconstruction method for representing porous structures can significantly contribute toward providing a better understanding of the governing effects of porous structures on the properties of porous materials. In order to improve the efficiency of reconstructing large-scale porous structures, a multi-thread parallel scheme was incorporated into the simulated annealing reconstruction method. In the method, four correlation functions, which include the two-point probability function, the linear-path functions for the pore phase and the solid phase, and the fractal system function for the solid phase, were employed for better reproduction of the complex well-connected porous structures. In addition, a random sphere packing method and a self-developed pre-conditioning method were incorporated to cast the initial reconstructed model and select independent interchanging pairs for parallel multi-thread calculation, respectively. The accuracy of the proposed algorithm was evaluated by examining the similarity between the reconstructed structure and a prototype in terms of their geometrical, topological, and mechanical properties. Comparisons of the reconstruction efficiency of porous models with various scales indicated that the parallel multi-thread scheme significantly shortened the execution time for reconstruction of a large-scale well-connected porous model compared to a sequential single-thread procedure.

Preclinical Development and In Vivo Efficacy of Ceftiofur-PLGA Microparticles

PubMed Central

Vilos, Cristian; Velasquez, Luis A.; Rodas, Paula I.; Zepeda, Katherine; Bong, Soung-Jae; Herrera, Natalia; Cantin, Mario; Simon, Felipe; Constandil, Luis

2015-01-01

Drug delivery systems based on polymeric microparticles represent an interesting field of development for the treatment of several infectious diseases for humans and animals. In this work, we developed PLGA microparticles loaded with ceftiofur (PLGA-cef), a third- generation cephalosporin that is used exclusively used in animals. PLGA-cef was prepared by the double emulsion w/o/w method, and exhibited a diameter in the range of 1.5–2.2 μm, and a negative ζ potential in the range of -35 to -55 mV. The loading yield of PLGA-cef was ~7% and encapsulation efficiency was approximately 40%. The pharmacokinetic study demonstrated a sustained release profile of ceftiofur for 20 days. PLGA-cef administrated in a single dose was more effective than ceftiofur non-encapsulated in rats challenged with S. Typhimurium. The in vivo toxicological evaluation showed that PLGA-cef did not affect the blood biochemical, hematological and hemostasis parameters. Overall, the PLGA-cef showed slow in vivo release profile, high antibacterial efficacy, and low toxicity. The results obtained supports the safe application of PLGA-cef as sustained release platform in the veterinary industry. PMID:25915043

Gentamicin Sulfate PEG-PLGA/PLGA-H Nanoparticles: Screening Design and Antimicrobial Effect Evaluation toward Clinic Bacterial Isolates

PubMed Central

Dorati, Rossella; DeTrizio, Antonella; Spalla, Melissa; Migliavacca, Roberta; Pagani, Laura; Pisani, Silvia; Chiesa, Enrica; Modena, Tiziana; Genta, Ida

2018-01-01

Nanotechnology is a promising approach both for restoring or enhancing activity of old and conventional antimicrobial agents and for treating intracellular infections by providing intracellular targeting and sustained release of drug inside infected cells. The present paper introduces a formulation study of gentamicin loaded biodegradable nanoparticles (Nps). Solid-oil-in water technique was studied for gentamicin sulfate nanoencapsulation using uncapped Polylactide-co-glycolide (PLGA-H) and Polylactide-co-glycolide-co-Polyethylenglycol (PLGA-PEG) blends. Screening design was applied to optimize: drug payload, Nps size and size distribution, stability and resuspendability after freeze-drying. PLGA-PEG concentration resulted most significant factor influencing particles size and drug content (DC): 8 w/w% DC and 200 nm Nps were obtained. Stirring rate resulted most influencing factor for size distribution (PDI): 700 rpm permitted to obtain homogeneous Nps dispersion (PDI = 1). Further experimental parameters investigated, by 23 screening design, were: polymer blend composition (PLGA-PEG and PLGA-H), Polyvinylalcohol (PVA) and methanol concentrations into aqueous phase. Drug content was increased to 10.5 w/w%. Nanoparticle lyophilization was studied adding cryoprotectants, polyvinypirrolidone K17 and K32, and sodiumcarboxymetylcellulose. Freeze-drying protocol was optimized by a mixture design. A freeze-dried Nps powder free resuspendable with stable Nps size and payload, was developed. The powder was tested on clinic bacterial isolates demonstrating that after encapsulation, gentamicin sulfate kept its activity. PMID:29329209

Large-scale model of flow in heterogeneous and hierarchical porous media

NASA Astrophysics Data System (ADS)

Chabanon, Morgan; Valdés-Parada, Francisco J.; Ochoa-Tapia, J. Alberto; Goyeau, Benoît

2017-11-01

Heterogeneous porous structures are very often encountered in natural environments, bioremediation processes among many others. Reliable models for momentum transport are crucial whenever mass transport or convective heat occurs in these systems. In this work, we derive a large-scale average model for incompressible single-phase flow in heterogeneous and hierarchical soil porous media composed of two distinct porous regions embedding a solid impermeable structure. The model, based on the local mechanical equilibrium assumption between the porous regions, results in a unique momentum transport equation where the global effective permeability naturally depends on the permeabilities at the intermediate mesoscopic scales and therefore includes the complex hierarchical structure of the soil. The associated closure problem is numerically solved for various configurations and properties of the heterogeneous medium. The results clearly show that the effective permeability increases with the volume fraction of the most permeable porous region. It is also shown that the effective permeability is sensitive to the dimensionality spatial arrangement of the porous regions and in particular depends on the contact between the impermeable solid and the two porous regions.

Prevention of adhesion bands by ibuprofen-loaded PLGA nanofibers.

PubMed

Jamshidi-Adegani, Fatemeh; Seyedjafari, Ehsan; Gheibi, Nematollah; Soleimani, Masoud; Sahmani, Mehdi

2016-07-08

In this study, prevention of the adhesion bands and inflammatory features has been investigated using poly (lactic-co-glycolic acid)-ibuprofen (PLGA-IB) nanofibrous meshes in a mice model. To find the optimized membrane for prevention of postoperative adhesion bands, we have compared PLGA-IB group with PLGA, IB, and control groups in a mice adhesion model. Two scoring adhesion systems were used to represent the outcome. According to the results obtained in this study, the PLGA-IB nanofiber membrane showed a greater reduction in adhesion band than other groups. In conclusion, among FDA-approved polymers and drugs, PLGA-IB meshes could be applicable as a potential candidate for prevention of postoperative abdominal inflammation and adhesion bands formation. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:990-997, 2016. © 2016 American Institute of Chemical Engineers.

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.

Stabilization of Tetanus Toxoid Encapsulated in PLGA Microspheres

PubMed Central

Jiang, Wenlei; Schwendeman, Steven P.

2014-01-01

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT) in PLGA microspheres. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: 1) protein aggregation mediated by formaldehyde and 2) acid-induced protein unfolding and epitope damage. Further, we systemically identified excipients which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA. PMID:18710256

Stabilization of tetanus toxoid encapsulated in PLGA microspheres.

PubMed

Jiang, Wenlei; Schwendeman, Steven P

2008-01-01

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine based on PLGA microspheres have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT), in the polymer. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: (1) protein aggregation mediated by formaldehyde and (2) acid-induced protein unfolding and epitope damage. Further, we systematically identified excipients, which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA.

Fabrication of orderly nanostructured PLGA scaffolds using anodic aluminum oxide templates.

PubMed

Wang, Gou-Jen; Lin, Yan-Cheng; Li, Ching-Wen; Hsueh, Cheng-Chih; Hsu, Shan-Hui; Hung, Huey-Shan

2009-08-01

In this research, two simple fabrication methods to fabricate orderly nanostructured PLGA scaffolds using anodic aluminum oxide (AAO) template were conducted. In the vacuum air-extraction approach, the PLGA solution was cast on an AAO template first. The vacuum air-extraction process was then applied to suck the semi-congealed PLGA into the nanopores of the AAO template to form a bamboo sprouts array of PLGA. The surface roughness of the nanostructured scaffolds, ranging from 20 nm to 76 nm, can be controlled by the sucking time of the vacuum air-extraction process. In the replica molding approach, the PLGA solution was cast on the orderly scraggy barrier-layer surface of an AAO membrane to fabricate a PLGA scaffold of concave nanostructure. Cell culture experiments using the bovine endothelial cells (BEC) demonstrated that the nanostructured PLGA membrane can increase the cell growing rate, especially for the bamboo sprouts array scaffolds with smaller surface roughness.

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.

Emulsion Electrospinning as an Approach to Fabricate PLGA/Chitosan Nanofibers for Biomedical Applications

PubMed Central

Tavanai, Hossein; Hilborn, Jöns; Donzel-Gargand, Olivier; Leifer, Klaus; Arpanaei, Ayyoob

2014-01-01

Novel nanofibers from blends of polylactic-co-glycolic acid (PLGA) and chitosan have been produced through an emulsion electrospinning process. The spinning solution employed polyvinyl alcohol (PVA) as the emulsifier. PVA was extracted from the electrospun nanofibers, resulting in a final scaffold consisting of a blend of PLGA and chitosan. The fraction of chitosan in the final electrospun mat was adjusted from 0 to 33%. Analyses by scanning and transmission electron microscopy show uniform nanofibers with homogenous distribution of PLGA and chitosan in their cross section. Infrared spectroscopy verifies that electrospun mats contain both PLGA and chitosan. Moreover, contact angle measurements show that the electrospun PLGA/chitosan mats are more hydrophilic than electrospun mats of pure PLGA. Tensile strengths of 4.94 MPa and 4.21 MPa for PLGA/chitosan in dry and wet conditions, respectively, illustrate that the polyblend mats of PLGA/chitosan are strong enough for many biomedical applications. Cell culture studies suggest that PLGA/chitosan nanofibers promote fibroblast attachment and proliferation compared to PLGA membranes. It can be assumed that the nanofibrous composite scaffold of PLGA/chitosan could be potentially used for skin tissue reconstruction. PMID:24689041

PLGA: a unique polymer for drug delivery.

PubMed

Kapoor, Deepak N; Bhatia, Amit; Kaur, Ripandeep; Sharma, Ruchi; Kaur, Gurvinder; Dhawan, Sanju

2015-01-01

Biodegradable polymers have played an important role in the delivery of drugs in a controlled and targeted manner. Polylactic-co-glycolic acid (PLGA) is one of the extensively researched synthetic biodegradable polymers due to its favorable properties. It is also known as a 'Smart Polymer' due to its stimuli sensitive behavior. A wide range of PLGA-based drug delivery systems have been reported for the treatment or diagnosis of various diseases and disorders. The present review provides an overview of the chemistry, physicochemical properties, biodegradation behavior, evaluation parameters and applications of PLGA in drug delivery. Different drug-polymer combinations developed into drug delivery or carrier systems are enumerated and discussed.

Porous microwells for geometry-selective, large-scale microparticle arrays

NASA Astrophysics Data System (ADS)

Kim, Jae Jung; Bong, Ki Wan; Reátegui, Eduardo; Irimia, Daniel; Doyle, Patrick S.

2017-01-01

Large-scale microparticle arrays (LSMAs) are key for material science and bioengineering applications. However, previous approaches suffer from trade-offs between scalability, precision, specificity and versatility. Here, we present a porous microwell-based approach to create large-scale microparticle arrays with complex motifs. Microparticles are guided to and pushed into microwells by fluid flow through small open pores at the bottom of the porous well arrays. A scaling theory allows for the rational design of LSMAs to sort and array particles on the basis of their size, shape, or modulus. Sequential particle assembly allows for proximal and nested particle arrangements, as well as particle recollection and pattern transfer. We demonstrate the capabilities of the approach by means of three applications: high-throughput single-cell arrays; microenvironment fabrication for neutrophil chemotaxis; and complex, covert tags by the transfer of an upconversion nanocrystal-laden LSMA.

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.

Endocytic pathways involved in PLGA nanoparticle uptake by grapevine cells and role of cell wall and membrane in size selection.

PubMed

Palocci, Cleofe; Valletta, Alessio; Chronopoulou, Laura; Donati, Livia; Bramosanti, Marco; Brasili, Elisa; Baldan, Barbara; Pasqua, Gabriella

2017-12-01

PLGA NPs' cell uptake involves different endocytic pathways. Clathrin-independent endocytosis is the main internalization route. The cell wall plays a more prominent role than the plasma membrane in NPs' size selection. In the last years, many studies on absorption and cell uptake of nanoparticles by plants have been conducted, but the understanding of the internalization mechanisms is still largely unknown. In this study, polydispersed and monodispersed poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs) were synthesized, and a strategy combining the use of transmission electron microscopy (TEM), confocal analysis, fluorescently labeled PLGA NPs, a probe for endocytic vesicles (FM4-64), and endocytosis inhibitors (i.e., wortmannin, ikarugamycin, and salicylic acid) was employed to shed light on PLGA NP cell uptake in grapevine cultured cells and to assess the role of the cell wall and plasma membrane in size selection of PLGA NPs. The ability of PLGA NPs to cross the cell wall and membrane was confirmed by TEM and fluorescence microscopy. A strong adhesion of PLGA NPs to the outer side of the cell wall was observed, presumably due to electrostatic interactions. Confocal microscopy and treatment with endocytosis inhibitors suggested the involvement of both clathrin-dependent and clathrin-independent endocytosis in cell uptake of PLGA NPs and the latter appeared to be the main internalization pathway. Experiments on grapevine protoplasts revealed that the cell wall plays a more prominent role than the plasma membrane in size selection of PLGA NPs. While the cell wall prevents the uptake of PLGA NPs with diameters over 50 nm, the plasma membrane can be crossed by PLGA NPs with a diameter of 500-600 nm.

Active self-healing encapsulation of vaccine antigens in PLGA microspheres

PubMed Central

Desai, Kashappa-Goud H.; Schwendeman, Steven P.

2013-01-01

Herein, we describe the detailed development of a simple and effective method to microencapsulate vaccine antigens in poly(lactic-co-glycolic acid) (PLGA) by simple mixing of preformed active self-microencapsulating (SM) PLGA microspheres in a low concentration aqueous antigen solution at modest temperature (10-38 °C). Co-encapsulating protein-sorbing vaccine adjuvants and polymer plasticizers were used to “actively” load the protein in the polymer pores and facilitate polymer self-healing at temperature > hydrated polymer glass transition temperature, respectively. The microsphere formulation parameters and loading conditions to provide optimal active self-healing microencapsulation of vaccine antigen in PLGA was investigated. Active self-healing encapsulation of two vaccine antigens, ovalbumin and tetanus toxoid (TT), in PLGA microspheres was adjusted by preparing blank microspheres containing different vaccine adjuvant (aluminum hydroxide (Al(OH)3) or calcium phosphate). Active loading of vaccine antigen in Al(OH)3-PLGA microspheres was found to: a) increase proportionally with an increasing loading of Al(OH)3 (0.88-3 wt%) and addition of porosigen, b) decrease when the inner Al(OH)3/trehalose phase to 1 mL outer oil phase and size of microspheres was respectively > 0.2 mL and 63 μm, and c) change negligibly by PLGA concentration and initial incubation (loading) temperature. Encapsulation of protein sorbing Al(OH)3 in PLGA microspheres resulted in suppression of self-healing of PLGA pores, which was then overcome by improving polymer chain mobility, which in turn was accomplished by coincorporating hydrophobic plasticizers in PLGA. Active self-healing microencapsulation of manufacturing process-labile TT in PLGA was found to: a) obviate micronization- and organic solvent-induced TT degradation, b) improve antigen loading (1.4-1.8 wt% TT) and encapsulation efficiency (~ 97%), c) provide nearly homogeneous distribution and stabilization of antigen in polymer

Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles

PubMed Central

Hoti, Ada; Iovene, Pietro Alessandro; Natalello, Antonino; Avvakumova, Svetlana; Colombo, Miriam

2018-01-01

Background We report the development of an efficient antibody delivery system for the incorporation of trastuzumab (TZ) into poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs). The aim of the work was to overcome the current limitations in the clinical use of therapeutic antibodies, including immunogenicity, poor pharmacokinetics, low tumor penetration and safety issues. Materials and methods Trastuzumab-loaded PLGA NPs (PLGA-TZ) were synthesized according to a double emulsion method. The same protocol was used to produce control batches of nonspecific IgG-loaded NPs and empty PLGA NPs. After release of TZ from PLGA NPs, the effects on the main biological activities of the antibody were evaluated on SKBR3 (human epidermal growth factor receptor 2 [HER2]-positive breast cancer cell line), including specific binding to HER2, phosphorylation of HER2 (Y1248), degradation of HER2 protein and antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. In addition, an MTT assay was performed for treating SKBR3 cells with PLGA NPs loaded with TZ and doxorubicin to evaluate the cytotoxic activity of the combined treatment. Results and discussion TZ was gradually released in a prolonged way over 30 days. The physical characterization performed with circular dichroism, Fourier transform infrared and fluorescence spectroscopy of TZ after release demonstrated that no structural alterations occurred compared to the native antibody. In vitro experiments using SKBR3 cells showed that TZ released from PLGA NPs maintained the same biological activity of native TZ. PLGA NPs allowed a good co-encapsulation efficiency of TZ and doxorubicin resulting in improved therapy. Conclusion With the TZ case study, we demonstrate that the distinctive features of therapeutic monoclonal antibodies, including molecular targeting efficiency, capability to inhibit or properly affect the regulatory signaling pathways of cancer cells and stimulation of the ADCC, are fully preserved after loading

Neurotensin-loaded PLGA/CNC composite nanofiber membranes accelerate diabetic wound healing.

PubMed

Zheng, Zhifang; Liu, Yishu; Huang, Wenhua; Mo, Yunfei; Lan, Yong; Guo, Rui; Cheng, Biao

2018-04-13

Diabetic foot ulcers (DFUs) are a threat to human health and can lead to amputation and even death. Recently neurotensin (NT), an inflammatory modulator in wound healing, was found to be beneficial for diabetic wound healing. As we demonstrated previously, polylactide-polyglycolide (PLGA) and cellulose nanocrystals (CNCs) (PLGA/CNC) nanofiber membranes show good cytocompatibility and facilitate fibroblast adhesion, spreading and proliferation. PLGA/CNC nanofiber membranes are novel materials that have not been used previously as NT carriers in diabetic wounds. This study aims to explore the therapeutic efficacy and possible mechanisms of NT-loaded PLGA/CNC nanofiber membranes in full-thickness skin wounds in spontaneously diabetic mice. The results showed that NT could be sustained released from NT-loaded PLGA/CNC composite nanofiber membranes for 2 weeks. NT-loaded PLGA/CNC composite nanofiber membranes induced more rapid healing than other control groups. After NT exposure, the histological scores of the epidermal and dermal regeneration and the ratios of the fibrotic area to the whole area were increased. NT-loaded PLGA/CNC composite nanofiber membranes also decreased the expressions of the inflammatory cytokines IL-1β and IL-6. These results suggest that NT-loaded PLGA/CNC composite nanofiber membranes for sustained delivery of NT should effectively promote tissue regeneration for the treatment of DFUs.

Concepts and practices used to develop functional PLGA-based nanoparticulate systems.

PubMed

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.

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

Production of large-scale, freestanding vanadium pentoxide nanobelt porous structures

NASA Astrophysics Data System (ADS)

Yun, Yong Ju; Kim, Byung Hoon; Hong, Won G.; Kim, Chang Hee; Kim, Yark Yeon; Jeong, Eun-Ju; Jang, Won Ick; Yu, Han Young

2012-02-01

Large-scale, freestanding, porous structures of vanadium pentoxide nanobelts (VPNs) were successfully prepared using the template-free freeze-drying method. The porous and multi-layered VPN macrostructures are composed of randomly oriented long nanobelts (over 100 μm) and their side length can be controlled up to a few tens of centimetres. Also, the bulk density and surface area of these macrostructures are 3-5 mg cm-3 and 40-80 m2 g-1, respectively, which are similar to those of the excellent adsorbents. In addition, the removal efficiency measurements of ammonia molecules revealed that the VPN porous structures can adsorb the ammonia molecules with the combinations of van der Waals forces and strong chemical bonding by functional groups on the VPN surface.

Production of large-scale, freestanding vanadium pentoxide nanobelt porous structures.

PubMed

Yun, Yong Ju; Kim, Byung Hoon; Hong, Won G; Kim, Chang Hee; Kim, Yark Yeon; Jeong, Eun-ju; Jang, Won Ick; Yu, Han Young

2012-03-07

Large-scale, freestanding, porous structures of vanadium pentoxide nanobelts (VPNs) were successfully prepared using the template-free freeze-drying method. The porous and multi-layered VPN macrostructures are composed of randomly oriented long nanobelts (over 100 μm) and their side length can be controlled up to a few tens of centimetres. Also, the bulk density and surface area of these macrostructures are 3-5 mg cm(-3) and 40-80 m(2) g(-1), respectively, which are similar to those of the excellent adsorbents. In addition, the removal efficiency measurements of ammonia molecules revealed that the VPN porous structures can adsorb the ammonia molecules with the combinations of van der Waals forces and strong chemical bonding by functional groups on the VPN surface.

Histological evaluation of osteogenesis of 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds in a rabbit model.

PubMed

Ge, Zigang; Tian, Xianfeng; Heng, Boon Chin; Fan, Victor; Yeo, Jin Fei; Cao, Tong

2009-04-01

Utilizing a suitable combination of lactide and glycolide in a copolymer would optimize the degradation rate of a scaffold upon implantation in situ. Moreover, 3D printing technology enables customizing the shape of the scaffold to biometric data from CT and MRI scans. A previous in vitro study has shown that novel 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds had good biocompatibility and mechanical properties comparable with human cancellous bone, while they could support proliferation and osteogenic differentiation of osteoblasts. Based on the previous study, this study evaluated PLGA scaffolds for bone regeneration within a rabbit model. The scaffolds were implanted at two sites on the same animal, within the periosteum and within bi-cortical bone defects on the iliac crest. Subsequently, the efficacy of bone regeneration within the implanted scaffolds was evaluated at 4, 12 and 24 weeks post-surgery through histological analysis. In both the intra-periosteum and iliac bone defect models, the implanted scaffolds facilitated new bone tissue formation and maturation over the time course of 24 weeks, even though there was initially observed to be little tissue ingrowth within the scaffolds at 4 weeks post-surgery. Hence, the 3D-printed porous PLGA scaffolds investigated in this study displayed good biocompatibility and are osteoconductive in both the intra-periosteum and iliac bone defect models.

Bacterial inhibition potential of 3D rapid-prototyped magnesium-based porous composite scaffolds–an in vitro efficacy study

PubMed Central

Ma, Rui; Lai, Yu-xiao; Li, Long; Tan, Hong-lue; Wang, Jia-li; Li, Ye; Tang, Ting-ting; Qin, Ling

2015-01-01

Bone infections are common in trauma-induced open fractures with bone defects. Therefore, developing anti-infection scaffolds for repairing bone defects is desirable. This study develoepd novel Mg-based porous composite scaffolds with a basal matrix composed of poly(lactic-co-glycolicacid) (PLGA) and tricalcium phosphate (TCP). A unique low-temperature rapid prototyping technology was used to fabricate the scaffolds, including PLGA/TCP (PT), PLGA/TCP/5%Mg (PT5M), PLGA/TCP/10%Mg (PT10M), and PLGA/TCP/15%Mg (PT15M). The bacterial adhesion and biofilm formation of Staphylococcus aureus were evaluated. The results indicated that the Mg-based scaffolds significantly inhibited bacterial adhesion and biofilm formation compared to PT, and the PT10M and PT15M exhibited significantly stronger anti-biofilm ability than PT5M. In vitro degratation tests revealed that the degradation of the Mg-based scaffolds caused an increase of pH, Mg2+ concentration and osmolality, and the increased pH may be one of the major contributing factors to the antibacterial function of the Mg-based scaffolds. Additionally, the PT15M exhibited an inhibitory effect on cell adhesion and proliferation of MC3T3-E1 cells. In conclusion, the PLGA/TCP/Mg scaffolds could inhibit bacterial adhesion and biofilm formation, and the PT10M scaffold was considered to be an effective composition with considerable antibacterial ability and good cytocompatibility. PMID:26346217

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.

Translocator protein ligand-PLGA conjugated nanoparticles for 5-fluorouracil delivery to glioma cancer cells.

PubMed

Laquintana, Valentino; Denora, Nunzio; Lopalco, Antonio; Lopedota, Angela; Cutrignelli, Annalisa; Lasorsa, Francesco Massimo; Agostino, Giulia; Franco, Massimo

2014-03-03

Translocator protein 18 kDa (TSPO) is a promising target for molecular imaging and for targeted drug delivery to tumors overexpressing TSPO. In our previous work, new macromolecular conjugates with a high affinity and selectivity for TSPO were prepared by conjugating the biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) polymer with two potent and selective TSPO ligands, namely, compounds 1 and 2. Based on this, nanoparticle delivery systems (NPs), employing TSPO ligand-PLGA conjugated (PLGA-TSPO) polymers, were prepared. Furthermore, to evaluate the ability of the new NPs to be used as a drug delivery systems for anticancer therapy, PLGA-TSPO NPs were loaded with 5-fluorouracil (5-FU), chosen as a model hydrophilic anticancer drug. The main goal of this work was to investigate the synergistic potential of using NP conjugates PLGA-TSPO, TSPO ligands being pro-apoptotic agents, to simultaneously deliver a cytotoxic anticancer drug. To better highlight the occurrence of synergistic effects, dual drug loaded PLGA NPs (PLGA NPs/5-FU/1) and dual drug loaded PLGA-TSPO NPs (PLGA-TSPO NPs/5-FU/1), with 5-FU and TSPO ligand 1 physically incorporated together, were also prepared and characterized. The particle size and size distribution, surface morphology, and drug encapsulation efficiency, as well as the drug release kinetics, were investigated. In vitro cytotoxicity studies were carried out on C6 glioma cells overexpressing TSPO, and to evaluate the potential uptake of these nanoparticulate systems, the internalization of fluorescent labeled PLGA-TSPO NPs (FITC-PLGA-TSPO NPs) was also investigated by fluorescence microscopy. Results demonstrated that PLGA-TSPO NPs/5-FU and dual drug loaded PLGA NPs/5-FU/1 and PLGA-TSPO NPs/5-FU/1 could significantly enhance toxicity against human cancer cells due to the synergistic effect of the TSPO ligand 1 with the anticancer drug 5-FU.

The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability.

PubMed

Ma, Yiran; Zhao, Xinyi; Li, Jian; Shen, Qi

2012-01-01

The aim of this research was to increase the oral bioavailability of daidzein by the formulations of poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with daidzein. Amongst the various traditional and novel techniques of preparing daidzein-loaded PLGA nanoparticles, daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were selected. The average drug entrapment efficiency, particle size, and zeta potential of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were 81.9% ± 5%, 309.2 ± 14.0 nm, -32.14 ± 2.53 mV and 83.2% ± 7.2%, 323.2 ± 4.8 nm, -18.73 ± 1.68 mV, respectively. The morphological characterization of nanoparticles was observed with scanning electron microscopy by stereological method and the physicochemical state of nanoparticles was valued by differential scanning calorimetry. The in vitro drug-release profile of both nanoparticle formulations fitted the Weibull dynamic equation. Pharmacokinetic studies demonstrated that after oral administration of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 5.57- and 8.85-fold, respectively, compared to daidzein suspension as control. These results describe an effective strategy for oral delivery of daidzein-loaded PLGA nanoparticles and might provide a fresh approach to enhancing the bioavailability of drugs with poor lipophilic and poor hydrophilic properties.

The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability

PubMed Central

Ma, Yiran; Zhao, Xinyi; Li, Jian; Shen, Qi

2012-01-01

The aim of this research was to increase the oral bioavailability of daidzein by the formulations of poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with daidzein. Amongst the various traditional and novel techniques of preparing daidzein-loaded PLGA nanoparticles, daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were selected. The average drug entrapment efficiency, particle size, and zeta potential of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were 81.9% ± 5%, 309.2 ± 14.0 nm, −32.14 ± 2.53 mV and 83.2% ± 7.2%, 323.2 ± 4.8 nm, −18.73 ± 1.68 mV, respectively. The morphological characterization of nanoparticles was observed with scanning electron microscopy by stereological method and the physicochemical state of nanoparticles was valued by differential scanning calorimetry. The in vitro drug-release profile of both nanoparticle formulations fitted the Weibull dynamic equation. Pharmacokinetic studies demonstrated that after oral administration of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 5.57- and 8.85-fold, respectively, compared to daidzein suspension as control. These results describe an effective strategy for oral delivery of daidzein-loaded PLGA nanoparticles and might provide a fresh approach to enhancing the bioavailability of drugs with poor lipophilic and poor hydrophilic properties. PMID:22346351

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. Copyright © 2014 Elsevier B.V. All rights reserved.

PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses.

PubMed

Ma, Wenxue; Chen, Mingshui; Kaushal, Sharmeela; McElroy, Michele; Zhang, Yu; Ozkan, Cengiz; Bouvet, Michael; Kruse, Carol; Grotjahn, Douglas; Ichim, Thomas; Minev, Boris

2012-01-01

The peptide vaccine clinical trials encountered limited success because of difficulties associated with stability and delivery, resulting in inefficient antigen presentation and low response rates in patients with cancer. The purpose of this study was to develop a novel delivery approach for tumor antigenic peptides in order to elicit enhanced immune responses using poly(DL-lactide-co-glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA-NPs were made using the double emulsion-solvent evaporation method. Artificial antigen-presenting cells were generated by human dendritic cells (DCs) loaded with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the antigen presentation was measured by interferon-γ ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96(®) Non-Radioactive Cytotoxicity Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was compared between the methods of emulsification in incomplete Freund's adjuvant and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a mean zeta potential of -15.53 ± 0.71 mV; the PLGA-NPs could be colocalized in human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs encapsulating peptide induced significantly stronger CTL cytotoxicity than those pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a three-peptide cocktail induced a significantly greater CTL response than those encapsulating a two-peptide cocktail. Most importantly, the peptide dose encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete Freund's adjuvant, but it induced a more powerful CTL response in vivo. These results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a promising approach to induce effective antitumor CTL

Comparison of three different methods for effective introduction of platelet-rich plasma on PLGA woven mesh.

PubMed

Lee, Ji-Hye; Nam, Jinwoo; Kim, Hee Joong; Yoo, Jeong Joon

2015-03-11

For successful tissue regeneration, effective cell delivery to defect site is very important. Various types of polymer biomaterials have been developed and applied for effective cell delivery. PLGA (poly lactic-co-glycolic acid), a synthetic polymer, is a commercially available and FDA approved material. Platelet-rich plasma (PRP) is an autologous growth factor cocktail containing various growth factors including PDGF, TGFβ-1 and BMPs, and has shown positive effects on cell behaviors. We hypothesized that PRP pretreatment on PLGA mesh using different methods would cause different patterns of platelet adhesion and stages which would modulate cell adhesion and proliferation on the PLGA mesh. In this study, we pretreated PRP on PLGA using three different methods including simple dripping (SD), dynamic oscillation (DO) and centrifugation (CE), then observed the amount of adhered platelets and their activation stage distribution. The highest amount of platelets was observed on CE mesh and calcium treated CE mesh. Moreover, calcium addition after PRP coating triggered dramatic activation of platelets which showed large and flat morphologies of platelets with rich fibrin networks. Human chondrocytes (hCs) and human bone marrow stromal cells (hBMSCs) were next cultured on PRP-pretreated PLGA meshes using different preparation methods. CE mesh showed a significant increase in the initial cell adhesion of hCs and proliferation of hBMSCs compared with SD and DO meshes. The results demonstrated that the centrifugation method can be considered as a promising coating method to introduce PRP on PLGA polymeric material which could improve cell-material interaction using a simple method.

Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content

PubMed Central

Li, Mingguang; Panagi, Zoi; Avgoustakis, Konstantinos; Reineke, Joshua

2012-01-01

Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity). Clear and systematic understanding of nanoparticle properties’ effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol) (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area) and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to calculate (predict) biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for description of PLGA-mPEG nanoparticle biodistribution. Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to experimental data, reflecting properly developed property–biodistribution relationships. PMID:22419876

Fabrication of functional PLGA-based electrospun scaffolds and their applications in biomedical engineering.

PubMed

Zhao, Wen; Li, Jiaojiao; Jin, Kaixiang; Liu, Wenlong; Qiu, Xuefeng; Li, Chenrui

2016-02-01

Electrospun PLGA-based scaffolds have been applied extensively in biomedical engineering, such as tissue engineering and drug delivery system. Due to lack of the recognition sites on cells, hydropholicity and single-function, the applications of PLGA fibrous scaffolds are limited. In order to tackle these issues, many works have been done to obtain functional PLGA-based scaffolds, including surface modifications, the fabrication of PLGA-based composite scaffolds and drug-loaded scaffolds. The functional PLGA-based scaffolds have significantly improved cell adhesion, attachment and proliferation. Moreover, the current study has summarized the applications of functional PLGA-based scaffolds in wound dressing, vascular and bone tissue engineering area as well as drug delivery system. Copyright © 2015 Elsevier B.V. All rights reserved.

Measurement of creatinine in human plasma using a functional porous polymer structure sensing motif

PubMed Central

Nanda, Sitansu Sekhar; An, Seong Soo A; Yi, Dong Kee

2015-01-01

In this study, a new method for detecting creatinine was developed. This novel sensor comprised of two ionic liquids, poly-lactic-co-glycolic acid (PLGA) and 1-butyl-3-methylimidazolium (BMIM) chloride, in the presence of 2′,7′-dichlorofluorescein diacetate (DCFH-DA). PLGA and BMIM chloride formed a functional porous polymer structure (FPPS)-like structure. Creatinine within the FPPS rapidly hydrolyzed and released OH−, which in turn converted DCFH-DA to DCFH, developing an intense green color or green fluorescence. The conversion of DCFH to DCF+ resulted in swelling of FPPS and increased solubility. This DCF+-based sensor could detect creatinine levels with detection limit of 5 µM and also measure the creatinine in blood. This novel method could be used in diagnostic applications for monitoring individuals with renal dysfunction. PMID:26347475

New PLGA-P188-PLGA matrix enhances TGF-β3 release from pharmacologically active microcarriers and promotes chondrogenesis of mesenchymal stem cells.

PubMed

Morille, Marie; Van-Thanh, Tran; Garric, Xavier; Cayon, Jérôme; Coudane, Jean; Noël, Danièle; Venier-Julienne, Marie-Claire; Montero-Menei, Claudia N

2013-08-28

The use of injectable scaffolding materials for in vivo tissue regeneration has raised great interest in various clinical applications because it allows cell implantation through minimally invasive surgical procedures. In case of cartilage repair, a tissue engineered construct should provide a support for the cell and allow sustained in situ delivery of bioactive factors capable of inducing cell differentiation into chondrocytes. Pharmacologically active microcarriers (PAMs), made of biodegradable poly(d,l-lactide-co-glycolide acid) (PLGA), are a unique system, which combines these properties in an adaptable and simple microdevice. However, a limitation of such scaffold is low and incomplete protein release that occurs using the hydrophobic PLGA based microspheres. To circumvent this problem, we developed a novel formulation of polymeric PAMs containing a P188 poloxamer, which protects the protein from denaturation and may positively affect chondrogenesis. This poloxamer was added as a free additive for protein complexation and as a component of the scaffold covalently linked to PLGA. This procedure allows getting a more hydrophilic scaffold but also retaining the protective polymer inside the microcarriers during their degradation. The novel PLGA-P188-PLGA PAMs presenting a fibronectin-covered surface allowed enhanced MSC survival and proliferation. When engineered with TGFβ3, they allowed the sustained release of 70% of the incorporated TGF-β3 over time. Importantly, they exerted superior chondrogenic differentiation potential compared to previous FN-PAM-PLGA-TGF-β3, as shown by an increased expression of specific cartilage markers such as cartilage type II, aggrecan and COMP. Therefore, this microdevice represents an efficient easy-to-handle and injectable tool for cartilage repair. Copyright © 2013 Elsevier B.V. All rights reserved.

Current Strategies in the Modification of PLGA-based Gene Delivery System.

PubMed

Ramezani, Mohammad; Ebrahimian, Mahboubeh; Hashemi, Maryam

2017-01-01

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 genes efficiently. This formulation has several advantages in comparison with other formulations including improvement in solubility, stability, controlling of degradation and release of the entrapped agents. For application of PLGA as a gene carrier, there exist many challenges. PLGA NPs could protect the encapsulated DNA from in vivo degradation but the DNA release is slow and the 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 cytotoxicity, to enhance delivery efficiency and to target specific tissues/cells. This review summarizes different methods used for the preparation of PLGA NPs as gene carriers and recent strategies for the modification of PLGA particles applied in gene therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Preparation and characterization of monodisperse large-porous silica microspheres as the matrix for protein separation.

PubMed

Xia, Hongjun; Wan, Guangping; Zhao, Junlong; Liu, Jiawei; Bai, Quan

2016-11-04

High performance liquid chromatography (HPLC) is a kind of efficient separation technology and has been used widely in many fields. Micro-sized porous silica microspheres as the most popular matrix have been used for fast separation and analysis in HPLC. In this paper, the monodisperse large-porous silica microspheres with controllable size and structure were successfully synthesized with polymer microspheres as the templates and characterized. First, the poly(glycidyl methacrylate-co-ethyleneglycol dimethacrylate) microspheres (P GMA-EDMA ) were functionalized with tetraethylenepentamine (TEPA) to generate amino groups which act as a catalyst in hydrolysis of tetraethyl orthosilicate (TEOS) to form Si-containing low molecular weight species. Then the low molecular weight species diffused into the functionalized P GMA-EDMA microspheres by induction force of the amino groups to form polymer/silica hybrid microspheres. Finally, the organic polymer templates were removed by calcination, and the large-porous silica microspheres were obtained. The compositions, morphology, size distribution, specific surface area and pore size distribution of the porous silica microspheres were characterized by infrared analyzer, scanning-electron microscopy, dynamic laser scattering, the mercury intrusion method and thermal gravimetric analysis, respectively. The results show that the agglomeration of the hybrid microspheres can be overcome when the templates were functionalized with TEPA as amination reagent, and the yield of 95.7% of the monodisperse large-porous silica microspheres can be achieved with high concentration of polymer templates. The resulting large-porous silica microspheres were modified with octadecyltrichlorosilane (ODS) and the chromatographic evaluation was performed by separating the proteins and the digest of BSA. The baseline separation of seven kinds of protein standards was achieved, and the column delivered a better performance when separating BSA digests

Bone Regeneration from PLGA Micro-Nanoparticles

PubMed Central

Ortega-Oller, Inmaculada; Galindo-Moreno, Pablo; 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

Porous polymer coatings on metal microneedles for enhanced drug delivery

NASA Astrophysics Data System (ADS)

Ullah, Asad; Kim, Chul Min; Kim, Gyu Man

2018-04-01

We present a simple method to coat microneedles (MNs) uniformly with a porous polymer (PLGA) that can deliver drugs at high rates. Stainless steel (SS) MNs of high mechanical strength were coated with a thin porous polymer layer to enhance their delivery rates. Additionally, to improve the interfacial adhesion between the polymer and MNs, the MN surface was modified by plasma treatment followed by dip coating with polyethyleneimine, a polymer with repeating amine units. The average failure load (the minimum force sufficient for detaching the polymer layer from the surface of SS) recorded for the modified surface coating was 25 N, whereas it was 2.2 N for the non-modified surface. Calcein dye was successfully delivered into porcine skin to a depth of 750 µm by the porous polymer-coated MNs, demonstrating that the developed MNs can pierce skin easily without deformation of MNs; additional skin penetration tests confirmed this finding. For visual comparison, rhodamine B dye was delivered using porous-coated and non-coated MNs in gelatin gel which showed that delivery with porous-coated MNs penetrate deeper when compared with non-coated MNs. Finally, lidocaine and rhodamine B dye were delivered in phosphate-buffered saline (PBS) medium by porous polymer-coated and non-coated MNs. For rhodamine B, drug delivery with the porous-coated MNs was five times higher than that with the non-coated MNs, whereas 25 times more lidocaine was delivered by the porous-coated MNs compared with the non-coated MNs.

Aqueous Two Phase System Assisted Self-Assembled PLGA Microparticles

NASA Astrophysics Data System (ADS)

Yeredla, Nitish; Kojima, Taisuke; Yang, Yi; Takayama, Shuichi; Kanapathipillai, Mathumai

2016-06-01

Here, we produce poly(lactide-co-glycolide) (PLGA) based microparticles with varying morphologies, and temperature responsive properties utilizing a Pluronic F127/dextran aqueous two-phase system (ATPS) assisted self-assembly. The PLGA polymer, when emulsified in Pluronic F127/dextran ATPS, forms unique microparticle structures due to ATPS guided-self assembly. Depending on the PLGA concentration, the particles either formed a core-shell or a composite microparticle structure. The microparticles facilitate the simultaneous incorporation of both hydrophobic and hydrophilic molecules, due to their amphiphilic macromolecule composition. Further, due to the lower critical solution temperature (LCST) properties of Pluronic F127, the particles exhibit temperature responsiveness. The ATPS based microparticle formation demonstrated in this study, serves as a novel platform for PLGA/polymer based tunable micro/nano particle and polymersome development. The unique properties may be useful in applications such as theranostics, synthesis of complex structure particles, bioreaction/mineralization at the two-phase interface, and bioseparations.

PLGA nanoparticles improve the oral bioavailability of curcumin in rats: characterizations and mechanisms.

PubMed

Xie, Xiaoxia; Tao, Qing; Zou, Yina; Zhang, Fengyi; Guo, Miao; Wang, Ying; Wang, Hui; Zhou, Qian; Yu, Shuqin

2011-09-14

The overall goal of this paper was to develop poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs) of curcumin (CUR), named CUR-PLGA-NPs, and to study the effect and mechanisms enhancing the oral bioavailability of CUR. CUR-PLGA-NPs were prepared according to a solid-in-oil-in-water (s/o/w) solvent evaporation method and exhibited a smooth and spherical shape with diameters of about 200 nm. Characterization of CUR-PLGA-NPs showed CUR was successfully encapsulated on the PLGA polymer. The entrapment efficiency and loading rate of CUR were 91.96 and 5.75%, respectively. CUR-PLGA-NPs showed about 640-fold in water solubility relative to that of n-CUR. A sustained CUR release to a total of approximately 77% was discovered from CUR-PLGA-NPs in artificial intestinal juice, but only about 48% in artificial gastric juice. After oral administration of CUR-PLGA-NPs, the relative bioavailability was 5.6-fold and had a longer half-life compared with that of native curcumin. The results showed that the effect in improving oral bioavailability of CUR may be associated with improved water solubility, higher release rate in the intestinal juice, enhanced absorption by improved permeability, inhibition of P-glycoprotein (P-gp)-mediated efflux, and increased residence time in the intestinal cavity. Thus, encapsulating hydrophobic drugs on PLGA polymer is a promising method for sustained and controlled drug delivery with improved bioavailability of Biopharmaceutics Classification System (BCS) class IV, such as CUR.

PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses

PubMed Central

Ma, Wenxue; Chen, Mingshui; Kaushal, Sharmeela; McElroy, Michele; Zhang, Yu; Ozkan, Cengiz; Bouvet, Michael; Kruse, Carol; Grotjahn, Douglas; Ichim, Thomas; Minev, Boris

2012-01-01

The peptide vaccine clinical trials encountered limited success because of difficulties associated with stability and delivery, resulting in inefficient antigen presentation and low response rates in patients with cancer. The purpose of this study was to develop a novel delivery approach for tumor antigenic peptides in order to elicit enhanced immune responses using poly(DL-lactide-co-glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA-NPs were made using the double emulsion-solvent evaporation method. Artificial antigen-presenting cells were generated by human dendritic cells (DCs) loaded with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the antigen presentation was measured by interferon-γ ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96® Non-Radioactive Cytotoxicity Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was compared between the methods of emulsification in incomplete Freund’s adjuvant and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a mean zeta potential of −15.53 ± 0.71 mV; the PLGA-NPs could be colocalized in human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs encapsulating peptide induced significantly stronger CTL cytotoxicity than those pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a three-peptide cocktail induced a significantly greater CTL response than those encapsulating a two-peptide cocktail. Most importantly, the peptide dose encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete Freund’s adjuvant, but it induced a more powerful CTL response in vivo. These results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a promising approach to induce effective antitumor

PLGA/Ag nanocomposites: in vitro degradation study and silver ion release.

PubMed

Fortunati, E; Latterini, L; Rinaldi, S; Kenny, J M; Armentano, I

2011-12-01

New nanocomposite films based on a biodegradable poly (DL-Lactide-co-Glycolide) copolymer (PLGA) and different concentration of silver nanoparticles (Ag) were developed by solvent casting. In vitro degradation studies of PLGA/Ag nanocomposites were conducted under physiological conditions, over a 5 week period, and compared to the behaviour of the neat polymer. Furthermore the silver ions (Ag(+)) release upon degradation was monitored to obtain information on the properties of the nanocomposites during the incubation. The obtained results suggest that the PLGA film morphology can be modified introducing a small percentage of silver nanoparticles that do not affect the degradation mechanism of PLGA polymer in the nanocomposite. However results clearly evinced the stabilizing effect of the Ag nanoparticles in the PLGA polymer and the mineralization process induced by the combined effect of silver and nanocomposite surface topography. The Ag(+) release can be controlled by the polymer degradation processes, evidencing a prolonged antibacterial effect.

Large-size porous ZnO flakes with superior gas-sensing performance

NASA Astrophysics Data System (ADS)

Wen, Wei; Wu, Jin-Ming; Wang, Yu-De

2012-06-01

A simple top-down route is developed to fabricate large size porous ZnO flakes via solution combustion synthesis followed by a subsequent calcination in air, which is template-free and can be easily enlarged to an industrial scale. The achieved porous ZnO flakes, which are tens to hundreds of micrometers in flat and tens of nanometers in thickness, exhibit high response for detecting acetone and ethanol, because the unique two-dimensional architecture shortens effectively the gas diffusion distance and provides highly accessible open channels and active surfaces for the target gas.

Current advances in research and clinical applications of PLGA-based nanotechnology

PubMed Central

Lü, Jian-Ming; Wang, Xinwen; Marin-Muller, Christian; Wang, Hao; Lin, Peter H; Yao, Qizhi; Chen, Changyi

2009-01-01

Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been developed for many years and has been approved by the US FDA for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. This article presents the more recent successes of applying PLGA-based nanotechnologies and tools in these medicine-related applications. It focuses on the possible mechanisms, diagnosis and treatment effects of PLGA preparations and devices. This updated information will benefit to both new and established research scientists and clinical physicians who are interested in the development and application of PLGA nanotechnology as new therapeutic and diagnostic strategies for many diseases. PMID:19435455

Antiplasmodial Activity and Toxicological Assessment of Curcumin PLGA-Encapsulated Nanoparticles

PubMed Central

Busari, Zulaikha A.; Dauda, Kabiru A.; Morenikeji, Olajumoke A.; Afolayan, Funmilayo; Oyeyemi, Oyetunde T.; Meena, Jairam; Sahu, Debasis; Panda, Amulya K.

2017-01-01

Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Curcumin was loaded with poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation from oil-in-water single emulsion method. The nanoparticles were characterized and evaluated in vivo for antimalarial activities using Peter’s 4-day suppressive protocol in mice model. Hematological and hepatic toxicity assays were performed on whole blood and plasma, respectively. In vivo anti-parasitic test and toxicity assays for free and encapsulated drug were performed at 5 and 10 mg/kg. In vitro cytotoxicity of free and PLGA encapsulated curcumin (Cur-PLGA) to RAW 264.7 cell line was also determined at varying concentrations (1000–7.8 μg/mL). The size and entrapment efficiency of the nanoparticulate drug formulated was 291.2 ± 82.1 nm and 21.8 ± 0.4 respectively. The percentage parasite suppression (56.8%) at 5 mg/kg was significantly higher than in free drug (40.5%) of similar concentration (p < 0.05) but not at 10 mg/kg (49.5%) at 4-day post-treatment. There were no significant differences in most of the recorded blood parameters in free curcumin and PLGA encapsulated nanoparticulate form (p > 0.05) except in lymphocytes which were significantly higher in Cur-PLGA compared to the free drug (p < 0.05). There were no significant differences in hepatotoxic biomarkers; aspartate aminotransferase and alanine aminotransferase concentrations in various treatment groups (p > 0.05). At higher concentrations (1000 and 500 μg/mL), Cur-PLGA entrapped

Tetraiodothyroacetic acid-conjugated PLGA nanoparticles: a nanomedicine approach to treat drug-resistant breast cancer

PubMed Central

Bharali, Dhruba J; Yalcin, Murat; Davis, Paul J; Mousa, Shaker A

2013-01-01

Aim The aim was to evaluate tetraiodothyroacetic acid (tetrac), a thyroid hormone analog of l-thyroxin, conjugated to poly(lactic-co-glycolic acid) nanoparticles (T-PLGA-NPs) both in vitro and in vivo for the treatment of drug-resistant breast cancer. Materials & methods The uptake of tetrac and T-PLGA-NPs in doxorubicin-resistant MCF7 (MCF7-Dx) cells was evaluated using confocal microscopy. Cell proliferation assays and a chick chorioallantoic membrane model of FGF2-induced angiogenesis were used to evaluate the anticancer effects of T-PLGA-NPs. In vivo efficacy was examined in a MCF7-Dx orthotopic tumor BALBc nude mouse model. Results T-PLGA-NPs were restricted from entering into the cell nucleus, and T-PLGA-NPs inhibited angiogenesis by 100% compared with 60% by free tetrac. T-PLGA-NPs enhanced inhibition of tumor-cell proliferation at a low-dose equivalent of free tetrac. In vivo treatment with either tetrac or T-PLGA-NPs resulted in a three- to five-fold inhibition of tumor weight. Conclusion T-PLGA-NPs have high potential as anticancer agents, with possible applications in the treatment of drug-resistant cancer. PMID:23448245

Poly(d,l)-lactide-co-glycolide (PLGA) microspheres as immunoadjuvant for Brugia malayi antigens.

PubMed

Saini, Vinay; Verma, Shiv Kumar; Murthy, P Kalpana; Kohli, Dharmveer

2013-08-28

Recently we identified in Brugia malayi adult worm extract (BmA) a pro-inflammatory 54-68kDa SDS-PAGE resolved fraction F6 that protects the host from the parasite via Th1/Th2 type responses. We are currently investigating F6 as a potential source of vaccine candidate(s) and the present study is aimed at investigating the suitability of poly(d,l)-lactide-co-glycolide microspheres (PLGA-Ms) as immunoadjuvant for the antigen administration in a single dose. PLGA-Ms were prepared aseptically by a modified double emulsion (w/o/w) solvent evaporation technique and their size, shape, antigen adsorption efficiency, in-process stability, and antigen release were characterized. Swiss mice were immunized by a single subcutaneous administration of BmA and F6 adsorbed on PLGA-Ms (lactide:glycolide ratios 50:50 and 75:25) and the immune responses were compared with administration of 1 or 2 doses of plain BmA and F6. Specific IgG, IgG1, IgG2a, IgG2b, IgE levels in serum, cellular-proliferative response and release of IFN-γ, TNF-α and nitric oxide from the cells of immunized host in response to the antigens/LPS/Con A challenge and antibody-dependant cellular cytotoxicity (ADCC) to parasite life stages were determined. The average size of PLGA-Ms 50:50 was smaller than the size of PLGA-Ms 75:25 and the % antigen adsorption efficiency of PLGA-Ms 50:50 was greater than PLGA-Ms 75:25. Single shot injection of PLGA-Ms 50:50/75:25-BmA/F6 produced better and stronger IgG, IgG1/IgG2a and cell-mediated immune responses than even two injections of plain BmA or F6. Further, PLGA-Ms 50:50-F6 produced stronger responses than PLGA-Ms 50:50-BmA. Anti-PLGA-Ms 50:50-F6 antibodies elicited higher ADCC response to infective larval and microfilarial stages of the parasite than anti-PLGA-Ms 75:25-F6 antibodies. The findings demonstrate that PLGA-Ms 50:50 is an excellent adjuvant for use with F6 in a single administration. This is the first ever report on PLGA as immunoadjuvant for filarial antigens

Low temperature gamma sterilization of a bioresorbable polymer, PLGA

NASA Astrophysics Data System (ADS)

Davison, Lisa; Themistou, Efrosyni; Buchanan, Fraser; Cunningham, Eoin

2018-02-01

Medical devices destined for insertion into the body must be sterilised before implantation to prevent infection or other complications. Emerging biomaterials, for example bioresorbable polymers, can experience changes in their properties due to standard industrial sterilization processes. Gamma irradiation is one of the most reliable, large scale sterilization methods, however it can induce chain scission, cross-linking or oxidation reactions in polymers. sterilization at low temperature or in an inert atmosphere has been reported to reduce the negative effects of gamma irradiation. The aim of this study was to investigate the impact of low temperature sterilization (at -80 °C) when compared to sterilization at ambient temperature (25 °C) both in inert atmospheric conditions of nitrogen gas, on poly(lactide co-glycolide) (PLGA). PLGA was irradiated at -80 and 25 °C at 40 kGy in a nitrogen atmosphere. Samples were characterised using differential scanning calorimetry (DSC), tensile test, Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC). The results showed that the molecular weight was significantly reduced as was the glass transition temperature, an indication of chain scission. FTIR showed small changes in chemical structure in the methyl and carbonyl groups after irradiation. Glass transition temperature was significantly different between irradiation at -80 °C and irradiation at 25 °C, however this was a difference of only 1 °C. Ultimately, the results indicate that the sterilization temperature used does not affect PLGA when carried out in a nitrogen atmosphere.

Trojan particles: Large porous carriers of nanoparticles for drug delivery

PubMed Central

Tsapis, N.; Bennett, D.; Jackson, B.; Weitz, D. A.; Edwards, D. A.

2002-01-01

We have combined the drug release and delivery potential of nanoparticle (NP) systems with the ease of flow, processing, and aerosolization potential of large porous particle (LPP) systems by spray drying solutions of polymeric and nonpolymeric NPs into extremely thin-walled macroscale structures. These hybrid LPPs exhibit much better flow and aerosolization properties than the NPs; yet, unlike the LPPs, which dissolve in physiological conditions to produce molecular constituents, the hybrid LPPs dissolve to produce NPs, with the drug release and delivery advantages associated with NP delivery systems. Formation of the large porous NP (LPNP) aggregates occurs via a spray-drying process that ensures the drying time of the sprayed droplet is sufficiently shorter than the characteristic time for redistribution of NPs by diffusion within the drying droplet, implying a local Peclet number much greater than unity. Additional control over LPNPs physical characteristics is achieved by adding other components to the spray-dried solutions, including sugars, lipids, polymers, and proteins. The ability to produce LPNPs appears to be largely independent of molecular component type as well as the size or chemical nature of the NPs. PMID:12200546

PLGA based drug delivery systems: Promising carriers for wound healing activity.

PubMed

Chereddy, Kiran Kumar; Vandermeulen, Gaëlle; Préat, Véronique

2016-03-01

Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned. © 2016 by the Wound Healing Society.

Phagocytosis of PLGA Microparticles in Rat Peritoneal Exudate Cells: A Time-Dependent Study

NASA Astrophysics Data System (ADS)

Gomes, Anderson De Jesus; Nain Lunardi, Claure; Henrique Caetano, Flávio; Orive Lunardi, Laurelúcia; da Hora Machado, Antonio Eduardo

2006-07-01

With the purpose of enhancing the efficacy of microparticle-encapsulated therapeutic agents, in this study we evaluated the phagocytic ability of rat peritoneal exudate cells and the preferential location of poly(D,L-lactide-co-glycolic acid) (PLGA) microparticles inside these cells. The microparticles used were produced by a solvent evaporation method and were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Size distribution analysis using DLS and SEM showed that the particles were spherical, with diameters falling between 0.5 and 1.5 [mu]m. Results from cell adhesion by SEM assay, indicated that the PLGA microparticles are not toxic to cells and do not cause any distinct damage to them as confirmed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Among the large variety of cell populations found in the peritoneal exudates (neutrophils, eosinophils, monocytes, and macrophages), TEM showed that only the latter phagocytosed PLGA microparticles, in a time-dependent manner. The results obtained indicate that the microparticles studied show merits as possible carriers of drugs for intracellular delivery.

Preparation and Evaluations of Mangiferin-Loaded PLGA Scaffolds for Alveolar Bone Repair Treatment Under the Diabetic Condition.

PubMed

Li, Hao; Liao, Hongbing; Bao, Chongyun; Xiao, Yu; Wang, Qi

2017-02-01

The aim of the present study was to prepare and evaluate a sustained-release mangiferin scaffold for improving alveolar bone defect repair in diabetes. Mangiferin-loaded poly(D,L-lactide-co-glycolide) (PLGA) scaffolds were prepared using a freeze-drying technique with ice particles as the porogen material. The produced scaffolds were examined using a scanning electron microscope (SEM). Drug content and drug release were detected using a spectrophotometer. Degradation behaviors were monitored as a measure of weight loss and examined using SEM. Then, the scaffolds were incubated with rat bone marrow stromal cells under the diabetic condition in vitro, and cell viability was assessed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Afterward, the scaffolds were implanted into alveolar bone defects of diabetic rats, and bone repair was examined using hematoxylin and eosin staining. The fabricated scaffolds showed porous structures, with average pore size range from 111.35 to 169.45 μm. A higher PLGA concentration led to decreased average pore size. A lower PLGA concentration or a higher mangiferin concentration resulted in increased drug content. The prepared scaffolds released mangiferin in a sustained manner with relatively low initial burst during 10 weeks. Their degradation ratios gradually increased as degradation proceeded. The mangiferin-loaded scaffolds attenuated cell viability decrease under the diabetic condition in vitro. Moreover, they increased histological scorings of bone regeneration and improved delayed alveolar bone defect healing in diabetic rats. These results suggest that the produced mangiferin-loaded scaffolds may provide a potential approach in the treatment of impaired alveolar bone healing in diabetes.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel akermanite/poly (lactic-co-glycolic acid) porous composite scaffold fabricated via a solvent casting-particulate leaching method improved by solvent self-proliferating process.

PubMed

Deng, Yao; Zhang, Mengjiao; Chen, Xianchun; Pu, Ximing; Liao, Xiaoming; Huang, Zhongbing; Yin, Guangfu

2017-08-01

Desirable scaffolds for tissue engineering should be biodegradable carriers to supply suitable microenvironments mimicked the extracellular matrices for desired cellular interactions and to provide supports for the formation of new tissues. In this work, a kind of slightly soluble bioactive ceramic akermanite (AKT) powders were aboratively selected and introduced in the PLGA matrix, a novel l-lactide modified AKT/poly (lactic- co -glycolic acid) (m-AKT/PLGA) composite scaffold was fabricated via a solvent casting-particulate leaching method improved by solvent self-proliferating process. The effects of m-AKT contents on properties of composite scaffolds and on MC3T3-E1 cellular behaviors in vitro have been primarily investigated. The fabricated scaffolds exhibited three-dimensional porous networks, in which homogenously distributed cavities in size of 300-400 μm were interconnected by some smaller holes in a size of 100-200 μm. Meanwhile, the mechanical structure of scaffolds was reinforced by the introduction of m-AKT. Moreover, alkaline ionic products released by m-AKT could neutralize the acidic degradation products of PLGA, and the apatite-mineralization ability of scaffolds could be largely improved. More valuably, significant promotions on adhesion, proliferation, and differentiation of MC3T3-E1 have been observed, which implied the calcium, magnesium and especially silidous ions released sustainably from composite scaffolds could regulate the behaviors of osteogenesis-related cells.

PLGA-based drug delivery systems: importance of the type of drug and device geometry.

PubMed

Klose, D; Siepmann, F; Elkharraz, K; Siepmann, J

2008-04-16

Different types of ibuprofen- and lidocaine-loaded, poly(lactic-co-glycolic acid) (PLGA)-based microparticles and thin, free films of various dimensions were prepared and physico-chemically characterized in vitro. The obtained experimental results were analyzed using mathematical theories based on Fick's second law of diffusion. Importantly, the initial drug loadings were low in all cases (4%, w/w), simplifying the mathematical treatment and minimizing potential effects of the acidic/basic nature of the two model drugs on polymer degradation. Interestingly, the type of drug and device geometry strongly affected the resulting release kinetics and relative importance of the involved mass transport mechanisms. For instance, the relative release rate was almost unaffected by the system size in the case of spherical microparticles, but strongly depended on the thickness of thin, free films, irrespective of the type of drug. Ibuprofen and lidocaine release was found to be primarily diffusion controlled from the investigated PLGA-based microparticles for all system sizes, whereas diffusion was only dominant in the case of the thinnest free films. Interestingly, the type of drug did not significantly affect the resulting polymer degradation kinetics. However, ibuprofen release was always much faster than lidocaine release for all system geometries and sizes. This can probably be attributed to attractive ionic interactions between protonated, positively charged lidocaine ions and negatively charged, deprotonated carboxylic end groups of PLGA, hindering drug diffusion. The determined apparent diffusion coefficients of the drugs clearly point out that the mobility of an active agent in PLGA-based delivery systems does not only depend on its own physico-chemical properties and the type of PLGA used, but also to a large extent on the size and shape of the device. This has to be carefully taken into account when developing/optimizing this type of advanced drug delivery systems.

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. Copyright © 2014 Elsevier B.V. All rights reserved.

PLGA-Mesoporous Silicon Microspheres for the in Vivo Controlled Temporospatial Delivery of Proteins.

PubMed

Minardi, Silvia; Pandolfi, Laura; Taraballi, Francesca; De Rosa, Enrica; Yazdi, Iman K; Liu, Xeuwu; Ferrari, Mauro; Tasciotti, Ennio

2015-08-05

In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo. Hence, we proposed a newly developed multiscale composite microsphere based on a core consisting of the nanostructured silicon multistage vector (MSV) and a poly(dl-lactide-co-glycolide) acid (PLGA) outer shell. Both of the two components of the resulting composite microspheres (PLGA-MSV) can be independently tailored to achieve multiple release kinetics contributing to the control of the release profile of a reporter protein in vitro. The influence of MSV shape (hemispherical or discoidal) and size (1, 3, or 7 μm) on PLGA-MSV's morphology and size distribution was investigated. Second, the copolymer ratio of the PLGA used to fabricate the outer shell of PLGA-MSV was varied. The composites were fully characterized by optical microscopy, scanning electron microscopy, ζ potential, Fourier transform infrared spectroscopy, and thermogravimetric analysis-differential scanning calorimetry, and their release kinetics over 30 days. PLGA-MSV's biocompatibility was assessed in vitro with J774 macrophages. Finally, the formulation of PLGA-MSV was selected, which concurrently provided the most consistent microsphere size and allowed for a zero-order release kinetic. The selected PLGA-MSVs were injected in a subcutaneous model in mice, and the in vivo release of the reporter protein was followed over 2 weeks by intravital microscopy, to assess if the zero-order release was preserved. PLGA-MSV was able to retain the payload over 2 weeks, avoiding the initial burst release typical of most drug delivery systems. Finally, histological evaluation assessed the

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.

Magnetic poly(lactide-co-glycolide) (PLGA) and cellulose particles for MRI-based cell tracking

PubMed Central

Nkansah, Michael K.; Thakral, Durga; Shapiro, Erik M.

2010-01-01

Biodegradable, superparamagnetic micro- and nanoparticles of poly(lactide-co-glycolide) (PLGA) and cellulose were designed, fabricated and characterized for magnetic cell labeling. Monodisperse nanocrystals of magnetite were incorporated into micro- and nanoparticles of PLGA and cellulose with high efficiency using an oil-in-water single emulsion technique. Superparamagnetic cores had high magnetization (72.1 emu/g). The resulting polymeric particles had smooth surface morphology and high magnetite content (43.3 wt% for PLGA and 69.6 wt% for cellulose). While PLGA and cellulose nanoparticles displayed highest r2* values per millimole of iron (399 s-1mM-1 for cellulose and 505 s-1mM-1 for PLGA), micron-sized PLGA particles had a much higher r2* per particle than either. After incubation for a month in citrate buffer (pH 5.5), magnetic PLGA particles lost close to 50% of their initial r2* molar relaxivity, while magnetic cellulose particles remained intact, preserving over 85% of their initial r2* molar relaxivity. Lastly, mesenchymal stem cells and human breast adenocarcinoma cells were magnetically labeled using these particles with no detectable cytotoxicity. These particles are ideally suited for non-invasive cell tracking in vivo via MRI and due to their vastly different degradation properties, offer unique potential for dedicated use for either short (PLGA-based particles) or long term (cellulose-based particles) experiments. PMID:21404328

Ozone Gas as a Benign Sterilization Treatment for PLGA Nanofiber Scaffolds

PubMed Central

de Jesus Andreoli Pinto, Terezinha; Bou-Chacra, Nadia Araci; Galante, Raquel; de Araújo, Gabriel Lima Barros; do Nascimento Pedrosa, Tatiana; Maria-Engler, Silvya Stuchi

2016-01-01

The use of electrospun nanofibers for tissue engineering and regenerative medicine applications is a growing trend as they provide improved support for cell proliferation and survival due, in part, to their morphology mimicking that of the extracellular matrix. Sterilization is a critical step in the fabrication process of implantable biomaterial scaffolds for clinical use, but many of the existing methods used to date can negatively affect scaffold properties and performance. Poly(lactic-co-glycolic acid) (PLGA) has been widely used as a biodegradable polymer for 3D scaffolds and can be significantly affected by current sterilization techniques. The aim of this study was to investigate pulsed ozone gas as an alternative method for sterilizing PLGA nanofibers. The morphology, mechanical properties, physicochemical properties, and response of cells to PLGA nanofiber scaffolds were assessed following different degrees of ozone gas sterilization. This treatment killed Geobacillus stearothermophilus spores, the most common biological indicator used for validation of sterilization processes. In addition, the method preserved all of the characteristics of nonsterilized PLGA nanofibers at all degrees of sterilization tested. These findings suggest that ozone gas can be applied as an alternative method for sterilizing electrospun PLGA nanofiber scaffolds without detrimental effects. PMID:26757850

Ozone Gas as a Benign Sterilization Treatment for PLGA Nanofiber Scaffolds.

PubMed

Rediguieri, Carolina Fracalossi; Pinto, Terezinha de Jesus Andreoli; Bou-Chacra, Nadia Araci; Galante, Raquel; de Araújo, Gabriel Lima Barros; Pedrosa, Tatiana do Nascimento; Maria-Engler, Silvya Stuchi; De Bank, Paul A

2016-04-01

The use of electrospun nanofibers for tissue engineering and regenerative medicine applications is a growing trend as they provide improved support for cell proliferation and survival due, in part, to their morphology mimicking that of the extracellular matrix. Sterilization is a critical step in the fabrication process of implantable biomaterial scaffolds for clinical use, but many of the existing methods used to date can negatively affect scaffold properties and performance. Poly(lactic-co-glycolic acid) (PLGA) has been widely used as a biodegradable polymer for 3D scaffolds and can be significantly affected by current sterilization techniques. The aim of this study was to investigate pulsed ozone gas as an alternative method for sterilizing PLGA nanofibers. The morphology, mechanical properties, physicochemical properties, and response of cells to PLGA nanofiber scaffolds were assessed following different degrees of ozone gas sterilization. This treatment killed Geobacillus stearothermophilus spores, the most common biological indicator used for validation of sterilization processes. In addition, the method preserved all of the characteristics of nonsterilized PLGA nanofibers at all degrees of sterilization tested. These findings suggest that ozone gas can be applied as an alternative method for sterilizing electrospun PLGA nanofiber scaffolds without detrimental effects.

Immunization against leishmaniasis by PLGA nanospheres loaded with an experimental autoclaved Leishmania major (ALM) and Quillaja saponins.

PubMed

Tafaghodi, M; Eskandari, M; Kharazizadeh, M; Khamesipour, A; Jaafari, M R

2010-12-01

Immune responses against the Leishmania antigens are not sufficient to protect against a leishmania challenge. Therefore these antigens need to be potentiated by various adjuvants and delivery systems. In this study, Poly (d,l-lactide-co-glycolide (PLGA) nanospheres as antigen delivery system and Quillaja saponins (QS) as immunoadjuvant have been used to enhance the immune response against autoclaved Leishmania major (ALM). PLGA nanospheres were prepared by a double-emulsion (W/O/W) technique. Particulate characteristics were studied by scanning electron microscopy and particle size analysis. Mean diameter for nanospheres loaded with ALM+QS was 294 ± 106 nm. BALB/c mice were immunized three times in 3-weeks intervals using ALM plus QS loaded nanospheres [(ALM+QS)PLGA], ALM encapsulated with PLGA nanospheres [(ALM)PLGA], (ALM)PLGA + QS, ALM + QS, ALM alone or PBS. The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection, showed by significantly (P < 0.05) smaller footpad, were observed in mice immunized with (ALM)PLGA. The (ALM+QS)PLGA group showed the least protection and highest swelling, while the (ALM)PLGA+QS, ALM+QS and ALM showed an intermediate protection with no significant difference. The mice immunized with ALM and ALM+QS showed the highest IgG2a/IgG1 ratio (P < 0.01), followed by (ALM)PLGA+QS. The highest IFN-γ and lowest IL-4 production was seen in (ALM)PLGA+QS, ALM+QS groups. The highest parasite burden was observed in (ALM)PLGA+QS and (ALM+QS)PLGA groups. It is concluded that PLGA nanospheres as a vaccine delivery system could increase the protective immune responses, but QS adjuvant has a reverse effect on protective immune responses and the least protective responses were seen in the presence of this adjuvant.

PLGA/polymeric liposome for targeted drug and gene co-delivery.

PubMed

Wang, Hanjie; Zhao, Peiqi; Su, Wenya; Wang, Sheng; Liao, Zhenyu; Niu, Ruifang; Chang, Jin

2010-11-01

Chemotherapy is one of the most effective approaches to treat cancers in the clinic, but the problems, such as multidrug resistance (MDR), low bioavailability and toxicity, severely constrain the further application of chemotherapy. Our group recently reported that cationic PLGA/folate coated PEGlated polymeric liposome core-shell nanoparticles (PLGA/FPL NPs). It was self-assembled from a hydrophobic PLGA core and a hydrophilic folate coated PEGlated lipid shell for targeting co-delivery of drug and gene. Hydrophobic drugs can be incorporated into the core and the cationic shell of the drug-loaded nanoparticles can be used to bind DNA. The drug-loaded PLGA/FPL NPs/DNA complexes offer advantages to overcome these problems mentioned above, such as co-delivery of drugs and DNA to improving the chemosensitivity of cancer cells at a gene level, and targeting delivery of drug to the cancer tissue that enhance the bioavailability and reduce the toxicity. The experiment showed that nanoparticles have core-shell structure with nanosize, sustained drug release profile and good DNA-binding ability. Importantly, the core-shell nanoparticles achieve the possibility of co-delivering drugs and genes to the same cells with high gene transfection and drug delivery efficiency. Our data suggest that the PLGA/FPL NPs may be a useful drug and gene co-delivery system. Copyright © 2010 Elsevier Ltd. All rights reserved.

Tailoring sub-micron PLGA particle release profiles via centrifugal fractioning

PubMed Central

Dutta, Dipankar; Salifu, Mariama; Sirianni, Rachael W.; Stabenfeldt, Sarah E.

2016-01-01

Poly(D,L-lactic-co-glycolic) acid (PLGA)-based submicron particles are uniquely posed to overcome limitations of conventional drug delivery systems. However, tailoring cargo/payload release profiles from PLGA micro/nanoparticles typically requires optimization of the multi-parameter formulation, where small changes may cause drastic shifts in the resulting release profiles. In this study, we aimed to establish whether refining the average diameter of submicron particle populations after formulation alters protein release profiles. PLGA particles were first produced via double emulsion-solvent evaporation method to encapsulate bovine serum albumin. Particles were then subjected to centrifugal fractioning protocols varying in both spin time and force to determine encapsulation efficiency and release profile of differently sized populations that originated from a single batch. We found the average particle diameter was related to marked alterations in encapsulation efficiencies (range: 36.4–49.4%), burst release (range: 15.8–49.1%), and time for total cargo release (range: 38–78 days). Our data corroborate previous reports relating PLGA particle size with such release characteristics, however, this is the first study, to our knowledge, to directly compare particle population size while holding all formulation parameters constant. In summary, centrifugal fractioning to selectively control the population distribution of sub-micron PLGA particles represents a feasible tool to tailor release characteristics. PMID:26517011

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

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.

Immunization against leishmaniasis by PLGA nanospheres encapsulated with autoclaved Leishmania major (ALM) and CpG-ODN.

PubMed

Tafaghodi, Mohsen; Khamesipour, Ali; Jaafari, Mahmoud R

2011-05-01

Various adjuvants and delivery systems have been evaluated for increasing the protective immune responses against leishmaniasis and mostly have been shown not to be effective enough. In this study, poly(D,L-lactide-co-glycolide) (PLGA) nanospheres as an antigen delivery system and CpG-ODN as an immunoadjuvant have been used for the first time to enhance the immune response against autoclaved Leishmania major (ALM). PLGA nanospheres were prepared by a double-emulsion (W/O/W) technique. Particulate characteristics were studied by scanning electron microscopy and particle size analysis. Mean diameter of ALM + CpG-ODN-loaded nanospheres was 300 ± 128 nm. BALB/c mice were immunized three times in 3-week intervals using ALM plus CpG-ODN-loaded nanospheres [(ALM + CpG-ODN)(PLGA)], ALM encapsulated PLGA nanospheres [(ALM)(PLGA)], (ALM)(PLGA) + CpG, ALM + CpG, ALM alone, or phosphate buffer solution (PBS). The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection, showed by significantly (P<0.05) smaller footpad, was observed in mice immunized with (ALM + CpG-ODN)(PLGA). The (ALM)(PLGA), (ALM)(PLGA) + CpG, and ALM + CpG were also showed a significantly (P<0.05) smaller footpad swelling compared to the groups received either PBS or ALM alone. The mice immunized with (ALM + CpG-ODN)(PLGA), (ALM)(PLGA) + CpG, and ALM + CpG showed the highest IgG2a/IgG1 ratio, interferon-γ production, and lowest interleukin-4 production compared to the other groups. It is concluded that when both PLGA nanospheres and CpG-ODN adjuvants were used simultaneously, it induce stronger immune response and enhance protection rate against Leishmania infection.

Preparation, characterization and immunological evaluation: canine parvovirus synthetic peptide loaded PLGA nanoparticles.

PubMed

Derman, Serap; Mustafaeva, Zeynep Akdeste; Abamor, Emrah Sefik; Bagirova, Melahat; Allahverdiyev, Adil

2015-10-20

Canine parvovirus 2 (CPV-2) remains a significant worldwide canine pathogen and the most common cause of viral enteritis in dogs. The 1 L15 and 7 L15 peptides overlap each other with QPDGGQPAV residues (7-15 of VP2 capsid protein of CPV) is shown to produce high immune response. PLGA nanoparticles were demonstrated to have special properties such as; controlled antigen release, protection from degradation, elimination of booster-dose and enhancing the cellular uptake by antigen presenting cells. Nevertheless, there is no study available in literature, about developing vaccine based on PLGA nanoparticles with adjuvant properties against CPV. Thus, the aim of the present study was to synthesize and characterize high immunogenic W-1 L19 peptide (from the VP2 capsid protein of CPV) loaded PLGA nanoparticle and to evaluate their in vitro immunogenic activity. PLGA nanoparticles were produced with 5.26 ± 0.05 % loading capacity and high encapsulation efficiency with 81.2 ± 3.1 %. Additionally, it was evaluated that free NPs and W-1 L19 peptide encapsulated PLGA nanoparticles have Z-ave of 183.9 ± 12.1 nm, 221.7 ± 15.8 nm and polydispersity index of 0.107 ± 0.08, 0.135 ± 0.12 respectively. It was determined that peptide loaded PLGA nanoparticles were successfully phagocytized by macrophage cells and increased NO production at 2-folds (*P < 0.05) in contrast to free peptide, and 3-folds (*P < 0.01) in contrast to control. In conclusion, for the first time, W-1 L19 peptide loaded PLGA nanoparticles were successfully synthesized and immunogenic properties evaluated. Obtained results showed that PLGA nanoparticles enhanced the capacity of W-1 L19 peptide to induce nitric oxide production in vitro due to its adjuvant properties. Depend on the obtained results, these nanoparticles can be accepted as potential vaccine candidate against Canine Parvovirus. Studies targeting PLGA nanoparticles based delivery system must be maintained in near

PLGA Nanoparticles and Their Versatile Role in Anticancer Drug Delivery.

PubMed

Khan, Iliyas; Gothwal, Avinash; Sharma, Ashok Kumar; Kesharwani, Prashant; Gupta, Lokesh; Iyer, Arun K; Gupta, Umesh

2016-01-01

Nanotechnological advancement has become a key standard for the diagnosis and treatment of several complex disorders such as cancer by utilizing the enhanced permeability and retention effect and tumor-specific targeting. Synthesis and designing the formulation of active agents in terms of their efficient delivery is of prime importance for healthcare. The use of nanocarriers has resolved the undesirable characteristics of anticancer drugs such as low solubility and poor permeability in cells. Several types of nanoparticles (NPs) have been designed with the use of various polymers along or devoid of surface engineering for targeting tumor cells. All NPs include polymers in their framework and, of these, polylactide-co-glycolide (PLGA) is biodegradable and Food and Drug Administration approved for human use. PLGA has been used extensively in the development of NPs for anticancer drug delivery. The extensive use of PLGA NPs is promising for cancer therapy, with higher efficiency and less adverse effects. The present review focused on recent developments regarding PLGA NPs, the methods used for their preparation, their characterization, and their utility in the delivery of chemotherapeutic agents.

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.

[Preparation of ASODN-protamine-HSA-PLGA nanoparticles and initial evaluation of their nucleus targeting property in vitro].

PubMed

Zhang, Yi; Yuan, Li; Yan, Xiao-ling; Gong, Tao; Liu, Jie; Zhang, Zhi-rong; Sun, Xun

2009-05-01

To develop a novel non-viral gene delivery system-SODN-Protamine-HSA-PLGA (ASODN-P/H-PLGA-NP) and investigate its nucleus targeting potential in vitro. ASODN-P/H-PLGA-NP was prepared by mixing the protamine sulfate and HSA. Then the PLGA nanoparticles were prepared using double-emulsion evaporation technique, followed by addition of ASODN to the prepared P/H complex. The morphology of ASODN-P/H-PLGA-NP was observed by transmission electron microscopy. The diameter, PDI, and surface charge of ASODN-P/H-PLGA-NP were measured by photo correlation spectroscopy (PCS). The encapsulation efficiency of ASODN was determined by double step method. The cytotoxicity of ASODN-P/H-PLGA-NP was investigated by MTT assays. The ability to enter the squamouse carcinoma: Hep-2 cell line and its nucleus targeting property were observed by confocal laser scanning microscope. The average diameter, PDI, zeta potential, and encapsulation efficiency of ASODN-P/H-PLGA-NP were 128 nm, 0.234, -23.3 mV, and 78.45%, respectively. ASODN-P/H-PLGA-NP could protect the ASODN from the shear force in the ultrasound process during preparation. ASODN-P/H-PLGA-NP couldenter Hep-2 cells and have certain level of nucleus targeting property. ASODN-P/H-PLGA-NP can be prepared easily with small particle sizes and low cytotoxicity, which might be employed as a good non-viral vector for applications in ASODN delivery to nucleus.

Combined effects of Ag nanoparticles and oxygen plasma treatment on PLGA morphological, chemical, and antibacterial properties.

PubMed

Fortunati, Elena; Mattioli, Samantha; Visai, Livia; Imbriani, Marcello; Fierro, Josè Luis G; Kenny, Josè Maria; Armentano, Ilaria

2013-03-11

The purpose of this study is to investigate the combined effects of oxygen plasma treatments and silver nanoparticles (Ag) on PLGA in order to modulate the surface antimicrobial properties through tunable bacteria adhesion mechanisms. PLGA nanocomposite films, produced by solvent casting with 1 wt % and 7 wt % of Ag nanoparticles were investigated. The PLGA and PLGA/Ag nanocomposite surfaces were treated with oxygen plasma. Surface properties of PLGA were investigated by field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM), static contact angle (CA), and high resolution X-ray photoelectron spectroscopy (XPS). Antibacterial tests were performed using an Escherichia coli RB (a Gram negative) and Staphylococcus aureus 8325-4 (a Gram positive). The PLGA surface becomes hydrophilic after the oxygen treatment and its roughness increases with the treatment time. The surface treatment and the Ag nanoparticle introduction have a dominant influence on the bacteria adhesion and growth. Oxygen-treated PLGA/Ag systems promote higher reduction of the bacteria viability in comparison to the untreated samples and neat PLGA. The combination of Ag nanoparticles with the oxygen plasma treatment opens new perspectives for the studied biodegradable systems in biomedical applications.

Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation.

PubMed

Hu, Sanyuan; Zhang, Yangde

2010-11-24

Endostar, a novel recombinant human endostatin, which was approved by the Chinese State Food and Drug Administration in 2005, has a broad spectrum of activity against solid tumors. In this study, we aimed to determine whether the anticancer effect of Endostar is increased by using a nanocarrier system. It is expected that the prolonged circulation of endostar will improve its anticancer activity. Endostar-loaded nanoparticles were prepared to improve controlled release of the drug in mice and rabbits, as well as its anticancer effects in mice with colon cancer. A protein release system could be exploited to act as a drug carrier. Nanoparticles were formulated from poly (ethylene glycol) modified poly (DL-lactide-co-glycolide) (PEG-PLGA) by a double emulsion technique. Physical and release characteristics of endostar-loaded nanoparticles in vitro were evaluated by transmission electron microscopy (TEM), photon correlation spectroscopy (PCS), and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked immunosorbent assay. Western blot was used to detect endostatin in different tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice in which tumor cells HT-29 were implanted, were subsequently treated with endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar-loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure with a diameter of 169.56 ± 35.03 nm. Drug-loading capacity was 8.22% ± 2.35% and drug encapsulation was 80.17% ± 7.83%. Compared with endostar, endostar-loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak concentration, caused slower growth of tumor cell xenografts, and prolonged tumor doubling times. The nanoparticles changed the pharmacokinetic characteristics of endostar in mice and rabbits, thereby reinforcing anticancer activity. In conclusion, PEG-PLGA

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

PubMed Central

Nair K, Lekha; Jagadeeshan, Sankar; Nair, S Asha; Kumar, GS Vinod

2011-01-01

Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as controlled release

Nanoparticles in Porous Microparticles Prepared by Supercritical Infusion and Pressure Quench Technology for Sustained Delivery of Bevacizumab

PubMed Central

K.Yandrapu, Sarath; Upadhyay, Arun K.; Petrash, J. Mark; Kompella, Uday B.

2014-01-01

Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for sustained delivery of protein drugs, was developed using supercritical infusion and pressure quench technology, which does not expose proteins to organic solvents or sonication. The delivery system design is based on the ability of supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to bevacizumab, a protein drug administered once a month intravitreally to treat wet age related macular degeneration. Bevacizumab coated PLA nanoparticles were encapsulated into porosifying PLGA microparticles by exposing the mixture to SC CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9 fold. Confocal and scanning electron microscopy studies demonstrated the expansion and porosification of PLGA microparticles and infusion of PLA nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies indicated that the released bevacizumab maintained its monomeric form, conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP was evaluated using noninvasive fluorophotometry after intravitreal administration of Alexa Flour 488 conjugated bevacizumab in either solution or NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases. PMID:24131101

Nanoparticles in porous microparticles prepared by supercritical infusion and pressure quench technology for sustained delivery of bevacizumab.

PubMed

Yandrapu, Sarath K; Upadhyay, Arun K; Petrash, J Mark; Kompella, Uday B

2013-12-02

Nanoparticles in porous microparticles (NPinPMP), a novel delivery system for sustained delivery of protein drugs, was developed using supercritical infusion and pressure quench technology, which does not expose proteins to organic solvents or sonication. The delivery system design is based on the ability of supercritical carbon dioxide (SC CO2) to expand poly(lactic-co-glycolic) acid (PLGA) matrix but not polylactic acid (PLA) matrix. The technology was applied to bevacizumab, a protein drug administered once a month intravitreally to treat wet age related macular degeneration. Bevacizumab coated PLA nanoparticles were encapsulated into porosifying PLGA microparticles by exposing the mixture to SC CO2. After SC CO2 exposure, the size of PLGA microparticles increased by 6.9-fold. Confocal and scanning electron microscopy studies demonstrated the expansion and porosification of PLGA microparticles and infusion of PLA nanoparticles inside PLGA microparticles. In vitro release of bevacizumab from NPinPMP was sustained for 4 months. Size exclusion chromatography, fluorescence spectroscopy, circular dichroism spectroscopy, SDS-PAGE, and ELISA studies indicated that the released bevacizumab maintained its monomeric form, conformation, and activity. Further, in vivo delivery of bevacizumab from NPinPMP was evaluated using noninvasive fluorophotometry after intravitreal administration of Alexa Fluor 488 conjugated bevacizumab in either solution or NPinPMP in a rat model. Unlike the vitreal signal from Alexa-bevacizumab solution, which reached baseline at 2 weeks, release of Alexa-bevacizumab from NPinPMP could be detected for 2 months. Thus, NPinPMP is a novel sustained release system for protein drugs to reduce frequency of protein injections in the therapy of back of the eye diseases.

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

PubMed

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

2012-06-14

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.

Prolonged analgesic effect of PLGA-encapsulated bee venom on formalin-induced pain in rats.

PubMed

Jeong, Injae; Kim, Beom-Soo; Lee, Hyejung; Lee, Kang-Min; Shim, Insop; Kang, Sung-Keel; Yin, Chang-Shick; Hahm, Dae-Hyun

2009-10-01

To enhance the medicinal activity of bee venom (BV) acupuncture, bee venom was loaded into biodegradable poly(D,L-lactide-co-glycolide) nanoparticles (BV-PLGA-NPs) by a water-in-oil-in-water-emulsion/solvent-evaporation technique. Rat formalin tests were performed after subcutaneous injection of BV-PLGA-NPs to the Zusanli acupuncture point (ST36) at 0.5, 1, 2, 6, 12, 24, and 48 h before plantar injection of 2% formalin. BV-PLGA-NPs treatment showed comparable analgesic activity to typical BV acupuncture during the late phase, compared with saline-treated controls, and the analgesic effect lasted for 12h. PLGA-encapsulation was also effective in alleviating the edema induced by allergens in bee venom. These results indicate that PLGA-encapsulation provided a more prolonged effect of BV acupuncture treatment, while maintaining a comparable therapeutic effect.

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.

A novel akermanite/poly (lactic-co-glycolic acid) porous composite scaffold fabricated via a solvent casting-particulate leaching method improved by solvent self-proliferating process

PubMed Central

Deng, Yao; Zhang, Mengjiao; Chen, Xianchun; Pu, Ximing; Liao, Xiaoming; Huang, Zhongbing

2017-01-01

Abstract Desirable scaffolds for tissue engineering should be biodegradable carriers to supply suitable microenvironments mimicked the extracellular matrices for desired cellular interactions and to provide supports for the formation of new tissues. In this work, a kind of slightly soluble bioactive ceramic akermanite (AKT) powders were aboratively selected and introduced in the PLGA matrix, a novel l-lactide modified AKT/poly (lactic-co-glycolic acid) (m-AKT/PLGA) composite scaffold was fabricated via a solvent casting-particulate leaching method improved by solvent self-proliferating process. The effects of m-AKT contents on properties of composite scaffolds and on MC3T3-E1 cellular behaviors in vitro have been primarily investigated. The fabricated scaffolds exhibited three-dimensional porous networks, in which homogenously distributed cavities in size of 300–400 μm were interconnected by some smaller holes in a size of 100–200 μm. Meanwhile, the mechanical structure of scaffolds was reinforced by the introduction of m-AKT. Moreover, alkaline ionic products released by m-AKT could neutralize the acidic degradation products of PLGA, and the apatite-mineralization ability of scaffolds could be largely improved. More valuably, significant promotions on adhesion, proliferation, and differentiation of MC3T3-E1 have been observed, which implied the calcium, magnesium and especially silidous ions released sustainably from composite scaffolds could regulate the behaviors of osteogenesis-related cells. PMID:28798869

Doxorubicin-loaded micelles based on multiarm star-shaped PLGA-PEG block copolymers: influence of arm numbers on drug delivery.

PubMed

Ma, Guilei; Zhang, Chao; Zhang, Linhua; Sun, Hongfan; Song, Cunxian; Wang, Chun; Kong, Deling

2016-01-01

Star-shaped block copolymers based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol) (PEG) (st-PLGA-PEG) were synthesized with structural variation on arm numbers in order to investigate the relationship between the arm numbers of st-PLGA-PEG copolymers and their micelle properties. st-PLGA-PEG copolymers with arm numbers 3, 4 and 6 were synthesized by using different cores such as trimethylolpropane, pentaerythritol and dipentaerythritol, and were characterized by nuclear magnetic resonance and gel permeation chromatography. The critical micelle concentration decreased with increasing arm numbers in st-PLGA-PEG copolymers. The doxorubicin-loaded st-PLGA-PEG micelles were prepared by a modified nanoprecipitation method. Micellar properties such as particle size, drug loading content and in vitro drug release behavior were investigated as a function of the number of arms and compared with each other. The doxorubicin-loaded 4-arm PLGA-PEG micelles were found to have the highest cellular uptake efficiency and cytotoxicity compared with 3-arm PLGA-PEG micelles and 6-arm PLGA-PEG micelles. The results suggest that structural tailoring of arm numbers from st-PLGA-PEG copolymers could provide a new strategy for designing drug carriers of high efficiency. Structural tailoring of arm numbers from star shaped-PLGA-PEG copolymers (3-arm/4-arm/6-arm-PLGA-PEG) could provide a new strategy for designing drug carriers of high efficiency.

Efficient Production of Retroviruses Using PLGA/bPEI-DNA Nanoparticles and Application for Reprogramming Somatic Cells

PubMed Central

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. PMID:24098810

Development of Poly Lactic/Glycolic Acid (PLGA) Microspheres for Controlled Release of Rho-Associated Kinase Inhibitor.

PubMed

Koda, Sho; Okumura, Naoki; Kitano, Junji; Koizumi, Noriko; Tabata, Yasuhiko

2017-01-01

The purpose of this study was to investigate the feasibility of poly lactic/glycolic acid (PLGA) as a drug delivery carrier of Rho kinase (ROCK) inhibitor for the treatment of corneal endothelial disease. ROCK inhibitor Y-27632 and PLGA were dissolved in water with or without gelatin (W1), and a double emulsion [(W1/O)/W2] was formed with dichloromethane (O) and polyvinyl alcohol (W2). Drug release curve was obtained by evaluating the released Y-27632 by using high performance liquid chromatography. PLGA was injected into the anterior chamber or subconjunctiva in rabbit eyes, and ocular complication was evaluated by slitlamp microscope and histological analysis. Y-27632 incorporated PLGA microspheres with different molecular weights, and different composition ratios of lactic acid and glycolic acid were fabricated. A high molecular weight and low content of glycolic acid produced a slower and longer release. The Y-27632 released from PLGA microspheres significantly promoted the cell proliferation of cultured corneal endothelial cells. The injection of PLGA did not induce any evident eye complication. ROCK inhibitor-incorporated PLGA microspheres were fabricated, and the microspheres achieved the sustained release of ROCK inhibitor over 7-10 days in vitro. Our data should encourage researchers to use PLGA microspheres for treating corneal endothelial diseases.

Effect of PLGA as a polymeric emulsifier on preparation of hydrophilic protein-loaded solid lipid nanoparticles.

PubMed

Xie, ShuYu; Wang, SiLiang; Zhao, BaoKai; Han, Chao; Wang, Ming; Zhou, WenZhong

2008-12-01

Most proteins are hydrophilic and poorly encapsulated into the hydrophobic matrix of solid lipid nanoparticles (SLN). To solve this problem, poly (lactic-co-glycolic acid) (PLGA) was utilized as a lipophilic polymeric emulsifier to prepare hydrophilic protein-loaded SLN by w/o/w double emulsion and solvent evaporation techniques. Hydrogenated castor oil (HCO) was used as a lipid matrix and bovine serum albumin (BSA), lysozyme and insulin were used as model proteins to investigate the effect of PLGA on the formulation of the SLN. The results showed that PLGA was essential for the primary w/o emulsification. In addition, the stability of the w/o emulsion, the encapsulation efficiency and loading capacity of the nanoparticles were enhanced with the increase of PLGA concentration. Furthermore, increasing PLGA concentration decreased zeta potential significantly but had no influence on particle size of the SLN. In vitro release study showed that PLGA significantly affected the initial burst release, i.e. the higher the content of PLGA, the lower the burst release. The released proteins maintained their integrity and bioactivity as confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and biological assay. These results demonstrated that PLGA was an effective emulsifier for the preparation of hydrophilic protein-loaded SLN.

PLGA nanoparticles codeliver paclitaxel and Stat3 siRNA to overcome cellular resistance in lung cancer cells

PubMed Central

Su, Wen-Pin; Cheng, Fong-Yu; Shieh, Dar-Bin; Yeh, Chen-Sheng; Su, Wu-Chou

2012-01-01

Background: Effective cancer chemotherapy remains an important issue in cancer treatment, and signal transducer and activator of transcription-3 (Stat3) activation leads to cellular resistance of anticancer agents. Polymers are ideal vectors to carry both chemotherapeutics and small interfering ribonucleic acid (siRNA) to enhance antitumor efficacy. In this paper, poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with paclitaxel and Stat3 siRNA were successfully synthesized, and their applications in cancer cells were investigated. Methods: Firstly, paclitaxel was enclosed by PLGA nanoparticles through solvent evaporation. They were then coated with cationic polyethylenimine polymer (PLGA-PEI-TAX), enabling it to carry Stat3 siRNA on its surface through electrostatic interactions (PLGA-PEI-TAX-S3SI). The size, zeta potential, deliver efficacy, and release profile of the PLGA nanocomplexes were characterized in vitro. The cellular uptake, intracellular nanoparticle trajectory, and subsequent cellular events were evaluated after treatment with various PLGA nanocomplexes in human lung cancer A549 cells and A549-derived paclitaxel-resistant A549/T12 cell lines with α-tubulin mutation. Results: A549 and A549/T12 cells contain constitutively activated Stat3, and silencing Stat3 by siRNA made both cancer cells more sensitive to paclitaxel. Therefore, PLGA-PEI-TAX-S3SI was synthesized to test its therapeutic role in A549 and A549/T12 cells. Transmission electron microscopy showed the size of PLGA-PEI-TAX-S3SI to be around 250 nm. PLGA-PEI nanoparticles were nontoxic. PLGA-PEI-TAX was taken up by A549 and A549/T12 cells more than free paclitaxel, and they induced more condensed microtubule bundles and had higher cytotoxicity in these cancer cells. Moreover, the yellowish fluorescence observed in the cytoplasm of the cancer cells indicates that the PLGA-PEI nanoparticles were still simultaneously delivering Oregon Green paclitaxel and cyanine-5-labeled Stat3 siRNA 3

In vitro hemocompatibility and cytocompatibility of dexamethasone-eluting PLGA stent coatings

NASA Astrophysics Data System (ADS)

Zhang, Jiang; Liu, Yang; Luo, Rifang; Chen, Si; Li, Xin; Yuan, Shuheng; Wang, Jin; Huang, Nan

2015-02-01

Drug-eluting stents (DESs) have been an important breakthrough for interventional cardiology applications since 2002. Though successful in reducing restenosis, some adverse clinical problems still emerged, which were mostly caused by the bare-metal stents and non-biodegradable polymer coatings, associated with the delayed endothelialization process. In this study, dexamethasone-loaded poly (lactic-co-glycolic acid) (PLGA) coatings were developed to explore the potential application of dexamethasone-eluting stents. Dexamethasone-eluting PLGA stents were prepared using ultrasonic atomization spray method. For other tests like stability and cytocompatibility and hemocompatibility tests, dexamethasone loaded coatings were deposited on 316L SS wafers. Fourier transform-infrared spectroscopy (FT-IR) results demonstrated that there was no chemical reaction between PLGA and dexamethasone. The balloon expansion experiment and surface morphology observation suggested that the stent coatings were smooth and uniform, and could also withstand the compressive and tensile strains imparted without cracking after stent expansion. The drug release behavior in vitro indicated that dexamethasone existed burst release within 1 day, but it presented linear release characteristics after 6 days. In vitro platelets adhesion, activation test and APTT test were also done, which showed that after blending dexamethasone into PLGA, the hemocompatibility was improved. Besides, dexamethasone and dexamethasone-loaded PLGA coatings could significantly inhibit the attachment and proliferation of smooth muscle cells.

Memantine loaded PLGA PEGylated nanoparticles for Alzheimer's disease: in vitro and in vivo characterization.

PubMed

Sánchez-López, Elena; Ettcheto, Miren; Egea, Maria Antonia; Espina, Marta; Cano, Amanda; Calpena, Ana Cristina; Camins, Antoni; Carmona, Nuria; Silva, Amélia M; Souto, Eliana B; García, Maria Luisa

2018-03-27

Memantine, drug approved for moderate to severe Alzheimer's disease, has not shown to be fully effective. In order to solve this issue, polylactic-co-glycolic (PLGA) nanoparticles could be a suitable solution to increase drug's action on the target site as well as decrease adverse effects. For these reason, Memantine was loaded in biodegradable PLGA nanoparticles, produced by double emulsion method and surface-coated with polyethylene glycol. MEM-PEG-PLGA nanoparticles (NPs) were aimed to target the blood-brain barrier (BBB) upon oral administration for the treatment of Alzheimer's disease. The production parameters were optimized by design of experiments. MEM-PEG-PLGA NPs showed a mean particle size below 200 nm (152.6 ± 0.5 nm), monomodal size distribution (polydispersity index, PI < 0.1) and negative surface charge (- 22.4 mV). Physicochemical characterization of NPs confirmed that the crystalline drug was dispersed inside the PLGA matrix. MEM-PEG-PLGA NPs were found to be non-cytotoxic on brain cell lines (bEnd.3 and astrocytes). Memantine followed a slower release profile from the NPs against the free drug solution, allowing to reduce drug administration frequency in vivo. Nanoparticles were able to cross BBB both in vitro and in vivo. Behavioral tests carried out on transgenic APPswe/PS1dE9 mice demonstrated to enhance the benefit of decreasing memory impairment when using MEM-PEG-PLGA NPs in comparison to the free drug solution. Histological studies confirmed that MEM-PEG-PLGA NPs reduced β-amyloid plaques and the associated inflammation characteristic of Alzheimer's disease. Memantine NPs were suitable for Alzheimer's disease and more effective than the free drug.

Enhanced Biological Functions of Human Mesenchymal Stem-Cell Aggregates Incorporating E-Cadherin-Modified PLGA Microparticles.

PubMed

Zhang, Yan; Mao, Hongli; Gao, Chao; Li, Suhua; Shuai, Qizhi; Xu, Jianbin; Xu, Ke; Cao, Lei; Lang, Ren; Gu, Zhongwei; Akaike, Toshihiro; Yang, Jun

2016-08-01

Mesenchymal stem cells (MSCs) have emerged as a promising source of multipotent cells for various cell-based therapies due to their unique properties, and formation of 3D MSC aggregates has been explored as a potential strategy to enhance therapeutic efficacy. In this study, poly(lactic-co-glycolic acid) (PLGA) microparticles modified with human E-cadherin fusion protein (hE-cad-PLGA microparticles) have been fabricated and integrated with human MSCs to form 3D cell aggregates. The results show that, compared with the plain PLGA, the hE-cad-PLGA microparticles distribute within the aggregates more evenly and further result in a more significant improvement of cellular proliferation and secretion of a series of bioactive factors due to the synergistic effects from the bioactive E-cadherin fragments and the PLGA microparticles. Meanwhile, the hE-cad-PLGA microparticles incorporated in the aggregates upregulate the phosphorylation of epidermal growth factor receptors and activate the AKT and ERK1/2 signaling pathways in the MSCs. Additionally, the E-cadherin/β-catenin cellular membrane complex in the MSCs is markedly stimulated by the hE-cad-PLGA microparticles. Therefore, engineering 3D cell aggregates with hE-cad-PLGA microparticles can be a promising method for ex vivo multipotent stem-cell expansion with enhanced biological functions and may offer a novel route to expand multipotent stem-cell-based clinical applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microporous silk fibroin scaffolds embedding PLGA microparticles for controlled growth factor delivery in tissue engineering.

PubMed

Wenk, Esther; Meinel, Anne J; Wildy, Sarah; Merkle, Hans P; Meinel, Lorenz

2009-05-01

The development of prototype scaffolds for either direct implantation or tissue engineering purposes and featuring spatiotemporal control of growth factor release is highly desirable. Silk fibroin (SF) scaffolds with interconnective pores, carrying embedded microparticles that were loaded with insulin-like growth factor I (IGF-I), were prepared by a porogen leaching protocol. Treatments with methanol or water vapor induced water insolubility of SF based on an increase in beta-sheet content as analyzed by FTIR. Pore interconnectivity was demonstrated by SEM. Porosities were in the range of 70-90%, depending on the treatment applied, and were better preserved when methanol or water vapor treatments were prior to porogen leaching. IGF-I was encapsulated into two different types of poly(lactide-co-glycolide) microparticles (PLGA MP) using uncapped PLGA (50:50) with molecular weights of either 14 or 35 kDa to control IGF-I release kinetics from the SF scaffold. Embedded PLGA MP were located in the walls or intersections of the SF scaffold. Embedment of the PLGA MP into the scaffolds led to more sustained release rates as compared to the free PLGA MP, whereas the hydrolytic degradation of the two PLGA MP types was not affected. The PLGA types used had distinct effects on IGF-I release kinetics. Particularly the supernatants of the lower molecular weight PLGA formulations turned out to release bioactive IGF-I. Our studies justify future investigations of the developed constructs for tissue engineering applications.

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

PubMed

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

2015-01-01

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). To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin. 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. 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. ISTPPLG6 NPs can act as potential drug carriers for the oral

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

Osteointegration of PLGA implants with nanostructured or microsized β-TCP particles in a minipig model.

PubMed

Kulkova, Julia; Moritz, Niko; Suokas, Esa O; Strandberg, Niko; Leino, Kari A; Laitio, Timo T; Aro, Hannu T

2014-12-01

Bioresorbable suture anchors and interference screws have certain benefits over equivalent titanium-alloy implants. However, there is a need for compositional improvement of currently used bioresorbable implants. We hypothesized that implants made of poly(l-lactide-co-glycolide) (PLGA) compounded with nanostructured particles of beta-tricalcium phosphate (β-TCP) would induce stronger osteointegration than implants made of PLGA compounded with microsized β-TCP particles. The experimental nanostructured self-reinforced PLGA (85L:15G)/β-TCP composite was made by high-energy ball-milling. Self-reinforced microsized PLGA (95L:5G)/β-TCP composite was prepared by melt-compounding. The composites were characterized by gas chromatography, Ubbelohde viscometry, scanning electron microscopy, laser diffractometry, and standard mechanical tests. Four groups of implants were prepared for the controlled laboratory study employing a minipig animal model. Implants in the first two groups were prepared from nanostructured and microsized PLGA/β-TCP composites respectively. Microroughened titanium-alloy (Ti6Al4V) implants served as positive intra-animal control, and pure PLGA implants as negative control. Cone-shaped implants were inserted in a random order unilaterally in the anterior cortex of the femoral shaft. Eight weeks after surgery, the mechanical strength of osteointegration of the implants was measured by a push-out test. The quality of new bone surrounding the implant was assessed by microcomputed tomography and histology. Implants made of nanostructured PLGA/β-TCP composite did not show improved mechanical osteointegration compared with the implants made of microsized PLGA/β-TCP composite. In the intra-animal comparison, the push-out force of two PLGA/β-TCP composites was 35-60% of that obtained with Ti6Al4V implants. The implant materials did not result in distinct differences in quality of new bone surrounding the implant. Copyright © 2014 Elsevier Ltd. All

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

Single oral dose of cannabinoid derivate loaded PLGA nanocarriers relieves neuropathic pain for eleven days.

PubMed

Berrocoso, Esther; Rey-Brea, Raquel; Fernández-Arévalo, Mercedes; Micó, Juan Antonio; Martín-Banderas, Lucía

2017-11-01

Neuropathic pain, resistant to opiates and other drugs, is a chronic/persistent state with a complex treatment and often poor efficacy. In this scenario, cannabinoids are increasingly regarded as a genuine alternative. In this paper, and in an experimental animal model of neuropathic pain, we studied the efficacy of three kinds of PLGA nanoparticles containing synthetic cannabinoid CB13: (i) plain nanoparticles (PLGA); (ii) particles coated with PEG chains (PLGA+PEG) and (iii) particles possessing hydrophilic surfaces obtained by covalently binding PEG chains (PLGA-PEG). The optimized formulation, CB13-PLGA-PEG, showed high drug loading (13%) and small size (<300nm) with a narrow distribution and controlled surface properties (near-neutral zeta potential and stable PEG corona). Animal nociceptive behavioral studies were conducted by paw pressure and acetone tests. Versus the free CB13, CB13-PLGA-PEG nanoparticles showed a very noticeable analgesic efficacy with the longest sustained pain-relieving effect, lasting up to eleven days after one oral dose. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of VEGF-loaded PLGA matrices in association with mesenchymal stem cells for tissue engineering

PubMed Central

Rosa, A.R.; Steffens, D.; Santi, B.; Quintiliano, K.; Steffen, N.; Pilger, D.A.; Pranke, P.

2017-01-01

The association of bioactive molecules, such as vascular endothelial growth factor (VEGF), with nanofibers facilitates their controlled release, which could contribute to cellular migration and differentiation in tissue regeneration. In this research, the influence of their incorporation on a polylactic-co-glycolic acid (PLGA) scaffold produced by electrospinning on cell adhesion and viability and cytotoxicity was carried out in three groups: 1) PLGA/BSA/VEGF; 2) PLGA/BSA, and 3) PLGA. Morphology, fiber diameter, contact angle, loading efficiency and controlled release of VEGF of the biomaterials, among others, were measured. The nanofibers showed smooth surfaces without beads and with interconnected pores. PLGA/BSA/VEGF showed the smallest water contact angle and VEGF released for up to 160 h. An improvement in cell adhesion was observed for the PLGA/BSA/VEGF scaffolds compared to the other groups and the scaffolds were non-toxic for the cells. Therefore, the scaffolds were shown to be a good strategy for sustained delivery of VEGF and may be a useful tool for tissue engineering. PMID:28793048

Effect of recombinant galectin-1 on the growth of immortal rat chondrocyte on chitosan-coated PLGA scaffold.

PubMed

Chen, Shiang-Jiuun; Lin, Chien-Chung; Tuan, Wei-Cheh; Tseng, Ching-Shiow; Huang, Rong-Nan

2010-06-15

The effect of galectin-1 (GAL1) on the growth of immortal rat chondrocyte (IRC) on chitosan-modified PLGA scaffold is investigated. The experimental results showed that water absorption ratio of chitosan-modified PLGA scaffold was 70% higher than that of PLGA alone after immersion in ddH(2)O for 2 weeks, indicating that chitosan-modification significantly enhances the hydrophilicity of PLGA. The experimental results also showed that GALl efficiently and spontaneously coats the chitosan-PLGA scaffold surface to promote adhesion and growth of immortal rat chondrocyte (IRC). To investigate the effect of endogenous GAL1, the full-length GAL1 cDNAs were cloned and constructed into pcDNA3.1 vectors to generate a plasmid expressed in IRC (IRC-GAL1). The results showed that IRC-GAL1 growth was significantly higher than that of IRC on chitosan-PLGA scaffold. The GAL1-potentiated IRC growth on chitosan-PLGA scaffold was dose-dependently inhibited by TDG (specific inhibitor of GAL1 binding). These results strongly suggest that GAL1 is critical for enhancing IRC cell adhesion and growth on chitosan-PLGA scaffold. Moreover, GAL1-coating or expression tends to promote IRC cell-cell aggregation on chitosan-PLGA scaffold and significantly enhances IRC migration. These results suggest that GAL1 probably could induce tissue differentiation and facilitates cartilage reconstruction. In conclusion, the experimental results suggest that both GAL1 and chitosan are important for enhancing IRC cell adhesion and growth on PLGA scaffold, and GAL1 is a potential biomaterial for tissue engineering. (c) 2009 Wiley Periodicals, Inc.

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

Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response.

PubMed

Javiya, Curie; Jonnalagadda, Sriramakamal

2016-09-01

The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis - TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. The spray dried particles were spherical, with a size range of about 2-3 µm and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 °C (enthalpy: 170.61 J/g) and a degradation-onset of 180 °C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 °C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 °C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection.

Kinetically Controlled Synthesis of Pt-Based One-Dimensional Hierarchically Porous Nanostructures with Large Mesopores as Highly Efficient ORR Catalysts

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

Fu, Shaofang; Zhu, Chengzhou; Song, Junhua

2016-12-28

Rational design and construction of Pt-based porous nanostructures with large mesopores have triggered significant considerations because of their high surface area and more efficient mass transport. Hydrochloric acid-induced kinetic reduction of metal precursors in the presence of soft template F-127 and hard template tellurium nanowires has been successfully demonstrated to construct one-dimensional hierarchical porous PtCu alloy nanostructures with large mesopores. Moreover, the electrochemical experiments demonstrated that the resultant PtCu hierarchically porous nanostructures with optimized composition exhibit enhanced electrocatalytic performance for oxygen reduction reaction.

Kinetically Controlled Synthesis of Pt-Based One-Dimensional Hierarchically Porous Nanostructures with Large Mesopores as Highly Efficient ORR Catalysts.

PubMed

Fu, Shaofang; Zhu, Chengzhou; Song, Junhua; Engelhard, Mark H; Xia, Haibing; Du, Dan; Lin, Yuehe

2016-12-28

Rational design and construction of Pt-based porous nanostructures with large mesopores have triggered significant considerations because of their high surface area and more efficient mass transport. Hydrochloric acid-induced kinetically controlled reduction of metal precursors in the presence of soft template F-127 and hard template tellurium nanowires has been successfully demonstrated to construct one-dimensional hierarchical porous PtCu alloy nanostructures with large mesopores. Moreover, the electrochemical experiments demonstrated that the PtCu hierarchically porous nanostructures synthesized under optimized conditions exhibit enhanced electrocatalytic performance for oxygen reduction reaction in acid media.

Large scale modulation of high frequency acoustic waves in periodic porous media.

PubMed

Boutin, Claude; Rallu, Antoine; Hans, Stephane

2012-12-01

This paper deals with the description of the modulation at large scale of high frequency acoustic waves in gas saturated periodic porous media. High frequencies mean local dynamics at the pore scale and therefore absence of scale separation in the usual sense of homogenization. However, although the pressure is spatially varying in the pores (according to periodic eigenmodes), the mode amplitude can present a large scale modulation, thereby introducing another type of scale separation to which the asymptotic multi-scale procedure applies. The approach is first presented on a periodic network of inter-connected Helmholtz resonators. The equations governing the modulations carried by periodic eigenmodes, at frequencies close to their eigenfrequency, are derived. The number of cells on which the carrying periodic mode is defined is therefore a parameter of the modeling. In a second part, the asymptotic approach is developed for periodic porous media saturated by a perfect gas. Using the "multicells" periodic condition, one obtains the family of equations governing the amplitude modulation at large scale of high frequency waves. The significant difference between modulations of simple and multiple mode are evidenced and discussed. The features of the modulation (anisotropy, width of frequency band) are also analyzed.

Fabrication and evaluation of a sustained-release chitosan-based scaffold embedded with PLGA microspheres.

PubMed

Song, Kedong; Liu, Yingchao; Macedo, Hugo M; Jiang, Lili; Li, Chao; Mei, Guanyu; Liu, Tianqing

2013-04-01

Nutrient depletion within three-dimensional (3D) scaffolds is one of the major hurdles in the use of this technology to grow cells for applications in tissue engineering. In order to help in addressing it, we herein propose to use the controlled release of encapsulated nutrients within polymer microspheres into chitosan-based 3D scaffolds, wherein the microspheres are embedded. This method has allowed maintaining a stable concentration of nutrients within the scaffolds over the long term. The polymer microspheres were prepared using multiple emulsions (w/o/w), in which bovine serum albumin (BSA) and poly (lactic-co-glycolic) acid (PLGA) were regarded as the protein pattern and the exoperidium material, respectively. These were then mixed with a chitosan solution in order to form the scaffolds by cryo-desiccation. The release of BSA, entrapped within the embedded microspheres, was monitored with time using a BCA kit. The morphology and structure of the PLGA microspheres containing BSA before and after embedding within the scaffold were observed under a scanning electron microscope (SEM). These had a round shape with diameters in the range of 27-55 μm, whereas the chitosan-based scaffolds had a uniform porous structure with the microspheres uniformly dispersed within their 3D structure and without any morphological change. In addition, the porosity, water absorption and degradation rate at 37 °C in an aqueous environment of 1% chitosan-based scaffolds were (92.99±2.51) %, (89.66±0.66) % and (73.77±3.21) %, respectively. The studies of BSA release from the embedded microspheres have shown a sustained and cumulative tendency with little initial burst, with (20.24±0.83) % of the initial amount released after 168 h (an average rate of 0.12%/h). The protein concentration within the chitosan-based scaffolds after 168 h was found to be (11.44±1.81)×10(-2) mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a promising technique

Enhancement of stem cell differentiation to osteogenic lineage on hydroxyapatite-coated hybrid PLGA/gelatin nanofiber scaffolds.

PubMed

Sanaei-Rad, Parisa; Jafarzadeh Kashi, Tahereh-Sadat; Seyedjafari, Ehsan; Soleimani, Masoud

2016-11-01

A combination of polymeric materials and bioceramics has recently received a great deal of attention for bone tissue engineering applications. In the present study, hybrid nanofibrous scaffolds were fabricated from PLGA and gelatin via electrospinning and then were coated with hydroxyapatite (HA). They were then characterized and used in stem cell culture studies for the evaluation of their biological behavior and osteogenic differentiation in vitro. This study showed that all PLGA, hybrid PLGA/gelatin and HA-PLGA/gelatin scaffolds were composed of ultrafine fibers with smooth morphology and interconnected pores. The MTT assay confirmed that the scaffolds can support the attachment and proliferation of stem cells. During osteogenic differentiation, bone-related gene expression, ALP activity and biomineralization on HA-PLGA/gelatin scaffolds were higher than those observed on other scaffolds and TCPS. PLGA/gelatin electrospun scaffolds also showed higher values of these markers than TCPS. Taking together, it was shown that nanofibrous structure enhanced osteogenic differentiation of adipose-tissue derived stem cells. Furthermore, surface-coated HA stimulated the effect of nanofibers on the commitment of stem cells toward osteolineage. In conclusion, HA-PLGA/gelatin electrospun scaffolds were demonstrated to have significant potential for bone tissue engineering applications. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Copper oxide loaded PLGA nanospheres: towards a multifunctional nanoscale platform for ultrasound-based imaging and therapy

NASA Astrophysics Data System (ADS)

Perlman, Or; Weitz, Iris S.; Sivan, Sarit S.; Abu-Khalla, Hiba; Benguigui, Madeleine; Shaked, Yuval; Azhari, Haim

2018-05-01

Copper oxide nanoparticles (CuO-NPs) are increasingly becoming the subject of investigation exploring their potential use for diagnostic and therapeutic purposes. Recent work has demonstrated their anticancer potential, as well as contrast agent capabilities for magnetic resonance imaging (MRI) and through-transmission ultrasound. However, no capability of CuO-NPs has been demonstrated using conventional ultrasound systems, which, unlike the former, are widely deployed in the clinic. Furthermore, in spite of their potential as multifunctional nano-based materials for diagnosis and therapy, CuO-NPs have been delayed from further clinical application due to their inherent toxicity. Herein, we present the synthesis of a novel nanoscale system, composed of CuO-loaded PLGA nanospheres (CuO-PLGA-NS), and demonstrate its imaging detectability and augmented heating effect by therapeutic ultrasound. The CuO-PLGA-NS were prepared by a double emulsion (W/O/W) method with subsequent solvent evaporation. They were characterized as sphere-shaped, with size approximately 200 nm. Preliminary results showed that the viability of PANC-1, human pancreatic adenocarcinoma cells was not affected after 72 h exposure to CuO-PLGA-NS, implying that PLGA masks the toxic effects of CuO-NPs. A systematic ultrasound imaging evaluation of CuO-PLGA-NS, using a conventional system, was performed in vitro and ex vivo using poultry heart and liver, and also in vivo using mice, all yielding a significant contrast enhancement. In contrast to CuO-PLGA-NS, neither bare CuO-NPs nor blank PLGA-NS possess these unique advantageous ultrasonic properties. Furthermore, CuO-PLGA-NS accelerated ultrasound-induced temperature elevation by more than 4 °C within 2 min. The heating efficiency (cumulative equivalent minutes at 43 °C) was increased approximately six-fold, demonstrating the potential for improved ultrasound ablation. In conclusion, CuO-PLGA-NS constitute a versatile platform, potentially useful for

Mn2+-coordinated PDA@DOX/PLGA nanoparticles as a smart theranostic agent for synergistic chemo-photothermal tumor therapy.

PubMed

Xi, Juqun; Da, Lanyue; Yang, Changshui; Chen, Rui; Gao, Lizeng; Fan, Lei; Han, Jie

2017-01-01

Nanoparticle drug delivery carriers, which can implement high performances of multi-functions, are of great interest, especially for improving cancer therapy. Herein, we reported a new approach to construct Mn 2+ -coordinated doxorubicin (DOX)-loaded poly(lactic- co -glycolic acid) (PLGA) nanoparticles as a platform for synergistic chemo-photothermal tumor therapy. DOX-loaded PLGA (DOX/PLGA) nanoparticles were first synthesized through a double emulsion-solvent evaporation method, and then modified with polydopamine (PDA) through self-polymerization of dopamine, leading to the formation of PDA@DOX/PLGA nanoparticles. Mn 2+ ions were then coordinated on the surfaces of PDA@DOX/PLGA to obtain Mn 2+ -PDA@DOX/PLGA nanoparticles. In our system, Mn 2+ -PDA@DOX/PLGA nanoparticles could destroy tumors in a mouse model directly, by thermal energy deposition, and could also simulate the chemotherapy by thermal-responsive delivery of DOX to enhance tumor therapy. Furthermore, the coordination of Mn 2+ could afford the high magnetic resonance (MR) imaging capability with sensitivity to temperature and pH. The results demonstrated that Mn 2+ -PDA@ DOX/PLGA nanoparticles had a great potential as a smart theranostic agent due to their imaging and tumor-growth-inhibition properties.

Mn2+-coordinated PDA@DOX/PLGA nanoparticles as a smart theranostic agent for synergistic chemo-photothermal tumor therapy

PubMed Central

Xi, Juqun; Da, Lanyue; Yang, Changshui; Chen, Rui; Gao, Lizeng; Fan, Lei; Han, Jie

2017-01-01

Nanoparticle drug delivery carriers, which can implement high performances of multi-functions, are of great interest, especially for improving cancer therapy. Herein, we reported a new approach to construct Mn2+-coordinated doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a platform for synergistic chemo-photothermal tumor therapy. DOX-loaded PLGA (DOX/PLGA) nanoparticles were first synthesized through a double emulsion-solvent evaporation method, and then modified with polydopamine (PDA) through self-polymerization of dopamine, leading to the formation of PDA@DOX/PLGA nanoparticles. Mn2+ ions were then coordinated on the surfaces of PDA@DOX/PLGA to obtain Mn2+-PDA@DOX/PLGA nanoparticles. In our system, Mn2+-PDA@DOX/PLGA nanoparticles could destroy tumors in a mouse model directly, by thermal energy deposition, and could also simulate the chemotherapy by thermal-responsive delivery of DOX to enhance tumor therapy. Furthermore, the coordination of Mn2+ could afford the high magnetic resonance (MR) imaging capability with sensitivity to temperature and pH. The results demonstrated that Mn2+-PDA@ DOX/PLGA nanoparticles had a great potential as a smart theranostic agent due to their imaging and tumor-growth-inhibition properties. PMID:28479854

Surface Entrapment of Fibronectin on Electrospun PLGA Scaffolds for Periodontal Tissue Engineering

PubMed Central

Gritsch, Kerstin; Salles, Vincent; Attik, Ghania N.; Grosgogeat, Brigitte

2014-01-01

Abstract Nowadays, the challenge in the tissue engineering field consists in the development of biomaterials designed to regenerate ad integrum damaged tissues. Despite the current use of bioresorbable polyesters such as poly(l-lactide) (PLA), poly(d,l-lactide-co-glycolide) (PLGA), and poly-ɛ-caprolactone in soft tissue regeneration researches, their hydrophobic properties negatively influence the cell adhesion. Here, to overcome it, we have developed a fibronectin (FN)-functionalized electrospun PLGA scaffold for periodontal ligament regeneration. Functionalization of electrospun PLGA scaffolds was performed by alkaline hydrolysis (0.1 or 0.01 M NaOH). Then, hydrolyzed scaffolds were coated by simple deposition of an FN layer (10 μg/mL). FN coating was evidenced by X-ray photoelectron analysis. A decrease of contact angle and greater cell adhesion to hydrolyzed, FN-coated PLGA scaffolds were noticed. Suitable degradation behavior without pH variations was observed for all samples up to 28 days. All treated materials presented strong shrinkage, fiber orientation loss, and collapsed fibers. However, functionalization process using 0.01 M NaOH concentration resulted in unchanged scaffold porosity, preserved chemical composition, and similar mechanical properties compared with untreated scaffolds. The proposed simplified method to functionalize electrospun PLGA fibers is an efficient route to make polyester scaffolds more biocompatible and shows potential for tissue engineering. PMID:24940563

Polysorbate 80-coated PLGA nanoparticles improve the permeability of acetylpuerarin and enhance its brain-protective effects in rats.

PubMed

Sun, Deqing; Xue, Aiying; Zhang, Bin; Lou, Haiyan; Shi, Huanying; Zhang, Xiumei

2015-12-01

Acetylpuerarin (AP) is an acetylated derivative of puerarin (PUE). The study aimed to prepare polysorbate 80-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles to improve the permeability of AP across the blood-brain barrier (BBB) and enhance its brain-protective effects. AP-loaded PLGA nanoparticles (AP-PLGA-NPs) were prepared using a solvent diffusion methodology. The NPs were characterized. The pharmacokinetics, tissue distributions and brain-protective effects of AP-PLGA-NPs were evaluated in animals. AP-PLGA-NPs were successfully prepared with a mean particle size of 145.0 nm and a zeta potential of -14.81 mV. The in-vitro release of AP from the PLGA-NPs showed a biphasic release profile. AP was metabolized into PUE in rats. The AUC0-∞ values of AP and PUE for AP-PLGA-NPs were 2.90- and 2.29-fold as great as those for AP solution, respectively. The values of the relative targeting efficiency in the brain were 2.40 and 2.58 for AP and PUE, and the ratios of peak concentration were 1.91 and 1.89 for AP and PUE, respectively. Compared with the crude drug, AP-PLGA-NPs showed better brain-protective effects in rats. Polysorbate 80-coated PLGA-NPs can improve the permeability of AP cross the BBB and enhance its brain-protective effects in rats. © 2015 Royal Pharmaceutical Society.

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.

Processing of large grain Y-123 superconductors with pre-defined porous structures

NASA Astrophysics Data System (ADS)

Sudhakar Reddy, E.; Babu, N. Hari; Shi, Y.; Cardwell, D. A.; Schmitz, G. J.

2005-02-01

Porous superconductors have inherent cooling advantages over their bulk counterparts and, as a result, are emerging as an important class of materials for practical applications. Single-domain Y-Ba-Cu-O (YBCO) foams processed with a pre-defined, open porous structure, for example, have significant potential for use as elements in resistive superconducting fault current limiters. In this case, the interconnected porosity is ideal for producing reinforced composites with improved mechanical and heat conducting properties. In this paper we describe a few simple methods for fabricating large grain YBCO superconductors with various predefined porous structures via an infiltration process from tailored, porous Y2BaCuO5 (Y-211) pre-forms manufactured by a variety of techniques, including slurry-coating of standard polyurethane foams to replicate their structure. Foams produced by this method typically have a strut thickness of a few hundred µm and pore sizes ranging from 10 to 100 pores per inch (PPI). Foams with increased strut thickness of up to millimetre dimensions can be produced by embedding organic ball spacers within the Y-211 pre-form followed by a burn-out and sintering process. Single-domain YBCO bulk materials with cellular and pre-defined 3D interconnected porosity may be produced by a similar process using tailored wax structures in Y-211 castings.

Enhanced intracellular delivery and controlled drug release of magnetic PLGA nanoparticles modified with transferrin.

PubMed

Cui, Yan-Na; Xu, Qing-Xing; Davoodi, Pooya; Wang, De-Ping; Wang, Chi-Hwa

2017-06-01

Owing to the presence of multidrug resistance in tumor cells, conventional chemotherapy remains clinically intractable. To enhance the therapeutic efficacy of chemotherapeutic agents, targeting strategies based on magnetic polymeric nanoparticles modified with targeting ligands have gained significant attention in cancer therapy. In this study, we synthesized transferrin (Tf)-modified poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NPs) loaded with paclitaxel (PTX) and superparamagnetic nanoparticle (MNP) using a solid-in-oil-in-water solvent evaporation method, followed by Tf adsorption on the surface of NPs. The Tf-modified magnetic PLGA NPs were characterized in terms of particle morphology and size, magnetic properties, encapsulation efficiency and drug release. Furthermore, the cytotoxicity and cellular uptake of the drug-loaded magnetic PLGA NPs were evaluated in both MCF-7 breast cancer and U-87 glioma cells in vitro. We found that Tf-modified PTX-MNP-PLGA NPs showed the highest cytotoxicity effect and cellular uptake efficiency under Tf receptor mediation in both MCF-7 and U-87 cells compared to unmodified PLGA NPs and free PTX. The cellular uptake efficiency of Tf-modified magnetic PLGA NPs appeared to be facilitated by the applied magnetic field, but the difference did not reach statistical significance. This study illustrates that this proposed formulation can be used as one new alternative treatment for patients bearing inaccessible tumors.

Enhanced intracellular delivery and controlled drug release of magnetic PLGA nanoparticles modified with transferrin

PubMed Central

Cui, Yan-na; Xu, Qing-xing; Davoodi, Pooya; Wang, De-ping; Wang, Chi-Hwa

2017-01-01

Owing to the presence of multidrug resistance in tumor cells, conventional chemotherapy remains clinically intractable. To enhance the therapeutic efficacy of chemotherapeutic agents, targeting strategies based on magnetic polymeric nanoparticles modified with targeting ligands have gained significant attention in cancer therapy. In this study, we synthesized transferrin (Tf)-modified poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NPs) loaded with paclitaxel (PTX) and superparamagnetic nanoparticle (MNP) using a solid-in-oil-in-water solvent evaporation method, followed by Tf adsorption on the surface of NPs. The Tf-modified magnetic PLGA NPs were characterized in terms of particle morphology and size, magnetic properties, encapsulation efficiency and drug release. Furthermore, the cytotoxicity and cellular uptake of the drug-loaded magnetic PLGA NPs were evaluated in both MCF-7 breast cancer and U-87 glioma cells in vitro. We found that Tf-modified PTX-MNP-PLGA NPs showed the highest cytotoxicity effect and cellular uptake efficiency under Tf receptor mediation in both MCF-7 and U-87 cells compared to unmodified PLGA NPs and free PTX. The cellular uptake efficiency of Tf-modified magnetic PLGA NPs appeared to be facilitated by the applied magnetic field, but the difference did not reach statistical significance. This study illustrates that this proposed formulation can be used as one new alternative treatment for patients bearing inaccessible tumors. PMID:28552909

Microencapsulation of curcumin in PLGA microcapsules by coaxial flow focusing

NASA Astrophysics Data System (ADS)

Lei, Fan; Si, Ting; Luo, Xisheng; Xu, Ronald X.

2014-03-01

Curcumin-loaded PLGA microcapsules are fabricated by a liquid-driving coaxial flow focusing device. In the process, a stable coaxial cone-jet configuration is formed under the action of a coflowing liquid stream and the coaxial liquid jet eventually breaks up into microcapsules because of flow instability. This process can be well controlled by adjusting the flow rates of three phases including the driving PVA water solution, the outer PLGA ethyl acetate solution and the inner curcumin propylene glycol solution. Confocal and SEM imaging methods clearly indicate the core-shell structure of the resultant microcapsules. The encapsulation rate of curcumin in PLGA is measured to be more than 70%, which is much higher than the tranditional methods such as emulsion. The size distribution of resultant microcapsules under different conditions is presented and compared. An in vitro release simulation platform is further developed to verify the feasibility and reliability of the method.

A mPEG-PLGA-b-PLL copolymer carrier for adriamycin and siRNA delivery.

PubMed

Liu, Peifeng; Yu, Hui; Sun, Ying; Zhu, Mingjie; Duan, Yourong

2012-06-01

A amphiphilic block copolymer composed of conventional monomethoxy (polyethylene glycol)-poly (d,l-lactide-co-glycolide)-poly (l-lysine) (mPEG-PLGA-b-PLL) was synthesized. The chemical structure of this copolymer and its precursors was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), (1)H Nuclear Magnetic Resonance ((1)H NMR) and Gel Permeation Chromatography (GPC). The copolymer was used to prepare nanoparticles (NPs) that were then loaded with either the anti-cancer drug adriamycin or small interfering RNA-negative (siRNA) using a double emulsion method. MTT assays used to study the in vitro cytotoxicity of mPEG-PLGA-b-PLL NPs showed that these particles were not toxic in huh-7 hepatic carcinoma cells. Confocal laser scanning microscopy (CLSM) and flow cytometer analysis results demonstrated efficient mPEG-PLGA-b-PLL NPs-mediated delivery of both adriamycin and siRNA into the cells. In vivo the targeting delivery of adriamycin or siRNA mediated by mPEG-PLGA-b-PLL NPs in the huh-7 hepatic carcinoma-bearing mice was evaluated using a fluorescence imaging system. The targeting delivery results and froze section analysis confirmed that drug or siRNA is deliver to tumor more efficiently by mPEG-PLGA-b-PLL NPs than free drug or Lipofectamine™2000. The high efficiency delivery of mPEG-PLGA-b-PLL NPs mainly due to the enhancement of cellular uptake. These results imply that mPEG-PLGA-b-PLL NPs have a great potential to be used as an effective carriers for adriamycin or siRNA. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Preparation, characterization, and biodistribution of letrozole loaded PLGA nanoparticles in Ehrlich Ascites tumor bearing mice.

PubMed

Mondal, Nita; Halder, Kamal Krishna; Kamila, Madan Mohan; Debnath, Mita Chatterjee; Pal, Tapan K; Ghosal, Saroj K; Sarkar, Bharat R; Ganguly, Shantanu

2010-09-15

Letrozole (LTZ) incorporated PLGA nanoparticles were prepared by solvent displacement technique and characterized by transmission electron microscopy, poly-dispersity index and zeta potential measurement. Radiolabeling of free LTZ and LTZ-loaded PLGA NPs was performed with technetium-99m with high labeling efficiency. The labeled complex showed good in vitro stability as verified by DTPA challenge test. The labeled complexes also showed significant in vivo stability when incubated in rat serum for 24 h. Biodistribution studies of (99m)Tc-labeled complexes were performed after intravenous administration in normal mice and Ehrlich Ascites tumor bearing mice. Compared to free LTZ, LTZ-loaded PLGA NPs exhibited significantly lower uptake by the organs of RES. The tumor concentration of LTZ-loaded PLGA NPs was 4.65 times higher than that of free LTZ at 4 h post-injection. This study indicates the capability of PLGA nanopartcles in enhancing the tumor uptake of letrozole. Copyright 2010 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-04-01

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

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

PubMed

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.

Cartilage repair using mesenchymal stem cell (MSC) sheet and MSCs-loaded bilayer PLGA scaffold in a rabbit model.

PubMed

Qi, Yiying; Du, Yi; Li, Weixu; Dai, Xuesong; Zhao, Tengfei; Yan, Weiqi

2014-06-01

The integration of regenerated cartilage with surrounding native cartilage is a major challenge for the success of cartilage tissue-engineering strategies. The purpose of this study is to investigate whether incorporation of the power of mesenchymal stem cell (MSC) sheet to MSCs-loaded bilayer poly-(lactic-co-glycolic acid) (PLGA) scaffolds can improve the integration and repair of cartilage defects in a rabbit model. Rabbit bone marrow-derived MSCs were cultured and formed cell sheet. Full-thickness cylindrical osteochondral defects (4 mm in diameter, 3 mm in depth) were created in the patellar groove of 18 New Zealand white rabbits and the osteochondral defects were treated with PLGA scaffold (n = 6), PLGA/MSCs (n = 6) or MSC sheet-encapsulated PLGA/MSCs (n = 6). After 6 and 12 weeks, the integration and tissue response were evaluated histologically. The MSC sheet-encapsulated PLGA/MCSs group showed significantly more amounts of hyaline cartilage and higher histological scores than PLGA/MSCs group and PLGA group (P < 0.05). In addition, the MSC sheet-encapsulated PLGA/MCSs group showed the best integration between the repaired cartilage and surrounding normal cartilage and subchondral bone compared to other two groups. The novel method of incorporation of MSC sheet to PLGA/MCSs could enhance the ability of cartilage regeneration and integration between repair cartilage and the surrounding cartilage. Transplantation of autologous MSC sheet combined with traditional strategies or cartilage debris might provide therapeutic opportunities for improving cartilage regeneration and integration in humans.

Micro/Nano Multilayered Scaffolds of PLGA and Collagen by Alternately Electrospinning for Bone Tissue Engineering

NASA Astrophysics Data System (ADS)

Kwak, Sanghwa; Haider, Adnan; Gupta, Kailash Chandra; Kim, Sukyoung; Kang, Inn-Kyu

2016-07-01

The dual extrusion electrospinning technique was used to fabricate multilayered 3D scaffolds by stacking microfibrous meshes of poly(lactic acid-co-glycolic acid) (PLGA) in alternate fashion to micro/nano mixed fibrous meshes of PLGA and collagen. To fabricate the multilayered scaffold, 35 wt% solution of PLGA in THF-DMF binary solvent (3:1) and 5 wt% solution of collagen in hexafluoroisopropanol (HFIP) with and without hydroxyapatite nanorods (nHA) were used. The dual and individual electrospinning of PLGA and collagen were carried out at flow rates of 1.0 and 0.5 mL/h, respectively, at an applied voltage of 20 kV. The density of collagen fibers in multilayered scaffolds has controlled the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. The homogeneous dispersion of glutamic acid-modified hydroxyapatite nanorods (nHA-GA) in collagen solution has improved the osteogenic properties of fabricated multilayered scaffolds. The fabricated multilayered scaffolds were characterized using FT-IR, X-ray photoelectron spectroscopy, and transmission electron microscopy (TEM). The scanning electron microscopy (FE-SEM) was used to evaluate the adhesion and spreads of MC3T3-E1 cells on multilayered scaffolds. The activity of MC3T3-E1 cells on the multilayered scaffolds was evaluated by applying MTT, alkaline phosphatase, Alizarin Red, von Kossa, and cytoskeleton F-actin assaying protocols. The micro/nano fibrous PLGA-Col-HA scaffolds were found to be highly bioactive in comparison to pristine microfibrous PLGA and micro/nano mixed fibrous PLGA and Col scaffolds.

PLGA/PFC particles loaded with gold nanoparticles as dual contrast agents for photoacoustic and ultrasound imaging

NASA Astrophysics Data System (ADS)

Wang, Yan J.; Strohm, Eric M.; Sun, Yang; Niu, Chengcheng; Zheng, Yuanyi; Wang, Zhigang; Kolios, Michael C.

2014-03-01

Phase-change contrast agents consisting of a perfluorocarbon (PFC) liquid core stabilized by a lipid, protein, or polymer shell have been proposed for a variety of clinical applications. Previous work has demonstrated that vaporization can be induced by laser irradiation through optical absorbers incorporated inside the droplet. In this study, Poly-lactide-coglycolic acid (PLGA) particles loaded with PFC liquid and silica-coated gold nanoparticles (GNPs) were developed and characterized using photoacoustic (PA) methods. Microsized PLGA particles were loaded with PFC liquid and GNPs (14, 35, 55nm each with a 20nm silica shell) using a double emulsion method. The PA signal intensity and optical vaporization threshold were investigated using a 375 MHz transducer and a focused 532-nm laser (up to 450-nJ per pulse). The laser-induced vaporization threshold energy decreased with increasing GNP size. The vaporization threshold was 850, 690 and 420 mJ/cm2 for 5μm-sized PLGA particles loaded with 14, 35 and 55 nm GNPs, respectively. The PA signal intensity increased as the laser fluence increased prior to the vaporization event. This trend was observed for all particles sizes. PLGA particles were then incubated with MDA-MB-231 breast cancer cells for 6 hours to investigate passive targeting, and the vaporization of the PLGA particles that were internalized within cells. The PLGA particles passively internalized by MDA cells were visualized via confocal fluorescence imaging. Upon PLGA particle vaporization, bubbles formed inside the cells resulting in cell destruction. This work demonstrates that GNPs-loaded PLGA/PFC particles have potential as PA theranostic agents in PA imaging and optically-triggered drug delivery systems.

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

PubMed

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

2014-01-01

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.

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

PubMed

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

2018-05-17

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

Superficially Porous Particles with 1000 Å Pores for Large Biomolecule High Performance Liquid Chromatography and Polymer Size Exclusion Chromatography

PubMed Central

Wagner, Brian M.; Schuster, Stephanie A.; Boyes, Barry E.; Shields, Taylor J.; Miles, William L.; Haynes, Mark J.; Moran, Robert E.; Kirkland, Joseph J.; Schure, Mark R.

2017-01-01

To facilitate mass transport and column efficiency, solutes must have free access to particle pores to facilitate interactions with the stationary phase. To ensure this feature, particles should be used for HPLC separations which have pores sufficiently large to accommodate the solute without restricted diffusion. This paper describes the design and properties of superficially porous (also called Fused-Core®, core shell or porous shell) particles with very large (1000 Å) pores specifically developed for separating very large biomolecules and polymers. Separations of DNA fragments, monoclonal antibodies, large proteins and large polystyrene standards are used to illustrate the utility of these particles for efficient, high-resolution applications. PMID:28213987

Ternary Aligned Nanofibers of RGD Peptide-Displaying M13 Bacteriophage/PLGA/Graphene Oxide for Facilitated Myogenesis

PubMed Central

Shin, Yong Cheol; Kim, Chuntae; Song, Su-Jin; Jun, Seungwon; Kim, Chang-Seok; Hong, Suck Won; Hyon, Suong-Hyu; Han, Dong-Wook; Oh, Jin-Woo

2018-01-01

Recently, there have been tremendous efforts to develop the biofunctional scaffolds by incorporating various biochemical factors. In the present study, we fabricated poly(lactic-co-glycolic acid) (PLGA) nanofiber sheets decorated with graphene oxide (GO) and RGD peptide. The decoration of GO and RGD peptide was readily achieved by using RGD peptide-displaying M13 bacteriophage (RGD-M13 phage) and electrospinning. Furthermore, the aligned GO-decorated PLGA/RGD peptide (GO-PLGA/RGD) ternary nanofiber sheets were prepared by magnetic field-assisted electrospinning, and their potentials as bifunctional scaffolds for facilitating myogenesis were explored. We characterized the physicochemical and mechanical properties of the sheets by scanning electron microscopy, Raman spectroscopy, contact angle measurement, and tensile test. In addition, the C2C12 skeletal myoblasts were cultured on the aligned GO-PLGA/RGD nanofiber sheets, and their cellular behaviors, including initial attachment, proliferation and myogenic differentiation, were evaluated. Our results revealed that the GO-PLGA/RGD nanofiber sheets had suitable physicochemical and mechanical properties for supporting cell growth, and could significantly promote the spontaneous myogenic differentiation of C2C12 skeletal myoblasts. Moreover, it was revealed that the myogenic differentiation was further accelerated on the aligned GO-PLGA/RGD nanofiber sheets due to the synergistic effects of RGD peptide, GO and aligned nanofiber structure. Therefore, , it is suggested that the aligned GO-PLGA/RGD ternary nanofiber sheets are one of the most promising approaches for facilitating myogenesis and promoting skeletal tissue regeneration. PMID:29577018

Ternary Aligned Nanofibers of RGD Peptide-Displaying M13 Bacteriophage/PLGA/Graphene Oxide for Facilitated Myogenesis.

PubMed

Shin, Yong Cheol; Kim, Chuntae; Song, Su-Jin; Jun, Seungwon; Kim, Chang-Seok; Hong, Suck Won; Hyon, Suong-Hyu; Han, Dong-Wook; Oh, Jin-Woo

2018-01-01

Recently, there have been tremendous efforts to develop the biofunctional scaffolds by incorporating various biochemical factors. In the present study, we fabricated poly(lactic- co -glycolic acid) (PLGA) nanofiber sheets decorated with graphene oxide (GO) and RGD peptide. The decoration of GO and RGD peptide was readily achieved by using RGD peptide-displaying M13 bacteriophage (RGD-M13 phage) and electrospinning. Furthermore, the aligned GO-decorated PLGA/RGD peptide (GO-PLGA/RGD) ternary nanofiber sheets were prepared by magnetic field-assisted electrospinning, and their potentials as bifunctional scaffolds for facilitating myogenesis were explored. We characterized the physicochemical and mechanical properties of the sheets by scanning electron microscopy, Raman spectroscopy, contact angle measurement, and tensile test. In addition, the C2C12 skeletal myoblasts were cultured on the aligned GO-PLGA/RGD nanofiber sheets, and their cellular behaviors, including initial attachment, proliferation and myogenic differentiation, were evaluated. Our results revealed that the GO-PLGA/RGD nanofiber sheets had suitable physicochemical and mechanical properties for supporting cell growth, and could significantly promote the spontaneous myogenic differentiation of C2C12 skeletal myoblasts. Moreover, it was revealed that the myogenic differentiation was further accelerated on the aligned GO-PLGA/RGD nanofiber sheets due to the synergistic effects of RGD peptide, GO and aligned nanofiber structure. Therefore, , it is suggested that the aligned GO-PLGA/RGD ternary nanofiber sheets are one of the most promising approaches for facilitating myogenesis and promoting skeletal tissue regeneration.

Formation of quasi-single crystalline porous ZnO nanostructures with a single large cavity

NASA Astrophysics Data System (ADS)

Cho, Seungho; Kim, Semi; Jung, Dae-Won; Lee, Kun-Hong

2011-09-01

We report a method for synthesizing quasi-single crystalline porous ZnO nanostructures containing a single large cavity. The microwave-assisted route consists of a short (about 2 min) temperature ramping stage (from room temperature to 120 °C) and a stage in which the temperature is maintained at 120 °C for 2 h. The structures produced by this route were 200-480 nm in diameter. The morphological yields of this method were very high. The temperature- and time-dependent evolution of the synthesized powders and the effects of an additive, vitamin C, were studied. Spherical amorphous/polycrystalline structures (70-170 nm in diameter), which appeared transitorily, may play a key role in the formation of the single crystalline porous hollow ZnO nanostructures. Studies and characterization of the nanostructures suggested a possible mechanism for formation of the quasi-single crystalline porous ZnO nanostructures with an interior space.We report a method for synthesizing quasi-single crystalline porous ZnO nanostructures containing a single large cavity. The microwave-assisted route consists of a short (about 2 min) temperature ramping stage (from room temperature to 120 °C) and a stage in which the temperature is maintained at 120 °C for 2 h. The structures produced by this route were 200-480 nm in diameter. The morphological yields of this method were very high. The temperature- and time-dependent evolution of the synthesized powders and the effects of an additive, vitamin C, were studied. Spherical amorphous/polycrystalline structures (70-170 nm in diameter), which appeared transitorily, may play a key role in the formation of the single crystalline porous hollow ZnO nanostructures. Studies and characterization of the nanostructures suggested a possible mechanism for formation of the quasi-single crystalline porous ZnO nanostructures with an interior space. Electronic supplementary information (ESI) available: TEM images and the corresponding SAED image of a Zn

Hyaluronic Acid-Modified Cationic Lipid-PLGA Hybrid Nanoparticles as a Nanovaccine Induce Robust Humoral and Cellular Immune Responses.

PubMed

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

2016-05-18

Here, we investigated the use of hyaluronic acid (HA)-decorated cationic lipid-poly(lactide-co-glycolide) acid (PLGA) hybrid nanoparticles (HA-DOTAP-PLGA NPs) as vaccine delivery vehicles, which were originally developed for the cytosolic delivery of genes. Our results demonstrated that after the NPs uptake by dendritic cells (DCs), some of the antigens that were encapsulated in HA-DOTAP-PLGA NPs escaped to the cytosolic compartment, and whereas some of the antigens remained in the endosomal/lysosomal compartment, where both MHC-I and MHC-II antigen presentation occurred. Moreover, HA-DOTAP-PLGA NPs led to the up-regulation of MHC, costimulatory molecules, and cytokines. In vivo experiments further revealed that more powerful immune responses were induced from mice immunized with HA-DOTAP-PLGA NPs when compared with cationic lipid-PLGA nanoparticles and free ovalbumin (OVA); the responses included antigen-specific CD4(+) and CD8(+) T-cell responses, the production of antigen-specific IgG antibodies and the generation of memory CD4(+) and CD8(+) T cells. Overall, these data demonstrate the high potential of HA-DOTAP-PLGA NPs for use as vaccine delivery vehicles to elevate cellular and humoral immune responses.

Combination of PLGA nanoparticles with mucoadhesive guar-gum films for buccal delivery of antihypertensive peptide.

PubMed

Castro, Pedro M; Baptista, Patrícia; Madureira, Ana Raquel; Sarmento, Bruno; Pintado, Manuela E

2018-05-22

Oral administration of proteins and peptides still is a challenging task to overcome due to low permeability through absorptive epithelia, degradation and metabolism that lead to poor bioavailability. Attempting to overcome such limitations, an antihypertensive peptide derived from whey protein, with KGYGGVSLPEW sequence, was incorporated for the first time into polymeric nanoparticles. An experimental design was followed in order to optimize drug-loading, association efficiency, mean particle size, zeta-potential and polydispersity index of a formulation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles as carriers for bioactive peptides. In sequence, peptide-loaded PLGA nanoparticles were incorporated in a guar-gum film matrix, resulting in a combined delivery system aiming to promote slow release and permeation across buccal epithelium. Neither PLGA nanoparticles, guar-gum films nor the conjugation of PLGA nanoparticles and guar-gum films (GfNp) significantly compromised in vitro TR146 human buccal carcinoma cell line viability after 12 h contact, as assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide reduction assay (MTT). In vitro release assay for developed formulations allowed to conclude that the combination of orodispersible film and nanoparticles granted a slower release of AhP when compared with PLGA or guar-gum films alone or with control. GfNp offered more effective, synergistic, in vitro permeation of TR146 cell multilayer in comparison with guar-gum films or PLGA nanoparticles alone. The combination of PLGA nanoparticles with guar-gum films represent a suitable alternative to conventional per os delivery systems, leading to an increased buccal permeability of carried antihypertensive peptide. Copyright © 2018 Elsevier B.V. All rights reserved.

RGD peptide-displaying M13 bacteriophage/PLGA nanofibers as cell-adhesive matrices for smooth muscle cells

NASA Astrophysics Data System (ADS)

Shin, Yong Cheol; Lee, Jong Ho; Jin, Oh Seong; Lee, Eun Ji; Jin, Lin Hua; Kim, Chang-Seok; Hong, Suck Won; Han, Dong-Wook; Kim, Chuntae; Oh, Jin-Woo

2015-01-01

Extracellular matrices (ECMs) are network structures that play an essential role in regulating cellular growth and differentiation. In this study, novel nanofibrous matrices were fabricated by electrospinning M13 bacteriophage and poly(lactic- co-glycolic acid) (PLGA) and were shown to be structurally and functionally similar to natural ECMs. A genetically-engineered M13 bacteriophage was constructed to display Arg-Gly-Asp (RGD) peptides on its surface. The physicochemical properties of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage)/PLGA nanofibers were characterized by using scanning electron microscopy and Fourier-transform infrared spectroscopy. We used immunofluorescence staining to confirm that M13 bacteriophages were homogenously distributed in RGD-M13 phage/PLGA matrices. Furthermore, RGD-M13 phage/PLGA nanofibrous matrices, having excellent biocompatibility, can enhance the behaviors of vascular smooth muscle cells. This result suggests that RGD-M13 phage/PLGA nanofibrous matrices have potentials to serve as tissue engineering scaffolds.

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.

Temozolomide-loaded PLGA nanoparticles to treat glioblastoma cells: a biophysical and cell culture evaluation.

PubMed

Ananta, Jeyarama S; Paulmurugan, Ramasamy; Massoud, Tarik F

2016-01-01

Current chemotherapies for brain glioblastoma do not achieve sufficient drug concentrations within tumors. Polymeric nanoparticles have useful physicochemical properties that make them promising as nanoparticle platforms for glioblastoma drug delivery. Poly[lactic-co-glycolic acid] (PLGA) nanoparticles encapsulating temozolomide (TMZ) could improve localized delivery and sustained drug release to glioblastomas. We investigated three different procedures to encapsulate TMZ within PLGA nanoparticles. We studied the biophysical features of optimized nanocarriers, including their size, shape, surface properties, and release characteristics of TMZ. We evaluated the antiproliferative and cytotoxic effects of TMZ-loaded PLGA nanoparticles on U87 MG glioblastoma cells. A single emulsion technique using a TMZ saturated aqueous phase produced nanoparticles ≤200 nm in size allowing a maximal drug loading of 4.4% w/w of polymer. There was a bi-phasic drug release pattern, with 80% of TMZ released within the first 6 h. Nanoparticles accumulated in the cytoplasm after effective endocytosis. There was no significant difference in cytotoxic effect of TMZ encapsulated within PLGA nanoparticles and free TMZ. PLGA nanoparticles are not suitable as carriers of TMZ for glioblastoma drug delivery on account of the overall high IC50 values of glioblastoma cells to TMZ and poor loading and encapsulation efficiencies. Further biotechnological developments aimed at improving the loading of TMZ in PLGA nanoparticles or co-delivery of small molecule sensitizers to improve the response of human glioblastoma cells to TMZ are required for this approach to be considered and optimized for future clinical translation.

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.

PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα

PubMed Central

Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena; Tian, Xuebi; Liu, Ying; Wang, Zaijie Jim

2016-01-01

Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin’s mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling. PMID:26744842

Superficially porous particles with 1000Å pores for large biomolecule high performance liquid chromatography and polymer size exclusion chromatography.

PubMed

Wagner, Brian M; Schuster, Stephanie A; Boyes, Barry E; Shields, Taylor J; Miles, William L; Haynes, Mark J; Moran, Robert E; Kirkland, Joseph J; Schure, Mark R

2017-03-17

To facilitate mass transport and column efficiency, solutes must have free access to particle pores to facilitate interactions with the stationary phase. To ensure this feature, particles should be used for HPLC separations which have pores sufficiently large to accommodate the solute without restricted diffusion. This paper describes the design and properties of superficially porous (also called Fused-Core ® , core shell or porous shell) particles with very large (1000Å) pores specifically developed for separating very large biomolecules and polymers. Separations of DNA fragments, monoclonal antibodies, large proteins and large polystyrene standards are used to illustrate the utility of these particles for efficient, high-resolution applications. Copyright © 2017 Elsevier B.V. All rights reserved.

In vivo evidence of oral vaccination with PLGA nanoparticles containing the immunostimulant monophosphoryl lipid A.

PubMed

Sarti, Federica; Perera, Glen; Hintzen, Fabian; Kotti, Katerina; Karageorgiou, Vassilis; Kammona, Olga; Kiparissides, Costas; Bernkop-Schnürch, Andreas

2011-06-01

Although oral vaccination has numerous advantages over the commonly used parenteral route, degradation of vaccine and its low uptake in the lymphoid tissue of the gastrointestinal (GI) tract still impede their development. In this study, the model antigen ovalbumin (OVA) and the immunostimulant monophosphoryl lipid A (MPLA) were incorporated in polymeric nanoparticles based on poly(D,L-lactide-co-glycolide) (PLGA). These polymeric carriers were orally administered to BALB/c mice (Bagg albino, inbred strain of mouse) and the resulting time-dependent systemic and mucosal immune responses towards OVA were assessed by measuring the OVA-specific IgG and IgA titers using an enzyme-linked immunosorbent assay (ELISA). PLGA nanoparticles were spherical in shape, around 320 nm in size, negatively charged (around -20 mV) and had an OVA and MPLA payload of 9.6% and 0.86%, respectively. A single immunization with formulation containing (OVA + MPLA) incorporated in PLGA nanoparticles induced a stronger IgG immune response than that induced by OVA in PBS solution or OVA incorporated into PLGA nanoparticles. Moreover, significantly higher IgA titers were generated by administration of (OVA + MPLA)/PLGA nanoparticles compared to IgA stimulated by control formulations, proving the capability of inducing a mucosal immunity. These findings demonstrate that co-delivery of OVA and MPLA in PLGA nanoparticles promotes both systemic and mucosal immune responses and represents therefore a suitable strategy for oral vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

NASA Astrophysics Data System (ADS)

Ding, Hong; Yong, Ken-Tye; Roy, Indrajit; Hu, Rui; Wu, Fang; Zhao, Lingling; Law, Wing-Cheung; Zhao, Weiwei; Ji, Wei; Liu, Liwei; Bergey, Earl J.; Prasad, Paras N.

2011-04-01

In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l - 1. Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the αvβ3 integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold

PubMed Central

Xin, Xuejun; Hussain, Mohammad; Mao, Jeremy J.

2010-01-01

Nanofibers have recently gained substantial interest for potential applications in tissue engineering. The objective of this study was to determine whether electrospun nanofibers accommodate the viability, growth, and differentiation of human mesenchymal stem cells (hMSCs) as well as their osteogenic (hMSC-Ob) and chondrogenic (hMSC-Ch) derivatives. Poly(D,L-lactide-co-glycolide) (PLGA) beads with a PLA:PGA ratio of 85:15 were electrospun into non-woven fibers with an average diameter of 760±210 nm. The average Young’s modulus of electrospun PLGA nanofibers was 42±26 kPa, per nanoindentation with atomic force microscopy (AFM). Human MSCs were seeded 1–4 weeks at a density of 2×106 cells/mL in PLGA nanofiber sheets. After 2 week culture on PLGA nanofiber scaffold, hMSCs remained as precursors upon immunoblotting with hKL12 antibody. SEM taken up to 7 days after cell seeding revealed that hMSCs, hMSC-Ob and hMSC-Ch apparently attached to PLGA nanofibers. The overwhelming majority of hMSCs was viable and proliferating in PLGA nanofiber scaffolds up to the tested 14 days, as assayed live/dead tests, DNA assay and BrdU. In a separate experiment, hMSCs seeded in PLGA nanofiber scaffolds were differentiated into chodrogenic and osteogenic cells. Histological assays revealed that hMSCs continuously differentiated into chondrogenic cells and osteogenic cells after 2 week incubation in PLGA nanofibers. Taken together, these data represent an original investigation of continuous differentiation of hMSCs into chondrogenic and osteogenic cells in PLGA nanofiber scaffold. Consistent with previous work, these findings also suggest that nanofibers may serve as accommodative milieu for not only hMSCs, but also as a 3D carrier vehicle for lineage specific cells. PMID:17010425

PLGA/nHA hybrid nanofiber scaffold as a nanocargo carrier of insulin for accelerating bone tissue regeneration

NASA Astrophysics Data System (ADS)

Haider, Adnan; Gupta, Kailash Chandra; Kang, Inn-Kyu

2014-06-01

The development of tissue engineering in the field of orthopedic surgery is booming. Two fields of research in particular have emerged: approaches for tailoring the surface properties of implantable materials with osteoinductive factors as well as evaluation of the response of osteogenic cells to these fabricated implanted materials (hybrid material). In the present study, we chemically grafted insulin onto the surface of hydroxyapatite nanorods (nHA). The insulin-grafted nHAs (nHA-I) were dispersed into poly(lactide-co-glycolide) (PLGA) polymer solution, which was electrospun to prepare PLGA/nHA-I composite nanofiber scaffolds. The morphology of the electrospun nanofiber scaffolds was assessed by field emission scanning electron microscopy (FESEM). After extensive characterization of the PLGA/nHA-I and PLGA/nHA composite nanofiber scaffolds by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectrometry (EDS), and transmission electron microscopy (TEM), the PLGA/nHA-I and PLGA/nHA (used as control) composite nanofiber scaffolds were subjected to cell studies. The results obtained from cell adhesion, alizarin red staining, and Von Kossa assay suggested that the PLGA/nHA-I composite nanofiber scaffold has enhanced osteoblastic cell growth, as more cells were proliferated and differentiated. The fact that insulin enhanced osteoblastic cell proliferation will open new possibilities for the development of artificial scaffolds for bone tissue regeneration.

Protein functionalized tramadol-loaded PLGA nanoparticles: preparation, optimization, stability and pharmacodynamic studies.

PubMed

Lalani, Jigar; Rathi, Mohan; Lalan, Manisha; Misra, Ambikanandan

2013-06-01

Poly (d,l-lactide-co-glycolide acid) (PLGA) Nanoparticles (NPs) with sustained drug release and enhanced circulation time presents widely explored non-invasive approach for drug delivery to brain. However, blood-brain barrier (BBB) limits the drug delivery to brain. This can be overcome by anchoring endogenous ligand like Transferrin (Tf) and Lactoferrin (Lf) on the surface of NPs, allowing efficient brain delivery via receptor-mediated endocytosis. The aim of the present investigation was preparation, optimization, characterization and comparative evaluation of targeting efficiency of Tf- vs. Lf-conjugated NPs. Tramadol-loaded PLGA NPs were prepared by nanoprecipitation techniques and optimized using 3(3) factorial design. The effect of polymer concentration, stabilizer concentration and organic:aqueous phase ratio were evaluated on particle size (PS) and entrapment efficiency (EE). The formulation was optimized based on desirability for lower PS (<150 nm) and higher EE (>70%). Optimized PLGA NPs were conjugated with Tf and Lf, characterized and evaluated for stability study. Pharmacodynamic study was performed in rat after intravenous administration. The optimized formulation had 100 mg of PLGA, 1% polyvinyl alcohol (PVA) and 1:2 acetone:water ratio. The Lf and Tf conjugation to PLGA NPs was estimated to 186 Tf and 185 Lf molecules per NPs. Lyophilization was optimized at 1:2 ratio of NPs:trehalose. The NPs were found stable for 6 months at refrigerated condition. Pharmacodynamic study demonstrated enhanced efficacy of ligand-conjugated NPs against unconjugated NPs. Conjugated NPs demonstrated significantly higher pharmacological effect over a period of 24 h. Furthermore Lf functionalized NPs exhibited better antinociceptive effect as compared to Tf functionalized NPs.

Electrospinning of PLGA/gum tragacanth nanofibers containing tetracycline hydrochloride for periodontal regeneration.

PubMed

Ranjbar-Mohammadi, Marziyeh; Zamani, M; Prabhakaran, M P; Bahrami, S Hajir; Ramakrishna, S

2016-01-01

Controlled drug release is a process in which a predetermined amount of drug is released for longer period of time, ranging from days to months, in a controlled manner. In this study, novel drug delivery devices were fabricated via blend electrospinning and coaxial electrospinning using poly lactic glycolic acid (PLGA), gum tragacanth (GT) and tetracycline hydrochloride (TCH) as a hydrophilic model drug in different compositions and their performance as a drug carrier scaffold was evaluated. Scanning electron microscopy (SEM) results showed that fabricated PLGA, blend PLGA/GT and core shell PLGA/GT nanofibers had a smooth and bead-less morphology with the diameter ranging from 180 to 460 nm. Drug release studies showed that both the fraction of GT within blend nanofibers and the core-shell structure can effectively control TCH release rate from the nanofibrous membranes. By incorporation of TCH into core-shell nanofibers, drug release was sustained for 75 days with only 19% of burst release within the first 2h. The prolonged drug release, together with proven biocompatibility, antibacterial and mechanical properties of drug loaded core shell nanofibers make them a promising candidate to be used as drug delivery system for periodontal diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

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

High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.

PubMed

Cun, Dongmei; Jensen, Ditte Krohn; Maltesen, Morten Jonas; Bunker, Matthew; Whiteside, Paul; Scurr, David; Foged, Camilla; Nielsen, Hanne Mørck

2011-01-01

Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties. Copyright © 2010 Elsevier B.V. All rights reserved.

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.

[Experiment of porous calcium phosphate/bone matrix gelatin composite cement for repairing lumbar vertebral bone defect in rabbit].

PubMed

Wang, Song; Yang, Han; Yang, Jian; Kang, Jianping; Wang, Qing; Song, Yueming

2017-12-01

To investigate the effect of a porous calcium phosphate/bone matrix gelatin (BMG) composite cement (hereinafter referred to as the "porous composite cement") for repairing lumbar vertebral bone defect in a rabbit model. BMG was extracted from adult New Zealand rabbits according to the Urist's method. Poly (lactic-co-glycolic) acid (PLGA) microsphere was prepared by W/O/W double emulsion method. The porous composite cement was developed by using calcium phosphate cement (CPC) composited with BMG and PLGA microsphere. The physicochemical characterizations of the porous composite cement were assessed by anti-washout property, porosity, and biomechanical experiment, also compared with the CPC. Thirty 2-month-old New Zealand rabbits were used to construct vertebral bone defect at L 3 in size of 4 mm×3 mm×3 mm. Then, the bone defect was repaired with porous composite cement (experimental group, n =15) or CPC (control group, n =15). At 4, 8, and 12 weeks after implantation, each bone specimen was assessed by X-ray films for bone fusion, micro-CT for bone mineral density (BMD), bone volume fraction (BVF), trabecular thickness (Tb. Th.), trabecular number (Tb.N.), and trabecular spacing (Tb. Sp.), and histological section with toluidine blue staining for new-born bone formation. The study demonstrated well anti-washout property in 2 groups. The porous composite cement has 55.06%±1.18% of porosity and (51.63±6.73) MPa of compressive strength. The CPC has 49.38%±1.75% of porosity and (63.34±3.27) MPa of compressive strength. There were significant differences in porosity and compressive strength between different cements ( t =4.254, P =0.006; t =2.476, P =0.034). X-ray films revealed that the zone between the cement and host bone gradually blurred with the time extending. At 12 weeks after implantation, the zone was disappeared in the experimental group, but clear in the control group. There were significant differences in BMD, BVF, Tb. Th., Tb. N., and Tb. Sp. between

Bioinspired large-scale aligned porous materials assembled with dual temperature gradients

PubMed Central

Bai, Hao; Chen, Yuan; Delattre, Benjamin; Tomsia, Antoni P.; Ritchie, Robert O.

2015-01-01

Natural materials, such as bone, teeth, shells, and wood, exhibit outstanding properties despite being porous and made of weak constituents. Frequently, they represent a source of inspiration to design strong, tough, and lightweight materials. Although many techniques have been introduced to create such structures, a long-range order of the porosity as well as a precise control of the final architecture remain difficult to achieve. These limitations severely hinder the scale-up fabrication of layered structures aimed for larger applications. We report on a bidirectional freezing technique to successfully assemble ceramic particles into scaffolds with large-scale aligned, lamellar, porous, nacre-like structure and long-range order at the centimeter scale. This is achieved by modifying the cold finger with a polydimethylsiloxane (PDMS) wedge to control the nucleation and growth of ice crystals under dual temperature gradients. Our approach could provide an effective way of manufacturing novel bioinspired structural materials, in particular advanced materials such as composites, where a higher level of control over the structure is required. PMID:26824062

In Vitro Comparative Study of Oxygen Plasma Treated Poly(Lactic⁻Co⁻Glycolic) (PLGA) Membranes and Supported Nanostructured Oxides for Guided Bone Regeneration Processes.

PubMed

Torres-Lagares, Daniel; Castellanos-Cosano, Lizett; Serrera-Figallo, Maria-Angeles; López-Santos, Carmen; Barranco, Angel; Rodríguez-González-Elipe, Agustín; Gutierrez-Perez, Jose-Luis

2018-05-08

(1) Background: The use of physical barriers to prevent the invasion of gingival and connective tissue cells into bone cavities during the healing process is called guided bone regeneration. The objective of this in-vitro study was to compare the growth of human osteoblasts on Poly(Lactic⁻co⁻Glycolic) (PLGA) membranes modified with oxygen plasma and Hydroxyapatite (HA), silicon dioxide (SiO₂), and titanium dioxide (TiO₂) composite nanoparticles, respectively. (2) Methods: All the membranes received a common treatment with oxygen plasma and were subsequently treated with HA nanostructured coatings (n = 10), SiO₂ (n = 10) and TiO₂ (n = 10), respectively and a PLGA control membrane (n = 10). The assays were performed using the human osteoblast line MG-63 acquired from the Center for Scientific Instrumentation (CIC) from the University of Granada. The cell adhesion and the viability of the osteoblasts were analyzed by means of light-field microphotographs of each condition with the inverted microscope Axio Observer A1 (Carl Zeiss). For the determination of the mitochondrial energy balance, the MitoProbe™ JC-1 Assay Kit was employed. For the determination of cell growth and the morphology of adherent osteoblasts, two techniques were employed: staining with phalloidin-TRITC and staining with DAPI. (3) Results: The modified membranes that show osteoblasts with a morphology more similar to the control osteoblasts follow the order: PLGA/PO₂/HA > PLGA/PO₂/SiO₂ > PLGA/PO₂/TiO₂ > PLGA ( p < 0.05). When analysing the cell viability, a higher percentage of viable cells bound to the membranes was observed as follows: PLGA/PO₂/SiO₂ > PLGA/PO₂/HA > PLGA/PO₂/TiO₂ > PLGA ( p < 0.05), with a better energy balance of the cells adhered to the membranes PLGA/PO₂/HA and PLGA/PO₂/SiO₂. (4) Conclusion: The membrane in which osteoblasts show characteristics more similar to the control osteoblasts is the PLGA/PO₂/HA, followed by the PLGA/PO₂/SiO₂.

Pore size regulates cell and tissue interactions with PLGA-CaP scaffolds used for bone engineering.

PubMed

Sicchieri, Luciana Gonçalves; Crippa, Grasiele Edilaine; de Oliveira, Paulo Tambasco; Beloti, Marcio Mateus; Rosa, Adalberto Luiz

2012-02-01

A common subject in bone tissue engineering is the need for porous scaffolds to support cell and tissue interactions aiming at repairing bone tissue. As poly(lactide-co-glycolide)-calcium phosphate (PLGA-CaP) scaffolds can be manufactured with different pore sizes, the aim of this study was to evaluate the effect of pore diameter on osteoblastic cell responses and bone tissue formation. Scaffolds were prepared with 85% porosity, with pore diameters in the ranges 470-590, 590-850 and 850-1200 µm. Rat bone marrow stem cells differentiated into osteoblasts were cultured on the scaffolds for up to 10 days to evaluate cell growth, alkaline phosphatase (ALP) activity and the gene expression of the osteoblast markers RUNX2, OSX, COL, MSX2, ALP, OC and BSP by real-time PCR. Scaffolds were implanted in critical size rat calvarial defects for 2, 4, and 8 weeks for histomorphometric analysis. Cell growth and ALP activity were not affected by the pore size; however, there was an increase in the gene expression of osteoblastic markers with the increase in the pore sizes. At 2 weeks all scaffolds displayed a similar amount of bone and blood vessels formation. At 4 and 8 weeks much more bone formation and an increased number of blood vessels were observed in scaffolds with pores of 470-590 µm. These results show that PLGA-CaP is a promising biomaterial for bone engineering. However, ideally, combinations of larger (-1000 µm) and smaller (-500 µm) pores in a single scaffold would optimize cellular and tissue responses during bone healing. Copyright © 2011 John Wiley & Sons, Ltd.

Treatment of Francisella infections via PLGA- and lipid-based nanoparticle delivery of antibiotics in a zebrafish model.

PubMed

Ulanova, Lilia S; Pinheiro, Marina; Vibe, Carina; Nunes, Claudia; Misaghian, Dorna; Wilson, Steven; Zhu, Kaizheng; Fenaroli, Federico; Winther-Larsen, Hanne C; Reis, Salette; Griffiths, Gareth

2017-06-19

We tested the efficiency of 2 different antibiotics, rifampicin and oxolinic acid, against an established infection caused by fish pathogen Francisella noatunensis ssp. orientalis (F.n.o.) in zebrafish. The drugs were tested in the free form as well as encapsulated into biodegradable nanoparticles, either polylactic-co-glycolic acid (PLGA) nanoparticles or nanostructured lipid carriers. The most promising therapies were PLGA-rifampicin nanoparticles and free oxolinic acid; the PLGA nanoparticles significantly delayed embryo mortality while free oxolinic acid prevented it. Encapsulation of rifampicin in both PLGA and nanostructured lipid carriers enhanced its efficiency against F.n.o. infection relative to the free drug. We propose that the zebrafish model is a robust, rapid system for initial testing of different treatments of bacterial diseases important for aquaculture.

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

Evaluation of a combined drug-delivery system for proteins assembled with polymeric nanoparticles and porous microspheres; characterization and protein integrity studies.

PubMed

Alcalá-Alcalá, Sergio; Benítez-Cardoza, Claudia G; Lima-Muñoz, Enrique J; Piñón-Segundo, Elizabeth; Quintanar-Guerrero, David

2015-07-15

This work presents an evaluation of the adsorption/infiltration process in relation to the loading of a model protein, α-amylase, into an assembled biodegradable polymeric system, free of organic solvents and made up of poly(D,L-lactide-co-glycolide) acid (PLGA). Systems were assembled in a friendly aqueous medium by adsorbing and infiltrating polymeric nanoparticles into porous microspheres. These assembled systems are able to load therapeutic amounts of the drug through adsorption of the protein onto the large surface area characteristic of polymeric nanoparticles. The subsequent infiltration of nanoparticles adsorbed with the protein into porous microspheres enabled the controlled release of the protein as a function of the amount of infiltrated nanoparticles, since the surface area available on the porous structure is saturated at different levels, thus modifying the protein release rate. Findings were confirmed by both the BET technique (N2 isotherms) and in vitro release studies. During the adsorption process, the pH of the medium plays an important role by creating an environment that favors adsorption between the surfaces of the micro- and nano-structures and the protein. Finally, assays of α-amylase activity using 2-chloro-4-nitrophenyl-α-D-maltotrioside (CNP-G3) as the substrate and the circular dichroism technique confirmed that when this new approach was used no conformational changes were observed in the protein after release. Copyright © 2015 Elsevier B.V. All rights reserved.

Multicolor emission from large-area porous thin films constructed of nanowires of small organic molecules

NASA Astrophysics Data System (ADS)

Wang, Zhe-Chen; Xiao, Wen-Chang; Ding, Xun-Lei; Ma, Yan-Ping; Xue, Wei; He, Sheng-Gui

2008-12-01

We describe a facile low-temperature physical vapor deposition approach to fabricate porous network thin films constructed of nanowires of small organic molecules on a large area. Supermolecular assemblies of pyrene nanowires based on a combination of van der Waals forces and π-π stacking tend to hierarchically self-assemble to form uniform porous films using our techniques. The morphology of the films is studied and we also study several reasons influencing the process of assembly such as evaporation temperature, deposition temperature, and different kinds of substrate. The deposition temperature is determined to be the main reason for hierarchical aggregation. Typically prepared films exhibit unique optical properties, that is, multicolor red-green-blue emissions. This novel method can be applied to other organic molecular systems and may be potentially used to place nanoscaled building blocks directly on solid surfaces for fabricating large-area nanostructure-based flat screens.

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.

Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2/M block in breast cancer cells.

PubMed

Verderio, Paolo; Bonetti, Paolo; Colombo, Miriam; Pandolfi, Laura; Prosperi, Davide

2013-03-11

PLGA nanoparticles are among the most studied polymer nanoformulations for several drugs against different kinds of malignant diseases, thanks to their in vivo stability and tumor localization exploiting the well-documented "enhanced permeation and retention" (EPR) effect. In this paper, we have developed uniform curcumin-bearing PLGA nanoparticles by a single-emulsion process, which exhibited a curcumin release following a Fickian-law diffusion over 10 days in vitro. PLGA nanoparticles were about 120 nm in size, as determined by dynamic light scattering, with a surface negative charge of -30 mV. The loading ratio of encapsulated drug in our PLGA nanoformulation was 8 wt%. PLGA encapsulation provided efficient protection of curcumin from environment, as determined by fluorescence emission experiments. Next, we have investigated the possibility to study the intracellular degradation of nanoparticles associated with a specific G2/M blocking effect on MCF7 breast cancer cells caused by curcumin release in the cytoplasm, which provided direct evidence on the mechanism of action of our nanocomplex. This study was carried out using Annexin V-based cell death analysis, MTT assessment of proliferation, flow cytometry, and confocal laser scanning microscopy. PLGA nanoparticles proved to be completely safe, suggesting a potential utilization of this nanocomplex to improve the intrinsically poor bioavailability of curcumin for the treatment of severe malignant breast cancer.

Synergistic effect of PLGA nanoparticles and submicron triglyceride droplets in enhancing the intestinal solubilisation of a lipophilic weak base.

PubMed

Joyce, Paul; Prestidge, Clive A

2018-06-15

A novel hybrid microparticulate system composed of poly(lactic-co-glycolic) acid (PLGA) nanoparticles and submicron medium-chain triglyceride (MCT) droplets was fabricated to overcome the pH-dependent solubility and precipitation challenges associated with a model poorly water-soluble weak base, cinnarizine (CIN). Molecular CIN was confined within both the lipid and polymer phase of PLGA-lipid hybrid (PLH) and PLGA-lipid-mannitol hybrid (PLMH) particles, which offered significant biopharmaceutical advantages in comparison to the unformulated drug, submicron MCT droplets and PLGA nanoparticles. This was highlighted by a substantial reduction in the pH-induced precipitation during in vitro gastrointestinal two-step dissolution studies. A >2.5-fold solubilisation enhancement was observed for the composite particles during simulated intestinal conditions, compared to pure CIN. Furthermore, the drug solubilisation capacity during in vitro intestinal digesting conditions was ~2-2.5 times greater for PLMH particles compared to the precursor emulsion droplets and PLGA nanoparticles. The observations from this study indicate that a synergy exists between the degradation products of PLGA nanoparticles and lipid droplets, whereby the dual-phase release and dissolution mechanism of the hybrid particles aids in prolonging pH-provoked precipitation. Subsequently, the ability for PLGA polymers and oligomers to act as polymeric precipitation inhibitors has been highlighted for the first time. Copyright © 2018 Elsevier B.V. All rights reserved.

PLGA particulate delivery systems for subunit vaccines: Linking particle properties to immunogenicity.

PubMed

Silva, A L; Soema, P C; Slütter, B; Ossendorp, F; Jiskoot, W

2016-04-02

Among the emerging subunit vaccines are recombinant protein- and synthetic peptide-based vaccine formulations. However, proteins and peptides have a low intrinsic immunogenicity. A common strategy to overcome this is to co-deliver (an) antigen(s) with (an) immune modulator(s) by co-encapsulating them in a particulate delivery system, such as poly(lactic-co-glycolic acid) (PLGA) particles. Particulate PLGA formulations offer many advantages for antigen delivery as they are biocompatible and biodegradable; can protect the antigens from degradation and clearance; allow for co-encapsulation of antigens and immune modulators; can be targeted to antigen presenting cells; and their particulate nature can increase uptake and cross-presentation by mimicking the size and shape of an invading pathogen. In this review we discuss the pros and cons of using PLGA particulate formulations for subunit vaccine delivery and provide an overview of formulation parameters that influence their adjuvanticity and the ensuing immune response.

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

Miscibility of choline-substituted polyphosphazenes with PLGA and osteoblast activity on resulting blends.

PubMed

Weikel, Arlin L; Owens, Steven G; Morozowich, Nicole L; Deng, Meng; Nair, Lakshmi S; Laurencin, Cato T; Allcock, Harry R

2010-11-01

The preparation of phosphazene tissue engineering scaffolds with bioactive side groups has been accomplished using the biological buffer, choline chloride. Mixed-substituent phosphazene cyclic trimers (as model systems) and polymers with choline chloride and glycine ethyl ester, alanine ethyl ester, valine ethyl ester, or phenylalanine ethyl ester were synthesized. Two different synthetic protocols were examined. A sodium hydride mediated route resulted in polyphosphazenes with a low choline content, while a cesium carbonate mediated process produced polyphosphazenes with higher choline content. The phosphazene structures and physical properties were studied using multinuclear NMR, differential scanning calorimetry (DSC), and gel permeation chromatography (GPC) techniques. The resultant polymers were then blended with PLGA (50:50) or PLGA (85:15) and characterized by DSC analysis and scanning electron microscopy (SEM). Polymer products obtained via the sodium hydride route produced miscible blends with both ratios of PLGA, while the cesium carbonate route yielded products with reduced blend miscibility. Heterophase hydrolysis experiments in aqueous media revealed that the polymer blends hydrolyzed to near-neutral pH media (∼5.8 to 6.8). The effect of different molecular structures on cellular adhesion showed osteoblast proliferation with an elevated osteoblast phenotype expression compared to PLGA over a 21-day culture period. Copyright © 2010 Elsevier Ltd. All rights reserved.

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.

'Breath figure' PLGA films as implant coatings for controlled drug release

NASA Astrophysics Data System (ADS)

Ponnusamy, Thiruselvam

The breath figure method is a versatile and facile approach of generating ordered micro and nanoporous structures in polymeric materials. When a polymer solution (dissolved in a high vapor pressure organic solvent) is evaporated out in the presence of a moist air stream, the evaporative cooling effect causes the condensation and nucleation of water droplets onto the polymer solution surface. This leads to the formation of an imprinted porous structure upon removal of the residual solvent and water. The facile removal of the water droplet template leaving its structural imprint is a specifically appealing aspect of the breath figure film technology. The first part of the dissertation work involves the fabrication of drug loaded breath figure thin films and its utilization as a controlled drug release carrier and biomaterial scaffold. In a single fabrication step, single layer/multilayer porous thin films were designed and developed by combining the breath figure process and a modified spin or dip coating technique. Using biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA) and poly (ethylene glycol) (PEG), drug loaded films were fabricated onto FDA approved medical devices (the Glaucoma drainage device and the Surgical hernia mesh). The porosity of the films is in the range of 2-4 microm as characterized by scanning electron microscope. The drug coated medical implants were characterized for their surface and bulk morphology, the degradation rate of the film, drug release rate and cell cytotoxicity. The results suggest that the use of breath figure morphologies in biodegradable polymer films adds an additional level of control to drug release. In comparison to non-porous films, the breath figure films showed an increased degradation and enhanced drug release. Furthermore, the porous nature of the film was investigated as a biomaterial scaffold to construct three dimensional in vitro tissue model systems. The breath figure film with interconnected

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound

PubMed Central

Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

2017-01-01

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA

Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.

PubMed

Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

2017-04-13

In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA

Large-deformation and high-strength amorphous porous carbon nanospheres

NASA Astrophysics Data System (ADS)

Yang, Weizhu; Mao, Shimin; Yang, Jia; Shang, Tao; Song, Hongguang; Mabon, James; Swiech, Wacek; Vance, John R.; Yue, Zhufeng; Dillon, Shen J.; Xu, Hangxun; Xu, Baoxing

2016-04-01

Carbon is one of the most important materials extensively used in industry and our daily life. Crystalline carbon materials such as carbon nanotubes and graphene possess ultrahigh strength and toughness. In contrast, amorphous carbon is known to be very brittle and can sustain little compressive deformation. Inspired by biological shells and honeycomb-like cellular structures in nature, we introduce a class of hybrid structural designs and demonstrate that amorphous porous carbon nanospheres with a thin outer shell can simultaneously achieve high strength and sustain large deformation. The amorphous carbon nanospheres were synthesized via a low-cost, scalable and structure-controllable ultrasonic spray pyrolysis approach using energetic carbon precursors. In situ compression experiments on individual nanospheres show that the amorphous carbon nanospheres with an optimized structure can sustain beyond 50% compressive strain. Both experiments and finite element analyses reveal that the buckling deformation of the outer spherical shell dominates the improvement of strength while the collapse of inner nanoscale pores driven by twisting, rotation, buckling and bending of pore walls contributes to the large deformation.

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.

PLGA nanoparticles for the oral delivery of nuciferine: preparation, physicochemical characterization and in vitro/in vivo studies.

PubMed

Liu, Ying; Wu, Xin; Mi, Yushuai; Zhang, Bimeng; Gu, Shengying; Liu, Gaolin; Li, Xiaoyu

2017-11-01

This article reports a promising approach to enhance the oral delivery of nuciferine (NUC), improve its aqueous solubility and bioavailability, and allow its controlled release as well as inhibiting lipid accumulation. NUC-loaded poly lactic-co-glycolic acid nanoparticles (NUC-PLGA-NPs) were prepared according to a solid/oil/water (s/o/w) emulsion technique due to the water-insolubility of NUC. PLGA exhibited excellent loading capacity for NUC with adjustable dosing ratios. The drug loading and encapsulation efficiency of optimized formulation were 8.89 ± 0.71 and 88.54 ± 7.08%, respectively. NUC-PLGA-NPs exhibited a spherical morphology with average size of 150.83 ± 5.72 nm and negative charge of -22.73 ± 1.63 mV, which are suitable for oral administration. A sustained NUC released from NUC-PLGA-NPs with an initial exponential release owing to the surface associated drug followed by a slower release of NUC, which was entrapped in the core. In addition, ∼77 ± 6.67% was released in simulating intestinal juice, while only about 45.95 ± 5.2% in simulating gastric juice. NUC-PLGA-NPs are more efficient against oleic acid (OA)-induced hepatic steatosis in HepG 2 cells when compared to naked NUC (n-NUC, *p < 0.05). The oral bioavailability of NUC-PLGA-NPs group was significantly higher (**p < 0.01) and a significantly decreased serum levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), as well as a higher concentration of high-density lipoprotein cholesterol (HDL-C) was observed, compared with that of n-NUC treated group. These findings suggest that NUC-PLGA-NPs hold great promise for sustained and controlled drug delivery with improved bioavailability to alleviating lipogenesis.

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

PubMed

Gidwani, Bina; Vyas, Amber

2016-03-01

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

A "room-temperature" injection molding/particulate leaching approach for fabrication of biodegradable three-dimensional porous scaffolds.

PubMed

Wu, Linbo; Jing, Dianying; Ding, Jiandong

2006-01-01

A "room-temperature" injection molding approach combined with particulate leaching (RTIM/PL) has been, for the first time, developed in this work to fabricate three-dimensional porous scaffolds composed of biodegradable polyesters for tissue engineering. In this approach, a "wet" composite of particulate/polymer/solvent was used in processing, and thus the injection was not performed at melting state. Appropriate viscosity and flowability were facilely obtained at a certain solvent content so that the composite was able to be injected into a mould under low pressure at room temperature, which was very beneficial for avoiding thermal degradation of polyesters. As a demonstration, tubular and ear-shaped porous scaffolds were fabricated from biodegradable poly(D,L-lactide-co-glycolide) (PLGA) by this technology. Porosities of the resulting scaffolds were as high as 94%. The pores were well interconnected. Besides the well-known characteristics of injection molding to be suitable for automatization of a fabrication process with high repeatability and precision, this RTIM/PL approach is much suitable for tailoring highly porous foams with its advantages flexible for shaping complicated scaffolds, free of thermal degradation and high-pressure machine, etc.

Paclitaxel-loaded PLGA nanoparticles surface modified with transferrin and Pluronic((R))P85, an in vitro cell line and in vivo biodistribution studies on rat model.

PubMed

Shah, Neha; Chaudhari, Kiran; Dantuluri, Prudhviraju; Murthy, R S R; Das, Susobhan

2009-08-01

The development of multidrug resistance (due to drug efflux by P-glycoproteins) is a major drawback with the use of paclitaxel (PTX) in the treatment of cancer. The rationale behind this study is to prepare PTX nanoparticles (NPs) for the reversal of multidrug resistance based on the fact that PTX loaded into NPs is not recognized by P-glycoproteins and hence is not effluxed out of the cell. Also, the intracellular penetration of the NPs could be enhanced by anchoring transferrin (Tf) on the PTX-PLGA-NPs. PTX-loaded PLGA NPs (PTX-PLGA-NPs), Pluronic((R))P85-coated PLGA NPs (P85-PTX-PLGA-NPs), and Tf-anchored PLGA NPs (Tf-PTX-PLGA-NPs) were prepared and evaluted for cytotoxicity and intracellular uptake using C6 rat glioma cell line. A significant increase in cytotoxicity was observed in the order of Tf-PTX-PLGA-NPs > P85-PTX-PLGA-NPs > PTX-PLGA-NPs in comparison to drug solution. In vivo biodistribution on male Sprague-Dawley rats bearing C6 glioma (subcutaneous) showed higher tumor PTX concentrations in animals administered with PTX-NPs compared to drug solution.

PEG-lipid-PLGA hybrid nanoparticles loaded with berberine-phospholipid complex to facilitate the oral delivery efficiency.

PubMed

Yu, Fei; Ao, Mingtao; Zheng, Xiao; Li, Nini; Xia, Junjie; Li, Yang; Li, Donghui; Hou, Zhenqing; Qi, Zhongquan; Chen, Xiao Dong

2017-11-01

The natural product berberine (BBR), present in various plants, arouses great interests because of its numerous pharmacological effects. However, the further development and application of BBR had been hampered by its poor oral bioavailability. In this work, we report on polymer-lipid hybrid nanoparticles (PEG-lipid-PLGA NPs) loaded with BBR phospholipid complex using a solvent evaporation method for enhancing the oral BBR efficiency. The advantage of this new drug delivery system is that the BBR-soybean phosphatidylcholine complex (BBR-SPC) could be used to enhance the liposolubility of BBR and improve the affinity with the biodegradable polymer to increase the drug-loading capacity and controlled/sustained release. The entrapment efficiency of the PEG-lipid-PLGA NPs/BBR-SPC was observed to approach approximately 89% which is more than 2.4 times compared with that of the PEG-lipid-PLGA NPs/BBR. To the best of our knowledge, this is the first report on using polymer material for effective encapsulation of BBR to improve its oral bioavailability. The prepared BBR delivery systems demonstrated a uniform spherical shape, a well-dispersed core-shell structure and a small particle size (149.6 ± 5.1 nm). The crystallographic and thermal analysis has indicated that the BBR dispersed in the PEG-lipid-PLGA NPs matrix is in an amorphous form. More importantly, the enhancement in the oral relative bioavailability of the PEG-lipid-PLGA NPs/BBR-SPC was ∼343% compared with that of BBR. These positive results demonstrated that PEG-lipid-PLGA NPs/BBR-SPC may have the potential for facilitating the oral drug delivery of BBR.

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.

Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release.

PubMed

Chhabra, Resham; Grabrucker, Andreas M; Veratti, Patrizia; Belletti, Daniela; Boeckers, Tobias M; Vandelli, Maria Angela; Forni, Flavio; Tosi, Giovanni; Ruozi, Barbara

2014-08-25

Polymeric nanoparticles (NPs) offer a promising approach for therapeutic intracellular delivery of proteins, conventionally hampered by short half-lives, instability and immunogenicity. Remarkably, NPs uptake occurs via endocytic internalization leading to NPs content's release within lysosomes. To overcome lysosomal degradation and achieve NPs and/or loaded proteins release into cytosol, we propose the formulation of hybrid NPs by adding 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as pH sensitive component in the formulation of poly-lactide-co-glycolide (PLGA) NPs. Hybrid NPs, featured by different DOPE/PLGA ratios, were characterized in terms of structure, stability and lipid organization within the polymeric matrix. Experiments on NIH cells and rat primary neuronal cultures highlighted the safety profile of hybrid NPs. Moreover, after internalization, NPs are able to transiently destabilize the integrity of lysosomes in which they are taken up, speeding their escape and favoring cytoplasmatic localization. Thus, these DOPE/PLGA-NPs configure themselves as promising carriers for intracellular protein delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

The effects of quercetin-loaded PLGA-TPGS nanoparticles on ultraviolet B-induced skin damages in vivo.

PubMed

Zhu, Xianbing; Zeng, Xiaowei; Zhang, Xudong; Cao, Wei; Wang, Yilin; Chen, Houjie; Wang, Teng; Tsai, Hsiang-I; Zhang, Ran; Chang, Danfeng; He, Shuai; Mei, Lin; Shi, Xiaojun

2016-04-01

Ultraviolet (UV) radiation has deleterious effects on living organisms, and functions as a tumor initiator and promoter. Multiple natural compounds, like quercetin, have been shown the protective effects on UV-induced damage. However, quercetin is extremely hydrophobic and limited by its poor percutaneous permeation and skin deposition. Here, we show that quercetin-loaded PLGA-TPGS nanoparticles could overcome low hydrophilicity of quercetin and improve its anti-UVB effect. Quercetin-loaded NPs can significantly block UVB irradiation induced COX-2 up-expression and NF-kB activation in Hacat cell line. Moreover, PLGA-TPGS NPs could efficiently get through epidermis and reach dermis. Treatment of mice with quercetin-loaded NPs also attenuates UVB irradiation-associated macroscopic and histopathological changes in mice skin. These results demonstrated that copolymer PLGA-TPGS could be used as drug nanocarriers against skin damage and disease. The findings provide an external use of PLGA-TPGS nanocarriers for application in the treatment of skin diseases. Skin is the largest organ in the body and is subjected to ultraviolet (UV) radiation damage daily from the sun. Excessive exposure has been linked to the development of skin cancer. Hence, topically applied agents can play a major role in skin protection. In this article, the authors developed quercetin-loaded PLGA-TPGS nanoparticles and showed their anti-UVB effect. Copyright © 2015 Elsevier Inc. All rights reserved.

Computational Intelligence Modeling of the Macromolecules Release from PLGA Microspheres-Focus on Feature Selection.

PubMed

Zawbaa, Hossam M; Szlȩk, Jakub; Grosan, Crina; Jachowicz, Renata; Mendyk, Aleksander

2016-01-01

Poly-lactide-co-glycolide (PLGA) is a copolymer of lactic and glycolic acid. Drug release from PLGA microspheres depends not only on polymer properties but also on drug type, particle size, morphology of microspheres, release conditions, etc. Selecting a subset of relevant properties for PLGA is a challenging machine learning task as there are over three hundred features to consider. In this work, we formulate the selection of critical attributes for PLGA as a multiobjective optimization problem with the aim of minimizing the error of predicting the dissolution profile while reducing the number of attributes selected. Four bio-inspired optimization algorithms: antlion optimization, binary version of antlion optimization, grey wolf optimization, and social spider optimization are used to select the optimal feature set for predicting the dissolution profile of PLGA. Besides these, LASSO algorithm is also used for comparisons. Selection of crucial variables is performed under the assumption that both predictability and model simplicity are of equal importance to the final result. During the feature selection process, a set of input variables is employed to find minimum generalization error across different predictive models and their settings/architectures. The methodology is evaluated using predictive modeling for which various tools are chosen, such as Cubist, random forests, artificial neural networks (monotonic MLP, deep learning MLP), multivariate adaptive regression splines, classification and regression tree, and hybrid systems of fuzzy logic and evolutionary computations (fugeR). The experimental results are compared with the results reported by Szlȩk. We obtain a normalized root mean square error (NRMSE) of 15.97% versus 15.4%, and the number of selected input features is smaller, nine versus eleven.

Computational Intelligence Modeling of the Macromolecules Release from PLGA Microspheres—Focus on Feature Selection

PubMed Central

Zawbaa, Hossam M.; Szlȩk, Jakub; Grosan, Crina; Jachowicz, Renata; Mendyk, Aleksander

2016-01-01

Poly-lactide-co-glycolide (PLGA) is a copolymer of lactic and glycolic acid. Drug release from PLGA microspheres depends not only on polymer properties but also on drug type, particle size, morphology of microspheres, release conditions, etc. Selecting a subset of relevant properties for PLGA is a challenging machine learning task as there are over three hundred features to consider. In this work, we formulate the selection of critical attributes for PLGA as a multiobjective optimization problem with the aim of minimizing the error of predicting the dissolution profile while reducing the number of attributes selected. Four bio-inspired optimization algorithms: antlion optimization, binary version of antlion optimization, grey wolf optimization, and social spider optimization are used to select the optimal feature set for predicting the dissolution profile of PLGA. Besides these, LASSO algorithm is also used for comparisons. Selection of crucial variables is performed under the assumption that both predictability and model simplicity are of equal importance to the final result. During the feature selection process, a set of input variables is employed to find minimum generalization error across different predictive models and their settings/architectures. The methodology is evaluated using predictive modeling for which various tools are chosen, such as Cubist, random forests, artificial neural networks (monotonic MLP, deep learning MLP), multivariate adaptive regression splines, classification and regression tree, and hybrid systems of fuzzy logic and evolutionary computations (fugeR). The experimental results are compared with the results reported by Szlȩk. We obtain a normalized root mean square error (NRMSE) of 15.97% versus 15.4%, and the number of selected input features is smaller, nine versus eleven. PMID:27315205

Graphene oxide-stimulated myogenic differentiation of C2C12 cells on PLGA/RGD peptide nanofiber matrices

NASA Astrophysics Data System (ADS)

Shin, Y. C.; Lee, J. H.; Kim, M. J.; Hong, S. W.; Oh, J.-W.; Kim, C.-S.; Kim, B.; Hyun, J. K.; Kim, Y.-J.; Han, D.-W.

2015-07-01

During the last decade, much attention has been paid to graphene-based nanomaterials because they are considered as potential candidates for biomedical applications such as scaffolds for tissue engineering and substrates for the differentiation of stem cells. Until now, electrospun matrices composed of various biodegradable copolymers have been extensively developed for tissue engineering and regeneration; however, their use in combination with graphene oxide (GO) is novel and challenging. In this study, nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 phage with RGD peptide displayed on its surface (RGD peptide-M13 phage) were prepared as extracellular matrix (ECM)-mimicking substrates. RGD peptide is a tripeptide (Arg-Gly-Asp) found on ECM proteins that promotes various cellular behaviors. The physicochemical properties of PLGA and RGD peptide-M13 phage (PLGA/RGD peptide) nanofiber matrices were characterized by atomic force microscopy, Fourier-transform infrared spectroscopy and thermogravimetric analysis. In addition, the growth of C2C12 mouse myoblasts on the PLGA/RGD peptide matrices was examined by measuring the metabolic activity. Moreover, the differentiation of C2C12 mouse myoblasts on the matrices when treated with GO was evaluated. The cellular behaviors, including growth and differentiation of C2C12 mouse myoblasts, were substantially enhanced on the PLGA/RGD peptide nanofiber matrices when treated with GO. Overall, these findings suggest that the PLGA/RGD peptide nanofiber matrices can be used in combination with GO as a novel strategy for skeletal tissue regeneration.

Electrospraying technique for the fabrication of metronidazole contained PLGA particles and their release profile.

PubMed

Prabhakaran, Molamma P; Zamani, Maedeh; Felice, Betiana; Ramakrishna, Seeram

2015-11-01

Advanced engineering of materials for the development of drug delivery devices provides scope for novel and versatile strategies for treatment of various diseases. 'Electrospraying' was used to prepare PLGA microparticles and further encapsulate the drug, metronidazole (Met) within the particles to function as a drug delivery system. Two different solvents were utilized for the preparation of drug loaded PLGA particles, whereby the polymeric solution in dichloromethane (DCM) produced particles of bigger sizes than using trifluoroethanol (TFE). Scanning electron microscopy showed the spherical morphology of the particles, with sizes of 3946±407nm and 1774±167nm, respectively for PLGA-Met(DCM) and PLGA-Met(TFE). The FTIR spectroscopy proved the incorporation of metronidazole in the polymer, but without any specific drug-polymer interaction. The release of the drug from the particles was studied in phosphate buffered saline, where a sustained drug release was obtained for at least 41days. Cytotoxicity evaluation of the drug extract using mesenchymal stem cells (MSCs) showed not hindering the proliferation of MSCs, and the cell phenotype was retained after incubation in the drug containing media. Electrospraying is suggested as a cost-effective and single step process for the preparation of polymeric microparticles for prolonged and controlled release of drug. Copyright © 2015 Elsevier B.V. All rights reserved.

Chlamydia trachomatis recombinant MOMP encapsulated in PLGA nanoparticles triggers primarily T helper 1 cellular and antibody immune responses in mice: a desirable candidate nanovaccine.

PubMed

Fairley, Stacie J; Singh, Shree R; Yilma, Abebayehu N; Waffo, Alain B; Subbarayan, Praseetha; Dixit, Saurabh; Taha, Murtada A; Cambridge, Chino D; Dennis, Vida A

2013-01-01

We recently demonstrated by in vitro experiments that PLGA (poly D, L-lactide-co-glycolide) potentiates T helper 1 (Th1) immune responses induced by a peptide derived from the recombinant major outer membrane protein (rMOMP) of Chlamydia trachomatis, and may be a promising vaccine delivery system. Herein we evaluated the immune-potentiating potential of PLGA by encapsulating the full-length rMOMP (PLGA-rMOMP), characterizing it in vitro, and investigating its immunogenicity in vivo. Our hypothesis was that PLGA-rMOMP triggers Th1 immune responses in mice, which are desirable prerequisites for a C. trachomatis candidate nanovaccine. Physical-structural characterizations of PLGA-rMOMP revealed its size (approximately 272 nm), zeta potential (-14.30 mV), apparent spherical smooth morphology, and continuous slow release pattern. PLGA potentiated the ability of encapsulated rMOMP to trigger production of cytokines and chemokines by mouse J774 macrophages. Flow cytometric analyses revealed that spleen cells from BALB/c mice immunized with PLGA-rMOMP had elevated numbers of CD4+ and CD8+ T cell subsets, and secreted more rMOMP-specific interferon-gamma (Th1) and interleukin (IL)-12p40 (Th1/Th17) than IL-4 and IL-10 (Th2) cytokines. PLGA-rMOMP-immunized mice produced higher serum immunoglobulin (Ig)G and IgG2a (Th1) than IgG1 (Th2) rMOMP-specific antibodies. Notably, sera from PLGA-rMOMP-immunized mice had a 64-fold higher Th1 than Th2 antibody titer, whereas mice immunized with rMOMP in Freund's adjuvant had only a four-fold higher Th1 than Th2 antibody titer, suggesting primarily induction of a Th1 antibody response in PLGA-rMOMP-immunized mice. Our data underscore PLGA as an effective delivery system for a C. trachomatis vaccine. The capacity of PLGA-rMOMP to trigger primarily Th1 immune responses in mice promotes it as a highly desirable candidate nanovaccine against C. trachomatis.

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. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Cell Attachment and Proliferation of Human Adipose-Derived Stem Cells on PLGA/Chitosan Electrospun Nano-Biocomposite.

PubMed

Razavi, Shahnaz; Karbasi, Saeed; Morshed, Mohammad; Zarkesh Esfahani, Hamid; Golozar, Mohammad; Vaezifar, Sedigheh

2015-01-01

In this study, nano-biocomposite composed of poly (lactide-co-glycolide) (PLGA) and chitosan (CS) were electrospun through a single nozzle by dispersing the CS nano-powders in PLGA solution. The cellular behavior of human adipose derived stem cells (h-ADSCs) on random and aligned scaffolds was then evaluated. In this experimental study, the PLGA/CS scaffolds were prepared at the different ratios of 90/10, 80/20, and 70/30 (w/w) %. Morphology, cell adhesion and prolif- eration rate of h-ADSCs on the scaffolds were assessed using scanning electron microscope (SEM), 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and trypan blue staining respectively. H-ADSCs seeded on the matrices indicated that the PLGA/CS composite matrix with aligned nanofibres and higher content of CS nano-powders gave significantly better performance than others in terms of cell adhesion and proliferation rate (P<0.05). We found that CS enhanced cell adhesion and proliferation rate, and aligned nanofibers guided cell growth along the longitudinal axis of the nanofibers, which would provide a beneficial approach for tissue engineering.

Target-specific cellular uptake of PLGA nanoparticles coated with poly(L-lysine)-poly(ethylene glycol)-folate conjugate.

PubMed

Kim, Sun Hwa; Jeong, Ji Hoon; Chun, Ki Woo; Park, Tae Gwan

2005-09-13

Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with anionic surface charge were surface coated with cationic di-block copolymer, poly(L-lysine)-poly(ethylene glycol)-folate (PLL-PEG-FOL) conjugate, for enhancing their site-specific intracellular delivery against folate receptor overexpressing cancer cells. The PLGA nanoparticles coated with the conjugate were characterized in terms of size, surface charge, and change in surface composition by XPS. By employing the flow cytometry method and confocal image analysis, the extent of cellular uptake was comparatively evaluated under various conditions. PLL-PEG-FOL coated PLGA nanoparticles demonstrated far greater extent of cellular uptake to KB cells, suggesting that they were mainly taken up by folate receptor-mediated endocytosis. The enhanced cellular uptake was also observed even in the presence of serum proteins, possibly due to the densely seeded PEG chains. The PLL-PEG-FOL coated PLGA nanoparticles could be potentially applied for cancer cell targeted delivery of various therapeutic agents.

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

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method.

PubMed

Kashi, Tahereh Sadat Jafarzadeh; Eskandarion, Solmaz; Esfandyari-Manesh, Mehdi; Marashi, Seyyed Mahmoud Amin; Samadi, Nasrin; Fatemi, Seyyed Mostafa; Atyabi, Fatemeh; Eshraghi, Saeed; Dinarvand, Rassoul

2012-01-01

Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. The nanoparticles prepared in this study were spherical, with an average particle size of 85-424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug.

Vitamin E-Oligo(methyl diglycol l-glutamate) as a Biocompatible and Functional Surfactant for Facile Preparation of Active Tumor-Targeting PLGA Nanoparticles.

PubMed

Wu, Jintian; Zhang, Jian; Deng, Chao; Meng, Fenghua; Zhong, Zhiyuan

2016-07-11

Poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles have attracted an enormous interest for controlled drug delivery. Their clinical applications are, however, partly hindered by lack of biocompatible, biodegradable and functional surfactants. Here, we designed and developed a novel biocompatible surfactant based on amphiphilic vitamin E-oligo(methyl diglycol l-glutamate) (VEOEG) for facile fabrication of robust and tumor-targeting PLGA-based nanomedicines. VEOEG was prepared with controlled Mn of 1.7-2.6 kg/mol and low molecular weight distribution (Đ = 1.04-1.16) via polymerization of methyl diglycol l-glutamate N-carboxyanhydride using vitamin E-ethylenediamine derivative (VE-NH2) as an initiator. VEOEG had a hydrophile-lipophile balance data of 13.8-16.1 and critical micellar concentration of 189.3-203.8 mg/L depending on lengths of oligopeptide. Using VEOEG as a surfactant, PLGA nanoparticles could be obtained via nanoprecipitation method with a small and uniform hydrodynamic size of 135 nm and positive surface charge of +26.6 mV, in accordance with presence of amino groups at the surface. The resulting PLGA nanoparticles could be readily coated with hyaluronic acid (HA) to form highly stable, small-sized (143 nm), monodisperse, and negatively charged nanoparticles (HA-PLGA NPs). Notably, paclitaxel-loaded HA-PLGA NPs (PTX-HA-PLGA NPs) exhibited better antitumor effects in CD44-positive MCF-7 breast tumor cells than Taxol (a clinical paclitaxel formulation). The in vivo pharmacokinetics assay in nude mice displayed that PTX-HA-PLGA NPs possessed a long plasma half-life of 3.14 h. The in vivo biodistribution studies revealed that PTX-HA-PLGA NPs had a high tumor PTX level of 8.4% ID/g, about 6 times better than that of Taxol. Interestingly, therapeutic studies showed that PTX-HA-PLGA NPs caused significantly more effective tumor growth inhibition, better survival rate and lower adverse effect than Taxol. VEOEG has emerged as a versatile and functional

Hyaluronic acid-grafted PLGA nanoparticles for the sustained delivery of berberine chloride for an efficient suppression of Ehrlich ascites tumors.

PubMed

Bhatnagar, Priyanka; Kumari, Manisha; Pahuja, Richa; Pant, A B; Shukla, Y; Kumar, Pradeep; Gupta, K C

2018-06-01

To promote the specific targeting and elimination of CD44-positive cancer cells, berberine chloride (BRB)-encapsulated hyaluronic acid-grafted poly(lactic-co-glycolic acid) copolymer (BRB-d(HA)-g-PLGA) nanoparticles (NPs) were prepared. The targeted action of these NPs was compared to non-targeted BRB-loaded PLGA NPs and bulk BRB. The in vitro studies demonstrated faster release of BRB and increased cytotoxicity of BRB-d(HA)-g-PLGA NPs in Hela and MCF-7 cells in comparison to BRB-PLGA NPs and bulk BRB. The uptake of BRB-d(HA)-g-PLGA NPs was increased in case of MCF-7 cells as compared to HeLa cells owing to the higher expression of CD44 receptors on MCF-7 cells. The CD44 receptor-mediated uptake of these NPs was confirmed through competitive inhibition experiments. The in vitro results were further validated in vivo in Ehrlich Ascites Carcinoma (EAC)-bearing mice. EAC-bearing mice were injected intravenously with these NPs and the results obtained were compared with that of BRB-PLGA NPs and bulk BRB. BRB-d(HA)-g-PLGA NPs were found to significantly enhance apoptosis, sub-G1 content, life span, mean survival time, and ROS levels in EAC cells with subsequent decrease in mitochondrial membrane potential and tumor burden ion tumor-bearing mice. Taking into account the findings of in vitro and in vivo studies, the enhanced and targeted anti-tumor activity of HA-grafted PLGA copolymer-encapsulated NPs of BRB cannot be negated. Therefore, HA-grafted nanoparticle-based delivery of BRB may offer a promising and improved alternative for anti-tumor therapy.

Preparation and characterization of teniposide PLGA nanoparticles and their uptake in human glioblastoma U87MG cells.

PubMed

Mo, Liqian; Hou, Lianbing; Guo, Dan; Xiao, Xiaoyan; Mao, Ping; Yang, Xixiao

2012-10-15

Many studies have demonstrated the uptake mechanisms of various nanoparticle delivery systems with different physicochemical properties in different cells. In this study, we report for the first time the preparation and characterization of teniposide (VM-26) poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) and their cellular uptake pathways in human glioblastoma U87MG cells. The nanoparticles prepared with oil-in-water (O/W) single-emulsion solvent evaporation method had a small particle size and spherical shape and provided effective protection against degradation of teniposide in PBS solution. Differential scanning calorimeter (DSC) thermograms concluded that VM-26 was dispersed as amorphous or disordered crystalline phase in the PLGA matrix. A cytotoxicity study revealed that, in a 24h period, blank PLGA NPs had no cytotoxicity, whereas teniposide-loaded PLGA NPs (VM-26-NPs) had U87MG cytotoxicity levels similar to free teniposide. Confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM) images showed the distribution and degradation processes of nanoparticles in cells. An endocytosis inhibition test indicated that clathrin-mediated endocytosis and macropinocytosis were the primary modes of engulfment involved in the internalization of VM-26-NPs. Our findings suggest that PLGA nanoparticles containing a sustained release formula of teniposide may multiplex the therapeutic effect and ultimately degrade in lysosomal within human glioblastoma U87MG cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Injectable Shear-Thinning CaSO4/FGF-18-Incorporated Chitin-PLGA Hydrogel Enhances Bone Regeneration in Mice Cranial Bone Defect Model.

PubMed

Sivashanmugam, A; Charoenlarp, Pornkawee; Deepthi, S; Rajendran, Arunkumar; Nair, Shantikumar V; Iseki, Sachiko; Jayakumar, R

2017-12-13

For craniofacial bone regeneration, shear-thinning injectable hydrogels are favored over conventional scaffolds because of their improved defect margin adaptability, easier handling, and ability to be injected manually into deeper tissues. The most accepted method, after autografting, is the use of recombinant human bone morphogenetic protein-2 (BMP-2); however, complications such as interindividual variations, edema, and poor cost-efficiency in supraphysiological doses have been reported. The endogenous synthesis of BMP-2 is desirable, and a molecule which induces this is fibroblast growth factor-18 (FGF-18) because it can upregulate the BMP-2 expression  by supressing noggin. We developed a chitin-poly(lactide-co-glycolide) (PLGA) composite hydrogel by regeneration chemistry and then incorporated CaSO 4 and FGF-18 for this purpose. Rheologically, a 7-fold increase in the elastic modulus was observed in the CaSO 4 -incorporated chitin-PLGA hydrogels as compared to the chitin-PLGA hydrogel. Shear-thinning Herschel-Bulkley fluid nature was observed for both hydrogels. Chitin-PLGA/CaSO 4 gel showed sustained release of FGF-18. In vitro osteogenic differentiation showed an enhanced alkaline phosphatase (ALP) expression in the FGF-18-containing chitin-PLGA/CaSO 4 gel when compared to cells alone. Further, it was confirmed by studying the expression of osteogenic genes [RUNX2, ALP, BMP-2, osteocalcin (OCN), and osteopontin (OPN)], immunofluorescence staining of BMP-2, OCN, and OPN, and alizarin red S staining. Incorporation of FGF-18 in the hydrogel increased the endothelial cell migration. Further, the regeneration potential of the prepared hydrogels was tested in vivo, and longitudinal live animal μ-CT was performed. FGF-18-loaded chitin-PLGA/CaSO 4 showed early and almost complete bone healing in comparison with chitin-PLGA/CaSO 4 , chitin-PLGA/FGF-18, chitin-PLGA, and sham control systems, as confirmed by hematoxylin and eosin and osteoid tetrachrome stainings

Porous medium convection at large Rayleigh number: Studies of coherent structure, transport, and reduced dynamics

NASA Astrophysics Data System (ADS)

Wen, Baole

Buoyancy-driven convection in fluid-saturated porous media is a key environmental and technological process, with applications ranging from carbon dioxide storage in terrestrial aquifers to the design of compact heat exchangers. Porous medium convection is also a paradigm for forced-dissipative infinite-dimensional dynamical systems, exhibiting spatiotemporally chaotic dynamics if not "true" turbulence. The objective of this dissertation research is to quantitatively characterize the dynamics and heat transport in two-dimensional horizontal and inclined porous medium convection between isothermal plane parallel boundaries at asymptotically large values of the Rayleigh number Ra by investigating the emergent, quasi-coherent flow. This investigation employs a complement of direct numerical simulations (DNS), secondary stability and dynamical systems theory, and variational analysis. The DNS confirm the remarkable tendency for the interior flow to self-organize into closely-spaced columnar plumes at sufficiently large Ra (up to Ra ≃ 105), with more complex spatiotemporal features being confined to boundary layers near the heated and cooled walls. The relatively simple form of the interior flow motivates investigation of unstable steady and time-periodic convective states at large Ra as a function of the domain aspect ratio L. To gain insight into the development of spatiotemporally chaotic convection, the (secondary) stability of these fully nonlinear states to small-amplitude disturbances is investigated using a spatial Floquet analysis. The results indicate that there exist two distinct modes of instability at large Ra: a bulk instability mode and a wall instability mode. The former usually is excited by long-wavelength disturbances and is generally much weaker than the latter. DNS, strategically initialized to investigate the fully nonlinear evolution of the most dangerous secondary instability modes, suggest that the (long time) mean inter-plume spacing in

Preparation, Optimization and Toxicity Evaluation of (SPION-PLGA) ±PEG Nanoparticles Loaded with Gemcitabine as a Multifunctional Nanoparticle for Therapeutic and Diagnostic Applications.

PubMed

Hamzian, Nima; Hashemi, Maryam; Ghorbani, Mahdi; Bahreyni Toosi, Mohammad Hossein; Ramezani, Mohammad

2017-01-01

The aim of this study was to develop a novel multifunctional nanoparticle, which encapsulates SPION and Gemcitabine in PLGA ± PEG to form multifunctional drug delivery system. For this aim, super paramagnetic iron oxide nanoparticles (SPIONs) were simultaneously synthesized and encapsulated with Gemcitabine (Gem) in PLGA ± PEG copolymers via W/O/W double emulsification method. Optimum size and encapsulation efficiency for radiosensitization, hyperthermia and diagnostic applications were considered and the preparation parameters systematically were investigated and physicochemical characteristics of optimized nanoparticle were studied. Then SPION-PLGA and PLGA-Gem nanoparticles were prepared with the same optimized parameters and the toxicity of these nanoparticles was compared with Gemcitabine in human breast cancer cell line (MCF-7). The optimum preparation parameters were obtained with Gem/polymer equal to 0.04, SPION/polymer equal to 0.8 and 1% sucrose per 20 mg of polymer. The hydrodynamic diameters of all nanoparticles were under 200 nm. Encapsulation efficiency was adjusted between 13.2% to 16.1% for Gemcitabine and 48.2% to 50.1% for SPION. In-vitro Gemcitabine release kinetics had controlled behavior. Enhancement ratios for PLGA-Gem and SPION-PLGA-Gem at concentration of nanoparticles equal to IC50 of Gemcitabine were 1.53 and 1.89 respectively. The statistical difference was significant ( p -value = 0.006 for SPION-PLGA-Gem and p -value = 0.015 for PLGA-Gem compared with Gemcitabine). In conclusion, we have successfully developed a Gemcitabine loaded super paramagnetic PLGA-Iron Oxide multifunctional drag delivery system. Future work includes in-vitro and in-vivo investigation of radiosensitization and other application of these nanoparticles.

Quantitative Assessment of Antimicrobial Activity of PLGA Films Loaded with 4-Hexylresorcinol

PubMed Central

Kemme, Michael; Heinzel-Wieland, Regina

2018-01-01

Profound screening and evaluation methods for biocide-releasing polymer films are crucial for predicting applicability and therapeutic outcome of these drug delivery systems. For this purpose, we developed an agar overlay assay embedding biopolymer composite films in a seeded microbial lawn. By combining this approach with model-dependent analysis for agar diffusion, antimicrobial potency of the entrapped drug can be calculated in terms of minimum inhibitory concentrations (MICs). Thus, the topical antiseptic 4-hexylresorcinol (4-HR) was incorporated into poly(lactic-co-glycolic acid) (PLGA) films at different loadings up to 3.7 mg/cm2 surface area through a solvent casting technique. The antimicrobial activity of 4-HR released from these composite films was assessed against a panel of Gram-negative and Gram–positive bacteria, yeasts and filamentous fungi by the proposed assay. All the microbial strains tested were susceptible to PLGA-4-HR films with MIC values down to 0.4% (w/w). The presented approach serves as a reliable method in screening and quantifying the antimicrobial activity of polymer composite films. Moreover, 4-HR-loaded PLGA films are a promising biomaterial that may find future application in the biomedical and packaging sector. PMID:29324696

Study of Antimicrobial Effects of Clarithromycin Loaded PLGA Nanoparticles against Clinical Strains of Helicobacter pylori.

PubMed

Lotfipour, F; Valizadeh, H; Milani, M; Bahrami, N; Ghotaslou, R

2016-01-01

Clarithromycin (CLR) formulation was prepared as PLGA nanoparticles in order to enhance the therapeutic effects using the distinctive features of a nanoparticulate delivery system. CLR loaded PLGA nanoparticles were prepared by Quasi Emulsion Solvent Diffusion (QESD) method using Poly lactic-co-Glycolic Acid (PLGA) as a biodegradable polymer. Antibacterial activity of the prepared formulations was evaluated against clinical strains of Helicobacter pylori, isolated from gastric biopsies of patients with gastritis, duodenal ulcer, peptic ulcer, and gastroesophageal reflux disease undergoing endoscopy, by using agar dilution method.Spherical nanoparticles with relatively narrow size distribution (between 200 and 800 nm) in the size range of 305 ± 138, 344 ± 148 and 362 ± 110 nm were achieved for F22, F23 and F23 respectively. CLR encapsulation percentages were measured to be 57.4 ± 4.3 to 80.2 ± 4.0%. CLR loaded PLGA nanoparticles showed equal or enhanced eradication effect against H. pylori strains according to the declined MIC values in comparison with the untreated CLR.In conclusion, the prepared CLR nanoformulation showed appropriate physicochemical properties and improved activity against H. pylori that could be a suitable candidate for oral preparations. © Georg Thieme Verlag KG Stuttgart · New York.

High-throughput screening of PLGA thin films utilizing hydrophobic fluorescent dyes for hydrophobic drug compounds.

PubMed

Steele, Terry W J; Huang, Charlotte L; Kumar, Saranya; Widjaja, Effendi; Chiang Boey, Freddy Yin; Loo, Joachim S C; Venkatraman, Subbu S

2011-10-01

Hydrophobic, antirestenotic drugs such as paclitaxel (PCTX) and rapamycin are often incorporated into thin film coatings for local delivery using implantable medical devices and polymers such as drug-eluting stents and balloons. Selecting the optimum coating formulation through screening the release profile of these drugs in thin films is time consuming and labor intensive. We describe here a high-throughput assay utilizing three model hydrophobic fluorescent compounds: fluorescein diacetate (FDAc), coumarin-6, and rhodamine 6G that were incorporated into poly(d,l-lactide-co-glycolide) (PLGA) and PLGA-polyethylene glycol films. Raman microscopy determined the hydrophobic fluorescent dye distribution within the PLGA thin films in comparison with that of PCTX. Their subsequent release was screened in a high-throughput assay and directly compared with HPLC quantification of PCTX release. It was observed that PCTX controlled-release kinetics could be mimicked by a hydrophobic dye that had similar octanol-water partition coefficient values and homogeneous dissolution in a PLGA matrix as the drug. In particular, FDAc was found to be the optimal hydrophobic dye at modeling the burst release as well as the total amount of PCTX released over a period of 30 days. Copyright © 2011 Wiley-Liss, Inc.

Curcumin Loaded-PLGA Nanoparticles Conjugated with Tet-1 Peptide for Potential Use in Alzheimer's Disease

PubMed Central

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. PMID:22403681

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

PubMed

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

2017-08-07

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

Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method

PubMed Central

Kashi, Tahereh Sadat Jafarzadeh; Eskandarion, Solmaz; Esfandyari-Manesh, Mehdi; Marashi, Seyyed Mahmoud Amin; Samadi, Nasrin; Fatemi, Seyyed Mostafa; Atyabi, Fatemeh; Eshraghi, Saeed; Dinarvand, Rassoul

2012-01-01

Background Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Methods Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. Results The nanoparticles prepared in this study were spherical, with an average particle size of 85–424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Conclusion Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug. PMID:22275837

PLGA-mPEG nanoparticles of cisplatin: in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties.

PubMed

Avgoustakis, K; Beletsi, A; Panagi, Z; Klepetsanis, P; Karydas, A G; Ithakissios, D S

2002-02-19

The in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties of PLGA-mPEG nanoparticles of cisplatin were investigated. The nanoparticles were prepared by a double emulsion method and characterized with regard to their morphology, size, zeta potential and drug loading. The rate of in vitro degradation of the PLGA-mPEG nanoparticles in PBS (pH 7.4) depended on their composition, increasing when the mPEG content (mPEG:PLGA ratio) of the nanoparticles increased. Sustained cisplatin release over several hours from the PLGA-mPEG nanoparticles in vitro (PBS) was observed. The composition of the nanoparticles affected drug release: the rate of release increased when the mPEG content of the nanoparticles increased. Within the range of drug loadings investigated, the drug loading of the nanoparticles did not have any significant effect on drug release. The loading efficiency was low and needs improvement in order to obtain PLGA-mPEG nanoparticles with a satisfactory cisplatin content for therapeutic application. The i.v. administration of PLGA-mPEG nanoparticles of cisplatin in BALB/c mice resulted in prolonged cisplatin residence in systemic blood circulation. The results appear to justify further investigation of the suitability of the PLGA-mPEG nanoparticles for the controlled i.v. delivery and/or targeting of cisplatin.

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

Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers

PubMed Central

Xiong, Yi; Zhu, Ji-Xiang; Fang, Zheng-Yu; Zeng, Cheng-Guang; Zhang, Chao; Qi, Guo-Long; Li, Man-Hui; Zhang, Wei; Quan, Da-Ping; Wan, Jun

2012-01-01

Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury. PMID:22619535

Cell Attachment and Proliferation of Human Adipose-Derived Stem Cells on PLGA/Chitosan Electrospun Nano-Biocomposite

PubMed Central

Razavi, Shahnaz; Karbasi, Saeed; Morshed, Mohammad; Zarkesh Esfahani, Hamid; Golozar, Mohammad; Vaezifar, Sedigheh

2015-01-01

Objective In this study, nano-biocomposite composed of poly (lactide-co-glycolide) (PLGA) and chitosan (CS) were electrospun through a single nozzle by dispersing the CS nano-powders in PLGA solution. The cellular behavior of human adipose derived stem cells (h-ADSCs) on random and aligned scaffolds was then evaluated. Materials and Methods In this experimental study, the PLGA/CS scaffolds were prepared at the different ratios of 90/10, 80/20, and 70/30 (w/w) %. Morphology, cell adhesion and prolif- eration rate of h-ADSCs on the scaffolds were assessed using scanning electron microscope (SEM), 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and trypan blue staining respectively. Results H-ADSCs seeded on the matrices indicated that the PLGA/CS composite matrix with aligned nanofibres and higher content of CS nano-powders gave significantly better performance than others in terms of cell adhesion and proliferation rate (P<0.05). Conclusion We found that CS enhanced cell adhesion and proliferation rate, and aligned nanofibers guided cell growth along the longitudinal axis of the nanofibers, which would provide a beneficial approach for tissue engineering. PMID:26464814

Prediction of dexamethasone release from PLGA microspheres prepared with polymer blends using a design of experiment approach.

PubMed

Gu, Bing; Burgess, Diane J

2015-11-10

Hydrophobic drug release from poly (lactic-co-glycolic acid) (PLGA) microspheres typically exhibits a tri-phasic profile with a burst release phase followed by a lag phase and a secondary release phase. High burst release can be associated with adverse effects and the efficacy of the formulation cannot be ensured during a long lag phase. Accordingly, the development of a long-acting microsphere product requires optimization of all drug release phases. The purpose of the current study was to investigate whether a blend of low and high molecular weight polymers can be used to reduce the burst release and eliminate/minimize the lag phase. A single emulsion solvent evaporation method was used to prepare microspheres using blends of two PLGA polymers (PLGA5050 (25 kDa) and PLGA9010 (113 kDa)). A central composite design approach was applied to investigate the effect of formulation composition on dexamethasone release from these microspheres. Mathematical models obtained from this design of experiments study were utilized to generate a design space with maximized microsphere drug loading and reduced burst release. Specifically, a drug loading close to 15% can be achieved and a burst release less than 10% when a composition of 80% PLGA9010 and 90 mg of dexamethasone is used. In order to better describe the lag phase, a heat map was generated based on dexamethasone release from the PLGA microsphere/PVA hydrogel composite coatings. Using the heat map an optimized formulation with minimum lag phase was selected. The microspheres were also characterized for particle size/size distribution, thermal properties and morphology. The particle size was demonstrated to be related to the polymer concentration and the ratio of the two polymers but not to the dexamethasone concentration. Copyright © 2015 Elsevier B.V. All rights reserved.

Stimulating effect of graphene oxide on myogenesis of C2C12 myoblasts on RGD peptide-decorated PLGA nanofiber matrices.

PubMed

Shin, Yong Cheol; Lee, Jong Ho; Kim, Min Jeong; Hong, Suck Won; Kim, Bongju; Hyun, Jung Keun; Choi, Yu Suk; Park, Jong-Chul; Han, Dong-Wook

2015-01-01

In the field of biomedical engineering, many studies have focused on the possible applications of graphene and related nanomaterials due to their potential for use as scaffolds, coating materials and delivery carriers. On the other hand, electrospun nanofiber matrices composed of diverse biocompatible polymers have attracted tremendous attention for tissue engineering and regenerative medicine. However, their combination is intriguing and still challenging. In the present study, we fabricated nanofiber matrices composed of M13 bacteriophage with RGD peptide displayed on its surface (RGD-M13 phage) and poly(lactic-co-glycolic acid, PLGA) and characterized their physicochemical properties. In addition, the effect of graphene oxide (GO) on the cellular behaviors of C2C12 myoblasts, which were cultured on PLGA decorated with RGD-M13 phage (RGD/PLGA) nanofiber matrices, was investigated. Our results revealed that the RGD/PLGA nanofiber matrices have suitable physicochemical properties as a tissue engineering scaffold and the growth of C2C12 myoblasts were significantly enhanced on the matrices. Moreover, the myogenic differentiation of C2C12 myoblasts was substantially stimulated when they were cultured on the RGD/PLGA matrices in the presence of GO. In conclusion, these findings propose that the combination of RGD/PLGA nanofiber matrices and GO can be used as a promising strategy for skeletal tissue engineering and regeneration.

Design and characterization of a conductive nanostructured polypyrrole-polycaprolactone coated magnesium/PLGA composite for tissue engineering scaffolds.

PubMed

Liu, Haixia; Wang, Ran; Chu, Henry K; Sun, Dong

2015-09-01

A novel biodegradable and conductive composite consisting of magnesium (Mg), polypyrrole-block-ploycaprolactone (PPy-PCL), and poly(lactic-co-glycolic acid) (PLGA) is synthesized in a core-shell-skeleton manner for tissue engineering applications. Mg particles in the composite are first coated with a conductive nanostructured PPy-PCL layer for corrosion resistance via the UV-induced photopolymerization method. PLGA matrix is then added to tailor the biodegradability of the resultant composite. Composites with different composition ratios are examined through experiments, and their material properties are characterized. The in vitro experiments on culture of 293FT-GFP cells show that the composites are suitable for cell growth and culture. Biodegradability of the composite is also evaluated. By adding PLGA matrix to the composite, the degrading time of the composite can last for more than eight weeks, hence providing a longer period for tissue formation as compared to Mg composites or alloys. The findings of this research will offer a new opportunity to utilize a conductive, nanostructured-coated Mg/PLGA composite as the scaffold material for implants and tissue regeneration. © 2015 Wiley Periodicals, Inc.

Self-Assembly of Porous Boron Nitride Microfibers into Ultralight Multifunctional Foams of Large Sizes.

PubMed

Lin, Jing; Yuan, Xiaohai; Li, Gen; Huang, Yang; Wang, Weijia; He, Xin; Yu, Chao; Fang, Yi; Liu, Zhenya; Tang, Chengchun

2017-12-27

As a kind of macroscopic boron nitride (BN) architectures, ultralight BN cellular materials with high porosity and great resilience would have a broad range of applications in energy and environment areas. However, creating such BN cellular materials in large sizes has still been proven challenging. Here, we report on the unique self-assembly of one-dimensional porous BN microfibers into an integral three-dimensional BN foam with open-cell cellular architectures. An ultrasonic-assisted self-assembly, freeze-drying, and high-temperature pyrolysis process has been developed for the preparation of cellular BN foam with a large size and desired shape. The developed BN foam has low density, high porosity (∼99.3%), great resilience, and excellent hydrophobic-lipophilic nature. The foam also exhibits excellent absorption capacities for a wide range of organic solvents and oils (wt % of ∼5130-7820%), as well as a high recovery efficiency (∼94%). Moreover, the unique hierarchical porous structure enables the foam to demonstrate a very low thermal conductivity (∼0.035 W/K/m). The excellent thermal insulation performance, superior mechanical property, and superb chemical and thermal stability enable the developed BN foam as an integrating multifunctional material in a broad range of high-end applications.

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

Improving bone repair of femoral and radial defects in rabbit by incorporating PRP into PLGA/CPC composite scaffold with unidirectional pore structure.

PubMed

He, Fupo; Chen, Yan; Li, Jiyan; Lin, Bomiao; Ouyang, Yi; Yu, Bo; Xia, Yuanyou; Yu, Bo; Ye, Jiandong

2015-04-01

In this study, a platelet-rich plasma poly(lactic-co-glycolic acid) (PRP-PLGA)/calcium phosphate cement (CPC) composite scaffold was prepared by incorporating PRP into PLGA/CPC scaffold with unidirectional pore structure, which was fabricated by the unidirectional freeze casting of CPC slurry and the following infiltration of PLGA. The results from in vitro cell experiments and in vivo implantation in femoral defects manifested that incorporation of PRP into PLGA/CPC scaffold improved in vitro cell response (cell attachment, proliferation, and differentiation), and markedly boosted bone formation, angiogenesis and material degradation. The incorporation of PRP into scaffold showed more outstanding improvement in osteogenesis as the scaffolds were used to repair the segmental radial defects, especially at the early stage. The new bone tissues grew along the unidirectional lamellar pores of scaffold. At 12 weeks postimplantation, the segmental radial defects treated with PRP-PLGA/CPC scaffold had almost recuperated, whereas treated with the scaffold without PRP was far from healed. Taken together, the PRP-PLGA/CPC scaffold with unidirectional pore structure is a promising candidate to repair bone defects at various sites. © 2014 Wiley Periodicals, Inc.

Poly aspartic acid peptide-linked PLGA based nanoscale particles: potential for bone-targeting drug delivery applications.

PubMed

Jiang, Tao; Yu, Xiaohua; Carbone, Erica J; Nelson, Clarke; Kan, Ho Man; Lo, Kevin W-H

2014-11-20

Delivering drugs specifically to bone tissue is very challenging due to the architecture and structure of bone tissue. Poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) hold great promise for the delivery of therapeutics to bone tissue. The goal of the present research was to formulate a PLGA-based NP drug delivery system for bone tissue exclusively. Since poly-aspartic acids (poly-Asp) peptide sequence has been shown to bind to hydroxyapatite (HA), and has been suggested as a molecular tool for bone-targeting applications, we fabricated PLGA-based NPs linked with poly-Asp peptide sequence. Nanoparticles made of methoxy - poly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged poly-Asp peptide was conjugated to the surface of the nanoparticles via the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the CC double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged poly-Asp peptide to PLGA NPs was confirmed by NMR analysis and fluorescent microscopy. The developed nanoparticle system is highly aqueous dispersible with an average particle size of ∼80 nm. In vitro binding analyses demonstrated that FITC-poly-Asp NPs were able to bind to HA gel as well as to mineralized matrices produced by human mesenchymal stem cells and mouse bone marrow stromal cells. Using a confocal microscopy technique, an ex vivo binding study of mouse major organ ground sections revealed that the FITC-poly-Asp NPs were able to bind specifically to the bone tissue. In addition, proliferation studies indicated that our FITC-poly-Asp NPs did not induce cytotoxicity to human osteoblast-like MG63 cell lines. Altogether, these promising results indicated that this nanoscale targeting system was able to bind to bone tissue specifically and might have a great

Use of PLGA 90:10 scaffolds enriched with in vitro-differentiated neural cells for repairing rat sciatic nerve defects.

PubMed

Luís, Ana L; Rodrigues, Jorge M; Geuna, Stefano; Amado, Sandra; Shirosaki, Yuki; Lee, Jennifer M; Fregnan, Federica; Lopes, Maria A; Veloso, Antonio P; Ferreira, Antonio J; Santos, Jose D; Armada-Da-silva, Paulo A S; Varejão, Artur S P; Maurício, Ana Colette

2008-06-01

Poly(lactic-co-glycolic acid) (PLGA) nerve tube guides, made of a novel proportion (90:10) of the two polymers, poly(L-lactide): poly(glycolide) and covered with a neural cell line differentiated in vitro, were tested in vivo for promoting nerve regeneration across a 10-mm gap of the rat sciatic nerve. Before in vivo testing, the PLGA 90:10 tubes were tested in vitro for water uptake and mass loss and compared with collagen sheets. The water uptake of the PLGA tubes was lower, and the mass loss was more rapid and higher than those of the collagen sheets when immersed in phosphate-buffered saline (PBS) solution. The pH values of immersing PBS did not change after soaking the collagen sheets and showed to be around 7.4. On the other hand, the pH values of PBS after soaking PLGA tubes decreased gradually during 10 days reaching values around 3.5. For the in vivo testing, 22 Sasco Sprague adult rats were divided into four groups--group 1: gap not reconstructed; group 2: gap reconstructed using an autologous nerve graft; group 3: gap reconstructed with PLGA 90:10 tube guides; group 4: gap reconstructed with PLGA 90:10 tube guides covered with neural cells differentiated in vitro. Motor and sensory functional recovery was evaluated throughout a healing period of 20 weeks using sciatic functional index, static sciatic index, extensor postural thrust, withdrawal reflex latency, and ankle kinematics. Stereological analysis was carried out on regenerated nerve fibers. Both motor and sensory functions improved significantly in the three experimental nerve repair groups, although the rate and extent of recovery was significantly higher in the group where the gap was reconstructed using the autologous graft. The presence of neural cells covering the inside of the PLGA tube guides did not make any difference in the functional recovery. By contrast, morphometric analysis showed that the introduction of N1E-115 cells inside PLGA 90:10 tube guides led to a significant lower number

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

Hydrogel-PLGA delivery system prolongs 2-methoxyestradiol-mediated anti-tumor effects in osteosarcoma cells.

PubMed

Maran, Avudaiappan; Dadsetan, Mahrokh; Buenz, Colleen M; Shogren, Kristen L; Lu, Lichun; Yaszemski, Michael J

2013-09-01

Osteosarcoma is a bone tumor that affects children and young adults. 2-Methoxyestradiol (2-ME), a naturally occurring estrogen metabolite, kills osteosarcoma cells, but does not affect normal osteoblasts. In order to effectively target osteosarcoma and improve the therapeutic index of the drug 2-ME, we have encapsulated 2-ME in a composite of oligo-(polyethylene glycol) fumarate (OPF) hydrogel and poly (lactic-co-glycolic acid) (PLGA) microspheres and investigated the effect of polymer composition on 2-ME release kinetics and osteosarcoma cell survival. The in vitro study shows that 2-ME can be released in a controlled manner over 21-days. The initial burst releases observed on day 1 were 50% and 32% for OPF and OPF/PLGA composites, respectively. The extended release kinetics show that 100% of the encapsulated 2-ME is released by day 12 from OPF, whereas the OPF/PLGA composites showed a release of 85% on day 21. 2-ME released from the polymers was biologically active and blocked osteosarcoma cell proliferation in vitro. Also, comparison of 2-ME delivery in osteosarcoma cells in culture, shows that direct treatment has no effect after 3 days, whereas polymer-mediated delivery produces anti-tumor effects that could be sustained for 21 days. These findings show that the OPF and PLGA polymeric system may prove to be useful in controlled and sustained delivery of 2-ME and could be further explored in the treatment of osteosarcoma. Copyright © 2012 Wiley Periodicals, Inc.

Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells

PubMed Central

Mura, Simona; Hillaireau, Herve; Nicolas, Julien; Le Droumaguet, Benjamin; Gueutin, Claire; Zanna, Sandrine; Tsapis, Nicolas; Fattal, Elias

2011-01-01

Background Because of the described hazards related to inhalation of manufactured nanoparticles, we investigated the lung toxicity of biodegradable poly (lactide-co-glycolide) (PLGA) nanoparticles displaying various surface properties on human bronchial Calu-3 cells. Methods Positively and negatively charged as well as neutral nanoparticles were tailored by coating their surface with chitosan, Poloxamer, or poly (vinyl alcohol), respectively. Nanoparticles were characterized in terms of size, zeta potential, and surface chemical composition, confirming modifications provided by hydrophilic polymers. Results Although nanoparticle internalization by lung cells was clearly demonstrated, the cytotoxicity of the nanoparticles was very limited, with an absence of inflammatory response, regardless of the surface properties of the PLGA nanoparticles. Conclusion These in vitro results highlight the safety of biodegradable PLGA nanoparticles in the bronchial epithelium and provide initial data on their potential effects and the risks associated with their use as nanomedicines. PMID:22114491

PLGA Nanoparticles for Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Novel Approach towards Reduction of Renal Radiation Dose

PubMed Central

Arora, Geetanjali; Shukla, Jaya; Ghosh, Sourabh; Maulik, Subir Kumar; Malhotra, Arun; Bandopadhyaya, Gurupad

2012-01-01

Background Peptide receptor radionuclide therapy (PRRT), employed for treatment of neuroendocrine tumors (NETs) is based on over-expression of Somatostatin Receptors (SSTRs) on NETs. It is, however, limited by high uptake and retention of radiolabeled peptide in kidneys resulting in unnecessary radiation exposure thus causing nephrotoxicity. Employing a nanocarrier to deliver PRRT drugs specifically to the tumor can reduce the associated nephrotoxicity. Based on this, 177Lu-DOTATATE loaded PLGA nanoparticles (NPs) were formulated in the present study, as a potential therapeutic model for NETs. Methodology and Findings DOTATATE was labeled with Lutetium-177 (177Lu) (labeling efficiency 98%; Rf∼0.8). Polyethylene Glycol (PEG) coated 177Lu-DOTATATE-PLGA NPs (50∶50 and 75∶25) formulated, were spherical with mean size of 304.5±80.8 and 733.4±101.3 nm (uncoated) and 303.8±67.2 and 494.3±71.8 nm (coated) for PLGA(50∶50) and PLGA(75∶25) respectively. Encapsulation efficiency (EE) and In-vitro release kinetics for uncoated and coated NPs of PLGA (50∶50 & 75∶25) were assessed and compared. Mean EE was 77.375±4.98% & 67.885±5.12% (uncoated) and 65.385±5.67% & 58.495±5.35% (coated). NPs showed initial burst release between 16.64–21.65% with total 42.83–44.79% over 21days. The release increased with coating to 20.4–23.95% initially and 60.97–69.12% over 21days. In-vivo studies were done in rats injected with 177Lu-DOTATATE and 177Lu-DOTATATE-NP (uncoated and PEG-coated) by imaging and organ counting after sacrificing rats at different time points over 24 hr post-injection. With 177Lu-DOTATATE, renal uptake of 37.89±10.2%ID/g was observed, which reduced to 4.6±1.97% and 5.27±1.66%ID/g with uncoated and coated 177Lu-DOTATATE-NP. The high liver uptake with uncoated 177Lu-DOTATATE-NP (13.68±3.08% ID/g), reduced to 7.20±2.04%ID/g (p = 0.02) with PEG coating. Conclusion PLGA NPs were easily formulated and modified for desired release properties

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.

Comparative Efficacies of Collagen-Based 3D Printed PCL/PLGA/β-TCP Composite Block Bone Grafts and Biphasic Calcium Phosphate Bone Substitute for Bone Regeneration.

PubMed

Hwang, Kyoung-Sub; Choi, Jae-Won; Kim, Jae-Hun; Chung, Ho Yun; Jin, Songwan; Shim, Jin-Hyung; Yun, Won-Soo; Jeong, Chang-Mo; Huh, Jung-Bo

2017-04-17

The purpose of this study was to compare bone regeneration and space maintaining ability of three-dimensional (3D) printed bone grafts with conventional biphasic calcium phosphate (BCP). After mixing polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) in a 4:4:2 ratio, PCL/PLGA/β-TCP particulate bone grafts were fabricated using 3D printing technology. Fabricated particulate bone grafts were mixed with atelocollagen to produce collagen-based PCL/PLGA/β-TCP composite block bone grafts. After formation of calvarial defects 8 mm in diameter, PCL/PLGA/β-TCP composite block bone grafts and BCP were implanted into bone defects of 32 rats. Although PCL/PLGA/β-TCP composite block bone grafts were not superior in bone regeneration ability compared to BCP, the results showed relatively similar performance. Furthermore, PCL/PLGA/β-TCP composite block bone grafts showed better ability to maintain bone defects and to support barrier membranes than BCP. Therefore, within the limitations of this study, PCL/PLGA/β-TCP composite block bone grafts could be considered as an alternative to synthetic bone grafts available for clinical use.

Ketamine nano-delivery based on poly-lactic-co-glycolic acid (PLGA) nanoparticles

NASA Astrophysics Data System (ADS)

Hirano, Sota; Bovi, Michele; Romeo, Alessandro; Guzzo, Flavia; Chiamulera, Cristiano; Perduca, Massimiliano

2018-04-01

This work describes a novel method for the generation of a ketamine nano-delivery, to improve brain blood barrier permeability and increase drug therapeutic window as anaesthetic, analgesic and potential antidepressant. The approach herein described is based on ketamine-loaded poly-lactic-co-glycolic acid (PLGA) nanoparticles coupled to an apolipoprotein E (ApoE) peptide for delivery to the central nervous system. PLGA particles were synthesized with amount of drug, coupled with the ApoE peptide on the surface, and validated by physical characterization. The produced nanodevice showed a good colloidal stability in water, confirmed by zeta potential measurements, with a diameter in the range of 185-205 nm. The ketamine encapsulation was verified by liquid chromatography-mass spectrometry analyses obtaining an encapsulation efficiency up to 21.2 ± 3.54%. Once the occurrence of ApoE peptide functionalization was confirmed with fluorescence spectroscopy, the thermal stability and morphological information were obtained by differential scanning calorimetry and further dynamic light scattering measurements. The spherical shape and a rough nanoparticles surface were observed by atomic force microscopy. The reliability of this approach may be further developed as a protocol to be used to generate PLGA nanoparticles greater than 100 nm able to better penetrate blood brain barrier and release a neuroactive molecule at lower doses.

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

Development of biodegradable PLGA nanoparticles surface engineered with hyaluronic acid for targeted delivery of paclitaxel to triple negative breast cancer cells.

PubMed

Cerqueira, Brenda Brenner S; Lasham, Annette; Shelling, Andrew N; Al-Kassas, Raida

2017-07-01

This study aimed at development of poly (lactic-co-glycolic acid) (PLGA) nanoparticles embedded with paclitaxel and coated with hyaluronic acid (HA-PTX-PLGA) to actively target the drug to a triple negative breast cancer cells. Nanoparticles were successfully fabricated using a modified oil-in-water emulsion method. The effect of various formulations parameters on the physicochemical properties of the nanoparticles was investigated. SEM imaging confirmed the spherical shape and nano-scale size of the nanoparticles. A sustained drug release profile was obtained and enhanced PTX cytotoxicity was observed when MDA-MB-231 cells were incubated with the HA-PTX-PLGA formulation compared to cells incubated with the non-HA coated nanoparticles. Moreover, HA-PLGA nanoparticles exhibited improved cellular uptake, based on a possible receptor mediated endocytosis due to interaction of HA with CD44 receptors when compared to non-coated PLGA nanoparticles. The non-haemolytic potential of the nanoparticles indicated the suitability of the developed formulation for intravenous administration. Copyright © 2017 Elsevier B.V. All rights reserved.

The use of BMP-2 coupled – Nanosilver-PLGA composite grafts to induce bone repair in grossly infected segmental defects

PubMed Central

Zheng, Zhong; Yin, Wei; Zara, Janette N.; Li, Weiming; Kwak, Jinny; Mamidi, Rachna; Lee, Min; Siu, Ronald K.; Ngo, Richard; Wang, Joyce; Carpenter, Doug; Zhang, Xinli; Wu, Benjamin; Ting, Kang; Soo, Chia

2010-01-01

Healing of contaminated/infected bone defects is a significant clinical challenge. Prevalence of multi-antibiotic resistant organisms has renewed interest in the use of antiseptic silver as an effective, but less toxic antimicrobial with decreased potential for bacterial resistance. In this study, we demonstrated that metallic nanosilver particles (with a size of 20–40 nm)-poly(lactic-co-glycolic acid) (PLGA) composite grafts have strong antibacterial properties. In addition, nanosilver particles-PLGA composite grafts did not inhibit adherence, proliferation, alkaline phosphatase activity, or mineralization of ongrowth MC3T3-E1 pre-osteoblasts compared to PLGA controls. Furthermore, nanosilver particles did not affect the osteoinductivity of bone morphogenetic protein 2 (BMP-2). Infected femoral defects implanted with BMP-2 coupled 2.0% nanosilver particles-PLGA composite grafts healed in 12 weeks without evidence of residual bacteria. In contrast, BMP-2 coupled PLGA control grafts failed to heal in the presence of continued bacterial colonies. Our results indicate that nanosilver of defined particle size is bactericidal without discernable in vitro and in vivo cytotoxicity or negative effects on BMP-2 osteoinductivity, making it an ideal antimicrobial for bone regeneration in infected wounds. PMID:20864167

Adsorption of plasma proteins on uncoated PLGA nanoparticles.

PubMed

Sempf, Karim; Arrey, Tabiwang; Gelperina, Svetlana; Schorge, Tobias; Meyer, Björn; Karas, Michael; Kreuter, Jörg

2013-09-01

The biodistribution of nanoparticles is significantly influenced by their interaction with plasma proteins. In order to optimize and possibly monitor the delivery of drugs bound to nanoparticles across the blood-brain barrier (BBB), the protein adsorption pattern of uncoated poly(lactic-co-glycolic acid) (PLGA) nanoparticles after their incubation in human plasma was studied by mass spectrometry. After washing of the particles with water, the proteins were directly digested on the nanoparticle surface using trypsin and then analyzed by nLC MALDI-TOF/TOF. Up to now, the standard method for investigation into the plasma protein adsorption to the particles was 2D gel electrophoresis (2D-PAGE), in certain cases followed by mass spectrometry. The non-gel-based method proposed in the present study provides novel insights into the protein corona surrounding the nanoparticles. The proteins adsorbed on the PLGA nanoparticles after incubation that gave the best signal in terms of quality (high MASCOT score) in human plasma were apolipoprotein E, vitronectin, histidine-rich glycoprotein and kininogen-1. These proteins also are constituents of HDL. Copyright © 2013 Elsevier B.V. All rights reserved.

Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

PubMed

Manna, Soumyarwit; Donnell, Anna M; Kaval, Necati; Al-Rjoub, Marwan F; Augsburger, James J; Banerjee, Rupak K

2018-05-29

Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases. Copyright © 2018. Published by Elsevier B.V.

Development of PLGA-coated β-TCP scaffolds containing VEGF for bone tissue engineering.

PubMed

Khojasteh, Arash; Fahimipour, Farahnaz; Eslaminejad, Mohamadreza Baghaban; Jafarian, Mohammad; Jahangir, Shahrbanoo; Bastami, Farshid; Tahriri, Mohammadreza; Karkhaneh, Akbar; Tayebi, Lobat

2016-12-01

Bone tissue engineering is sought to apply strategies for bone defects healing without limitations and short-comings of using either bone autografts or allografts and xenografts. The aim of this study was to fabricate a thin layer poly(lactic-co-glycolic) acid (PLGA) coated beta-tricalcium phosphate (β-TCP) scaffold with sustained release of vascular endothelial growth factor (VEGF). PLGA coating increased compressive strength of the β-TCP scaffolds significantly. For in vitro evaluations, canine mesenchymal stem cells (cMSCs) and canine endothelial progenitor cells (cEPCs) were isolated and characterized. Cell proliferation and attachment were demonstrated and the rate of cells proliferation on the VEGF released scaffold was significantly more than compared to the scaffolds with no VEGF loading. A significant increase in expression of COL1 and RUNX2 was indicated in the scaffolds loaded with VEGF and MSCs compared to the other groups. Consequently, PLGA coated β-TCP scaffold with sustained and localized release of VEGF showed favourable results for bone regeneration in vitro, and this scaffold has the potential to use as a drug delivery device in the future. Copyright © 2016. Published by Elsevier B.V.

Evaluation of an injectable rhGDF-5/PLGA construct for minimally invasive periodontal regenerative procedures: a histological study in the dog.

PubMed

Kwon, David H; Bennett, William; Herberg, Samuel; Bastone, Patrizia; Pippig, Susanne; Rodriguez, Nancy A; Susin, Cristiano; Wikesjö, Ulf M E

2010-04-01

To evaluate the injectability, biocompatibility, safety, and periodontal wound healing/regeneration following application of a novel bioresorbable recombinant human growth/differentiation factor-5 (rhGDF-5)/poly(lactic-co-glycolic acid) (PLGA) construct. Periodontal pockets (3 x 6 mm, width x depth) were surgically created over the buccal roots of the second and fourth mandibular pre-molars in eight adult Hound Labrador mongrel dogs. Surgeries including injection of the rhGDF-5/PLGA construct into the pockets were sequenced that four animals provided 2-/4-week and four animals 6-/8-week observations of sites receiving rhGDF-5/PLGA or serving as sham-surgery control. The rhGDF-5/PLGA construct was easy to prepare and apply. Approximately 0.2 ml (93 microg rhGDF-5)/tooth was used. Clinical and radiographic healing was exemplary without adverse events. Healing was characterized by a non-specific connective tissue attachment, acellular/cellular cementum, periodontal ligament (PDL), bone regeneration, and a junctional epithelium. PLGA fragments were observed in 4/7, 2/8, and 1/8 sites at 2, 4, and 6 weeks, respectively. Associated inflammatory reactions exhibited no limiting effect on periodontal wound healing/regeneration. Root resorption/ankylosis was not observed. Bone formation showed apparent increased maturity (lamellar bone) at 6 weeks in sites receiving rhGDF-5/PLGA compared with the control. Both protocols exhibited significant increases in PDL, cementum, and bone regeneration over time, without significant differences between treatments. In time, PDL and cementum regeneration was twofold greater for the control at 4 weeks (p=0.04) while increased bone formation was observed at sites receiving rhGDF-5/PLGA (p<0.01). In conclusion, the rhGDF-5/PLGA construct appears to be a safe technology for injectable, ease-of-use application of rhGDF-5-stimulated periodontal wound healing/regeneration. Additional work to optimize the polymer carrier and rhGDF-5 release

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

PubMed

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.

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

Hierarchical porous carbon microspheres derived from porous starch for use in high-rate electrochemical double-layer capacitors.

PubMed

Du, Si-Hong; Wang, Li-Qun; Fu, Xiao-Ting; Chen, Ming-Ming; Wang, Cheng-Yang

2013-07-01

Porous starch was used as a precursor for hierarchical porous carbon microspheres. The preparation consisted of stabilisation, carbonisation and KOH activation, and the resultant hierarchical porous carbon microspheres had a large BET surface area of 3251 m(2)g(-1). Due to the large surface area and the hierarchical pore structure, electrodes made of the hierarchical porous carbon microsphere materials had high specific capacitances of 304 Fg(-1) at a current density of 0.05 Ag(-1) and 197 Fg(-1) at a current density of 180 Ag(-1) when used in a symmetric capacitor with 6M KOH as the electrolyte. After 10,000 cycles, the capacitor still exhibited a stable performance with a capacitance retention of 98%. These results indicate that porous starch is an excellent precursor to prepare high performance electrode materials for EDLCs. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed

Ma, Jing; Shen, Ming; Xu, Chang Song; Sun, Ying; Duan, You Rong; Du, Lian Fang

2016-11-29

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.

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.

L-Valine appended PLGA nanoparticles for oral insulin delivery.

PubMed

Jain, Ashish; Jain, Sanjay K

2015-08-01

Oral insulin delivery has been the major research issue, since many decades, due to several obvious advantages over other routes. However, this route poses several constraints for the delivery of peptides and proteins which are to be worked upon. The small intestine has been shown to be able to transport the L-forms of amino acids against a concentration gradient and that they compete for the mechanism concerned. So, L-valine was used as a ligand for carrier-mediated transport of insulin-loaded polylactic-co-glycolic acid (PLGA) nanoparticles (NPs). L-Valine-conjugated PLGA nanoparticles were prepared using double emulsion solvent evaporation method. The NPs and conjugated NPs were characterized for their size, drug entrapment efficiency, zeta potential, polydispersity index and in vitro insulin release. Ex vivo studies on intestine revealed that conjugated nanoparticles showed greater insulin uptake as compared to non-conjugated nanoparticles. In vivo studies were performed on streptozotocin-induced diabetic rabbits. Oral suspension of insulin-loaded PLGA nanoparticles reduced blood glucose level from 265.4 ± 8.5 to 246.6 ± 2.4 mg/dL within 4 h which further decreased to 198.7 ± 7.1 mg/dL value after 8 h. The ligand-conjugated formulation on oral administration produced hypoglycaemic effect (216.9 ± 1.9 mg/dL) within 4 h of administration, and the hypoglycaemic effect prolonged till 12 h of oral administration. Simultaneously, the insulin concentration in withdrawn samples was also assessed and found that profile of insulin level is in compliance with the blood glucose reduction profile. Hence, it is concluded that the L-valine-conjugated NPs bearing insulin are the promising carrier for the transportation of insulin across the intestine on oral administration.

Bone regeneration of critical calvarial defect in goat model by PLGA/TCP/rhBMP-2 scaffolds prepared by low-temperature rapid-prototyping technology.

PubMed

Yu, D; Li, Q; Mu, X; Chang, T; Xiong, Z

2008-10-01

Active artificial bone composed of poly lactide-co-glycolide (PLGA)/ tricalcium phosphate (TCP) was prefabricated using low-temperature rapid-prototyping technology so that the process of osteogenesis could be observed in it. PLGA and TCP were the primary materials, they were molded at low temperature, then recombinant human bone morphogenetic protein-2 (rhBMP-2) was added to form an active artificial bone. Goats with standard cranial defects were randomly divided into experimental (implants with rhBMP-2 added) and control (implants without rhBMP-2) groups, and osteogenesis was observed and evaluated by imaging and biomechanical and histological examinations. The PLGA-TCP artificial bone scaffold (90% porosity) had large and small pores of approximately 360microm and 3-5microm diameter. Preliminary and complete repair of the cranial defect in the goats occurred 12 and 24 weeks after surgery, respectively. The three-point bending strength of the repaired defects attained that of the normal cranium. In conclusion, low-temperature rapid-prototyping technology can preserve the biological activity of this scaffold material. The scaffold has a good three-dimensional structure and it becomes an active artificial bone after loading with rhBMP-2 with a modest degradation rate and excellent osteogenesis in the goat.

Methotrexate-loaded PLGA nanobubbles for ultrasound imaging and Synergistic Targeted therapy of residual tumor during HIFU ablation.

PubMed

Zhang, Xuemei; Zheng, Yuanyi; Wang, Zhigang; Huang, Shuai; Chen, Yu; Jiang, Wei; Zhang, Hua; Ding, Mingxia; Li, Qingshu; Xiao, Xiaoqiu; Luo, Xin; Wang, Zhibiao; Qi, Hongbo

2014-06-01

High intensity focused ultrasound (HIFU) has attracted the great attention in tumor ablation due to its non-invasive, efficient and economic features. However, HIFU ablation has its intrinsic limitations for removing the residual tumor cells, thus the tumor recurrence and metastasis cannot be avoided in this case. Herein, we developed a multifunctional targeted poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs), which not only function as an efficient ultrasound contrast agent for tumor imaging, but also a targeted anticancer drug carrier and excellent synergistic agent for enhancing the therapeutic efficiency of HIFU ablation. Methotrexate (MTX)-loaded NBs were synthesized and filled with perfluorocarbon gas subsequently using a facile but general double emulsion evaporation method. The active tumor-targeting monoclonal anti-HLA-G antibodies (mAbHLA-G) were further conjugated onto the surface of nanobubbles. The mAbHLA-G/MTX/PLGA NBs could enhance the ultrasound imaging both in vitro and in vivo, and the targeting efficiency to HLA-G overexpressing JEG-3 cells has been demonstrated. The elaborately designed mAbHLA-G/MTX/PLGA NBs can specifically target to the tumor cells both in vitro and in vivo, and their blood circulation time in vivo was much longer than non-targeted MTX/PLGA NBs. Further therapeutic evaluations showed that the targeted NBs as a synergistic agent can significantly improve the efficiency of HIFU ablation by changing the acoustic environment, and the focused ultrasound can promote the on-demand MTX release both in vitro and in vivo. The in vivo histopathology test and immunohistochemical analysis showed that the mAbHLA-G/MTX/PLGA NBs plus HIFU group presented most serious coagulative necrosis, the lowest proliferation index and the highest apoptotic index. Therefore, the successful introduction of targeted mAbHLA-G/MTX/PLGA NBs provides an excellent platform for the highly efficient, imaging-guided and non-invasive HIFU synergistic therapy

Injectable controlled release depots for large molecules

PubMed Central

Schwendeman, Steven P.; Shah, Ronak B.; Bailey, Brittany A.; Schwendeman, Anna S.

2014-01-01

Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development. PMID:24929039

Activation of Antigen-Specific CD8(+) T Cells by Poly-DL-Lactide/Glycolide (PLGA) Nanoparticle-Primed Gr-1(high) Cells.

PubMed

Luo, Wen-Hui; Yang, Ya-Wun

2016-04-01

The aim of this study was to investigate the induction of antigen-specific T cell activation and cell cycle modulation by a poly-DL-lactide/glycolide (PLGA) nanoparticle (NP)-primed CD11b(+)Gr-1(high) subset isolated from mouse bone marrow. PLGA NPs containing the ovalbumin (OVA) antigen were prepared using the double emulsion and solvent evaporation method, and protein release rate and cell viability were determined. The Lin2(¯)CD11b(+)Gr-1(high)Ly6c(low) (Gr-1(high)) subset was sorted from the bone marrow of C57BL/6 J mice by fluorescence-activated cell sorting (FACS) and co-cultured with OT-I CD8(+) splenic T cells. Proliferation of OT-I CD8(+) T cells was monitored, and cell cycles were determined by 5-bromo-2'-deoxyuridine (BrdU) labeling. Treatment of Gr-1(high) cells with PLGA/OVA NPs upregulated expression of the SIINFEKL-H2K(b) complex in the context of MHC I. Co-cultures of OT-I CD8(+) T cells with the PLGA/OVA NP-primed Gr-1(high) cells induced the proliferation of T cells in vitro and modulated cell division and morphology. Treatment of Gr-1(high) cells with PLGA/OVA NPs also induced cell apoptosis and necrosis. This study demonstrated the function of PLGA/OVA NPs in the activation of OT-I CD8(+) T cells and the capability of cross-presentation via the Gr-1(high) polymorphonuclear subset from mouse bone marrow.

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

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

Semete, B., E-mail: Bsemete@csir.co.z; Booysen, L.I.J.; Department of Pharmaceutics, North-West University, Potchefstroom Campus, Potchefstroom, 2520

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 nanoparticlesmore » 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.« less

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

PubMed

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

2012-11-01

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

Nanostructural characterization of large-scale porous alumina fabricated via anodizing in arsenic acid solution

NASA Astrophysics Data System (ADS)

Akiya, Shunta; Kikuchi, Tatsuya; Natsui, Shungo; Suzuki, Ryosuke O.

2017-05-01

Anodizing of aluminum in an arsenic acid solution is reported for the fabrication of anodic porous alumina. The highest potential difference (voltage) without oxide burning increased as the temperature and the concentration of the arsenic acid solution decreased, and a high anodizing potential difference of 340 V was achieved. An ordered porous alumina with several tens of cells was formed in 0.1-0.5 M arsenic acid solutions at 310-340 V for 20 h. However, the regularity of the porous alumina was not improved via anodizing for 72 h. No pore sealing behavior of the porous alumina was observed upon immersion in boiling distilled water, and it may be due to the formation of an insoluble complex on the oxide surface. The porous alumina consisted of two different layers: a hexagonal alumina layer that contained arsenic from the electrolyte and a pure alumina honeycomb skeleton. The porous alumina exhibited a white photoluminescence emission at approximately 515 nm under UV irradiation at 254 nm.

Multifunctional PLGA Nanobubbles as Theranostic Agents: Combining Doxorubicin and P-gp siRNA Co-Delivery Into Human Breast Cancer Cells and Ultrasound Cellular Imaging.

PubMed

Yang, Hong; Deng, Liwei; Li, Tingting; Shen, Xue; Yan, Jie; Zuo, Liangming; Wu, Chunhui; Liu, Yiyao

2015-12-01

Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. One of the effective approaches to overcome MDR is to use nanoparticle-mediated the gene silence of chemotherapeutic export proteins by RNA interference to increase drug accumulation in drug resistant cancer cells. In this work, a new co-delivery system, DOX-PLGA/PEI/P-gp shRNA nanobubbles (NBs) around 327 nm, to overcome doxorubicin (DOX) resistance in MCF-7 human breast cancer was designed and developed. Positively charged polyethylenimine (PEI) were modified onto the surface of DOX-PLGA NBs through DCC/NHS crosslinking, and could efficiently condense P-gp shRNA into DOX-PLGA/PEI NBs at vector/shRNA weight ratios of 70:1 and above. An in vitro release profile demonstrated an efficient DOX release (more than 80%) from DOX-PLGA/PEI NBs at pH 4.4, suggesting a pH-responsive drug release for the multifunctionalized NBs. Cellular experimental results further showed that DOX-PLGA/PEI/P-gp shRNA NBs could facilitate cellular uptake of DOX into cells and increase the cell proliferation suppression effect of DOX against MCF-7/ADR cells (a DOX-resistant and P-glycoprotein (P-gp) over-expression cancer cell line). The IC50 of DOX-PLGA NBs against MCF-7/ADR cells was 2-fold lower than that of free DOX. The increased cellular uptake and nuclear accumulation of DOX delivered by DOX-PLGA/PEI/P-gp shRNA NBs in MCF-7/ADR cells was confirmed by fluorescence microscopy and fluorescence spectrophotometry, and might be owning to the down-regulation of P-gp and reduced the efflux of DOX. The cellular uptake mechanism of DOX-PLGA/PEI/P-gp shRNA NBs indicated that the macropinocytosis was one of the pathways for the uptake of NBs by MCF-7/ADR cells, which was also an energy-dependent process. Furthermore, the in vitro cellular ultrasound imaging suggested that the employment of the DOX-PLGA/PEI/P-gp shRNA NBs could efficiently enhance ultrasound imaging of cancer cells. These results demonstrated

Microwave Assisted Synthesis of Porous NiCo2O4 Microspheres: Application as High Performance Asymmetric and Symmetric Supercapacitors with Large Areal Capacitance

PubMed Central

Khalid, Syed; Cao, Chuanbao; Wang, Lin; Zhu, Youqi

2016-01-01

Large areal capacitance is essentially required to integrate the energy storage devices at the microscale electronic appliances. Energy storage devices based on metal oxides are mostly fabricated with low mass loading per unit area which demonstrated low areal capacitance. It is still a challenge to fabricate supercapacitor devices of porous metal oxides with large areal capacitance. Herein we report microwave method followed by a pyrolysis of the as-prepared precursor is used to synthesize porous nickel cobaltite microspheres. Porous NiCo2O4 microspheres are capable to deliver large areal capacitance due to their high specific surface area and small crystallite size. The facile strategy is successfully demonstrated to fabricate aqueous-based asymmetric & symmetric supercapacitor devices of porous NiCo2O4 microspheres with high mass loading of electroactive materials. The asymmetric & symmetric devices exhibit maximum areal capacitance and energy density of 380 mF cm−2 & 19.1 Wh Kg−1 and 194 mF cm−2 & 4.5 Wh Kg−1 (based on total mass loading of 6.25 & 6.0 mg) respectively at current density of 1 mA cm−2. The successful fabrication of symmetric device also indicates that NiCo2O4 can also be used as the negative electrode material for futuristic asymmetric devices. PMID:26936283

Microwave Assisted Synthesis of Porous NiCo2O4 Microspheres: Application as High Performance Asymmetric and Symmetric Supercapacitors with Large Areal Capacitance

NASA Astrophysics Data System (ADS)

Khalid, Syed; Cao, Chuanbao; Wang, Lin; Zhu, Youqi

2016-03-01

Large areal capacitance is essentially required to integrate the energy storage devices at the microscale electronic appliances. Energy storage devices based on metal oxides are mostly fabricated with low mass loading per unit area which demonstrated low areal capacitance. It is still a challenge to fabricate supercapacitor devices of porous metal oxides with large areal capacitance. Herein we report microwave method followed by a pyrolysis of the as-prepared precursor is used to synthesize porous nickel cobaltite microspheres. Porous NiCo2O4 microspheres are capable to deliver large areal capacitance due to their high specific surface area and small crystallite size. The facile strategy is successfully demonstrated to fabricate aqueous-based asymmetric & symmetric supercapacitor devices of porous NiCo2O4 microspheres with high mass loading of electroactive materials. The asymmetric & symmetric devices exhibit maximum areal capacitance and energy density of 380 mF cm-2 & 19.1 Wh Kg-1 and 194 mF cm-2 & 4.5 Wh Kg-1 (based on total mass loading of 6.25 & 6.0 mg) respectively at current density of 1 mA cm-2. The successful fabrication of symmetric device also indicates that NiCo2O4 can also be used as the negative electrode material for futuristic asymmetric devices.

Enhanced biocompatibility of PLGA nanofibers with gelatin/nano-hydroxyapatite bone biomimetics incorporation.

PubMed

Li, Daowei; Sun, Haizhu; Jiang, Liming; Zhang, Kai; Liu, Wendong; Zhu, Yang; Fangteng, Jiaozi; Shi, Ce; Zhao, Liang; Sun, Hongchen; Yang, Bai

2014-06-25

The biocompatibility of biomaterials is essentially for its application. The aim of current study was to evaluate the biocompatibility of poly(lactic-co-glycolic acid) (PLGA)/gelatin/nanohydroxyapatite (n-HA) (PGH) nanofibers systemically to provide further rationales for the application of the composite electrospun fibers as a favorable platform for bone tissue engineering. The PGH composite scaffold with diameter ranging from nano- to micrometers was fabricated by using electrospinning technique. Subsequently, we utilized confocal laser scanning microscopy (CLSM) and MTT assay to evaluate its cyto-compatibility in vitro. Besides, real-time quantitative polymerase chain reaction (qPCR) analysis and alizarin red staining (ARS) were performed to assess the osteoinductive activity. To further test in vivo, we implanted either PLGA or PGH composite scaffold in a rat subcutaneous model. The results demonstrated that PGH scaffold could better support osteoblasts adhesion, spreading, and proliferation and show better cyto-compatibility than pure PLGA scaffold. Besides, qPCR analysis and ARS showed that PGH composite scaffold exhibited higher osteoinductive activity owing to higher phenotypic expression of typical osteogenic genes and calcium deposition. The histology evaluation indicated that the incorporation of Gelatin/nanohydroxyapatite (GH) biomimetics could significantly reduce local inflammation. Our data indicated that PGH composite electrospun nanofibers possessed excellent cyto-compatibility, good osteogenic activity, as well as good performance of host tissue response, which could be versatile biocompatible scaffolds for bone tissue engineering.

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

Scolicidal and apoptotic activities of albendazole sulfoxide and albendazole sulfoxide-loaded PLGA-PEG as a novel nanopolymeric particle against Echinococcus granulosus protoscoleces.

PubMed

Naseri, Marziyeh; Akbarzadeh, Abolfazl; Spotin, Adel; Akbari, Nagibeh Asl Rahnemaii; Mahami-Oskouei, Mahmoud; Ahmadpour, Ehsan

2016-12-01

Treatment failures of human cystic echinococcosis (CE) with albendazole (ABZ) have attributed to its low solubility and poor drug absorption rate, resulting in low drug level in plasma. The scolicidal effects of ABZ-loaded liposome nanoparticles have recently evaluated; however, these particles have several challenges due to their low encapsulated load. This investigation was designed to evaluate and compare in vitro apoptotic activities of ABZ sulfoxide (ABZs) and ABZs-loaded poly(lactic-co-glycolic acid) (PLGA)-PEG against protoscoleces (PSCs). ABZs-loaded PLGA-PEG was prepared by a double-emulsion method (W1/O/W2). Various concentrations of ABZs and ABZs-loaded PLGA-PEG (50, 100, 150, and 200 μg/ml) were experimentally tested against PSC of CE at different exposure times (5, 10, 20, 30, and 60 min). ABZs-loaded PLGA-PEG at concentrations of 150 and 200 μg/ml was able to act at a 100 % scolicidal rate in all exposure times (5 to 60 min), while ABZs at a concentration of 200 μg/ml demonstrated 94, 100, and 100 % mortality rates following 20, 30, and 60 min of exposure times, respectively. The messenger RNA (mRNA) expression of caspase-3 was assessed by semi-quantitative RT-PCR after 15 h of exposure. Caspase-3 mRNA expression was higher in both PSC treated with ABZs and PSC treated with ABZs-loaded PLGA-PEG than that in control groups (P < 0.05). No significant difference was observed between the apoptotic intensity of PSC treated with ABZs and that of PSC treated with ABZs-loaded PLGA-PEG (P > 0.05). DNA fragmentation assay and ultrastructural changes revealed that ABZs and ABZs-loaded PLGA-PEG induced the apoptosis of PSC by activation of caspase-3. The higher permeability and scolicidal rate of ABZs-loaded PLGA-PEG can be addressed as an effectual alternative strategy to improve the treatment of human CE.

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. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fabrication of highly uniform and porous MgF2 anti-reflective coatings by polymer-based sol-gel processing on large-area glass substrates.

PubMed

Raut, Hemant Kumar; Dinachali, Saman Safari; Ansah-Antwi, Kwadwo Konadu; Ganesh, V Anand; Ramakrishna, Seeram

2013-12-20

Despite recent progress in the fabrication of magnesium fluoride (MgF2) anti-reflective coatings (ARCs), simple, effective and scalable sol-gel fabrication of MgF2 ARCs for large-area glass substrates has prospective application in various optoelectronic devices. In this paper, a polymer-based sol-gel route was devised to fabricate highly uniform and porous MgF2 ARCs on large-area glass substrates. A sol-gel precursor made of polyvinyl acetate and magnesium trifluoroacetate assisted in the formation of uniformly mesoporous MgF2 ARCs on glass substrates, leading to the attainment of a refractive index of ~1.23. Systematic optimization of the thickness of the ARC in the sub-wavelength regime led to achieving ~99.4% transmittance in the case of the porous MgF2 ARC glass. Precise control of the thickness of porous MgF2 ARC glass also resulted in a mere ~0.1% reflection, virtually eliminating reflection off the glass surface at the target wavelength. Further manipulation of the thickness of the ARC on either side of the glass substrate led to the fabrication of relatively broadband, porous MgF2 ARC glass.

Enhanced bone regeneration using an insulin-loaded nano-hydroxyapatite/collagen/PLGA composite scaffold.

PubMed

Wang, Xing; Zhang, Guilan; Qi, Feng; Cheng, Yongfeng; Lu, Xuguang; Wang, Lu; Zhao, Jing; Zhao, Bin

2018-01-01

Insulin is widely considered as a classical hormone and drug in maintaining energy and glucose homeostasis. Recently, insulin has been increasingly recognized as an indispensable factor for osteogenesis and bone turnover, but its applications in bone regeneration have been restricted because of the short periods of activity and uncontrolled release. In this study, we incorporated insulin-loaded poly lactic-co-glycolic-acid (PLGA) nanospheres into nano-hydroxyapatite/collagen (nHAC) scaffolds and investigated the bioactivity of the composite scaffolds in vitro and in vivo. Bioactive insulin was successfully released from the nanospheres within the scaffold, and the release kinetics of insulin could be efficiently controlled by uniform-sized nanospheres. The physical characterizations of the composite scaffolds demonstrated that incorporation of nanospheres in nHAC scaffolds using this method did not significantly change the porosity, pore diameters, and compressive strengths of nHAC. In vitro, the insulin-loaded nHAC/PLGA composite scaffolds possessed favorable biological function for bone marrow mesenchymal stem cells adhesion and proliferation, as well as the differentiation into osteoblasts. In vivo, the optimized bone regenerative capability of this composite scaffold was confirmed in rabbit mandible critical size defects. These results demonstrated successful development of a functional insulin-PLGA-nHAC composite scaffold that enhances the bone regeneration capability of nHAC.

Zinc phthalocyanine-loaded PLGA biodegradable nanoparticles for photodynamic therapy in tumor-bearing mice.

PubMed

Fadel, Maha; Kassab, Kawser; Fadeel, Doa Abdel

2010-03-01

Nanoparticles formulated from the biodegradable copolymer poly(lactic-coglycolic acid) (PLGA) were investigated as a drug delivery system to enhance tissue uptake, permeation, and targeting of zinc(II) phthalocyanine (ZnPc) for photodynamic therapy. Three ZnPc nanoparticle formulations were prepared using a solvent emulsion evaporation method and the influence of sonication time on nanoparticle shape, encapsulation and size distribution, in vitro release, and in vivo photodynamic efficiency in tumor-bearing mice were studied. Sonication time did not affect the process yield or encapsulation efficiency, but did affect significantly the particle size. Sonication for 20 min reduced the mean particle size to 374.3 nm and the in vitro release studies demonstrated a controlled release profile of ZnPc. Tumor-bearing mice injected with ZnPc nanoparticles exhibited significantly smaller mean tumor volume, increased tumor growth delay and longer survival compared with the control group and the group injected with free ZnPc during the time course of the experiment. Histopathological examination of tumor from animals treated with PLGA ZnPc showed regression of tumor cells, in contrast to those obtained from animals treated with free ZnPc. The results indicate that ZnPc encapsulated in PLGA nanoparticles is a successful delivery system for improving photodynamic activity in the target tissue.

Comparison of PLGA and lecithin/chitosan nanoparticles for dermal targeting of betamethasone valerate.

PubMed

Özcan, Ipek; Azizoğlu, Erkan; Senyiğit, Taner; Özyazici, Mine; Özer, Özgen

2013-07-01

Poly(lactide-co-glycolide) (PLGA) and lecithin/chitosan (LC) nanoparticles were prepared to evaluate the difference in the behavior upon administration on skin, for steroidal treatment. For this purpose, betamethasone-17-valerate (BMV)-loaded nanoparticles with a narrow size distribution and high entrapment efficiency were prepared. Permeation studies showed that both polymeric nanoparticles enhanced the amount of BMV in epidermis, which is the target site of topical steroidal treatment, when compared with commercial formulation. 1.58-Fold increase was determined in the epidermis concentration of BMV by LC nanoparticles with respect to PLGA nanoparticles. Nanoparticles were diluted in chitosan gel (10%, w/w) to prepare suitable formulation for topical application. Accumulation from both gel formulations were found significantly higher than commercial formulation in skin layers (p < 0.05). In addition, pharmacodynamic responses were also investigated as anti-inflammatory and skin-blanching parameters. Both formulations significantly improved these parameters although they contained 10 times less amount of BMV than commercial cream. Moreover, TEWL measurement exhibited no barrier function changes upon the application of nanoparticles on skin. Overall, both nanoparticles improved the localization of BMV within skin layers; but when compared with PLGA nanoparticles, the LC nanoparticles could be classified as a better candidate for topical delivery vehicle in the treatment of various dermatological inflammatory diseases.

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

PubMed Central

Halayqa, Mohammed; Domańska, Urszula

2014-01-01

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

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

PubMed

Halayqa, Mohammed; Domańska, Urszula

2014-12-22

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

Ridge Preservation After Maxillary Third Molar Extraction Using 30% Porosity PLGA/HA/β-TCP Scaffolds With and Without Simvastatin: A Pilot Randomized Controlled Clinical Trial.

PubMed

Noronha Oliveira, Miguel; Rau, Levy Hermes; Marodin, Aline; Corrêa, Márcio; Corrêa, Letícia Ruhland; Aragones, Aguedo; Magini, Ricardo de Souza

2017-12-01

To evaluate clinically and radiographically, in humans, the healing of maxillary third molars postextraction sockets after application of different ridge preservation techniques 3 months after tooth extraction. Twenty-six sockets (13 patients) were randomly assigned to 4 treatment modalities: deproteinized bovine bone mineral with 10% collagen (DBBM-C), poly(D,L-lactide-co-glycolide) with hydroxyapatite/β-TCP scaffold (PLGA/HA), PLGA/HA/β-TCP with 2.0% simvastatin scaffold (PLGA/HA/S), and spontaneous healing (control). Clinical complications were assessed, and cone-beam computed tomographies were taken in 5 patients 3 months after surgeries. For statistical purposes, the Fisher exact test was used (P < 0.05). After 3 months, 6 of 9 grafts from the PLGA/HA group were lost (P < 0.05). PLGA/HA/S' loss was only 2 of 8 (P > 0.05), but no loss was observed in the DBBM-C group. Pain was present in 3 of 8 sites that lost the graft (37.5%) (P > 0.05) and infection in 1 of 8 (12.5%) (P > 0.05), with these only occurring in the PLGA/HA group. Poly (D, L-lactide-co-glycolide) with hydroxyapatite/β-TCP (PLGA/HA/β-TCP) scaffolds, with and without simvastatin, failed to obtain the initial expected results and presented more complications. Scaffolds with simvastatin showed to be superior, with less clinical complications than scaffolds without simvastatin.

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

The influence of silanisation on the mechanical and degradation behaviour of PLGA/HA composites.

PubMed

Naik, Ashutosh; Best, Serena M; Cameron, Ruth E

2015-03-01

This study investigates the influence of silanisation on the mechanical and degradation behaviour of PLGA/HA composites. Three different silanes (mercaptopropyl trimethoxy silane (MPTMS), aminopropyl trimethoxy silane (APTMS) and aminopropyltriethoxy silane (APTES)) were applied to HA substrates in order to study the effect of head group (which binds to the polymer) and tail group (which binds to the surface hydroxyl groups in HA). A composite of hydroxyapatite (HA) and poly(d,l lactide-co-glycolide (50:50)) (PLGA) was investigated. The influence of concentration, the reaction time, drying temperature and substrate surface on silanisation was examined. TGA was used to detect the degree of silanisation. HA with MPTMS (1wt.% MPTMS with reaction time of 1h) was used as filler in PLGA-30wt.% HA composites for an in-vitro degradation study carried out in PBS. In addition, the mechanical properties of the composites were studied. Silanisation affects the properties of the composite by improving the bonding at the interface and hence it was found to influence the plastic mechanical properties rather than the elastic mechanical properties or the degradation profile of the composite. Copyright © 2014. Published by Elsevier B.V.

The inhibitory effect of disulfiram encapsulated PLGA NPs on tumor growth: Different administration routes.

PubMed

Fasehee, Hamidreza; Zarrinrad, Ghazaleh; Tavangar, Seyed Mohammad; Ghaffari, Seyed Hamidollah; Faghihi, Shahab

2016-06-01

The strong anticancer activity of disulfiram is hindered by its rapid degradation in blood system. A novel folate-receptor-targeted poly (lactide-co-glycolide) (PLGA)-polyethylene glycol (PEG) nanoparticle (NP) is developed for encapsulation and delivery of disulfiram into breast cancer tumor using passive (EPR effect) and active (folate receptor) targeting. The anticancer activity of disulfiram and its effect on caspase-3 activity and cell cycle are studied. The administration of encapsulated PLGA NPs using intra-peritoneal, intravenous and intra-tumor routes is investigated using animal model. Disulfiram shows strong cytotoxicity against MCF7 cell line. The activity of caspase-3 inhibited with disulfiram via dose dependent manner while the drug causes cell cycle arrest in G0/G1 and S phase time-dependently. The encapsulated disulfiram shows higher activity in apoptosis induction as compared to free drug. In nontoxic dose of encapsulated disulfiram, the highest and lowest efficacy of NPs in tumor growth inhibition is observed for intravenous injection and intraperitoneal injection. It is suggested that administration of disulfiram by targeted PLGA nanoparticles using intravenous injection would present an alternative therapeutic approach for solid tumor treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Three-dimensional culture of rat calvarial osteoblasts in porous biodegradable polymers

NASA Technical Reports Server (NTRS)

Ishaug-Riley, S. L.; Crane-Kruger, G. M.; Yaszemski, M. J.; Mikos, A. G.

1998-01-01

Neonatal rat calvarial osteoblasts were cultured in 90% porous, 75:25 poly(DL-lactic-co-glycolic acid) (PLGA) foam scaffolds for up to 56 days to examine the effects of the cell seeding density, scaffold pore size, and foam thickness on the proliferation and function of the cells in this three-dimensional environment. Osteoblasts were seeded at either 11.1 x 10(5) or 22.1 x 10(5) cells per cm2 onto PLGA scaffolds having pore sizes in the range of 150-300 or 500-710 microm with a thickness of either 1.9 or 3.2 mm. After 1 day in culture, 75.6 and 68.6% of the seeded cells attached and proliferated on the 1.9 mm thick scaffolds of 150-300 microm pore size for the low and high seeding densities, respectively. The number of osteoblasts continued to increase throughout the study and eventually leveled off near 56 days, as indicated by a quantitative DNA assay. Osteoblast/foam constructs with a low cell seeding density achieved comparable DNA content and alkaline phosphatase (ALPase) activity after 14 days, and mineralization results after 56 days to those with a high cell seeding density. A maximum penetration depth of osseous tissue of 220+/-40 microm was reached after 56 days in the osteoblast/foam constructs of 150-300 microm pore size initially seeded with a high cell density. For constructs of 500-710 microm pore size, the penetration depth was 190+/-40 microm under the same conditions. Scaffold pore size and thickness did not significantly affect the proliferation or function of osteoblasts as demonstrated by DNA content, ALPase activity, and mineralized tissue formation. These data show that comparable bone-like tissues can be engineered in vitro over a 56 day period using different rat calvarial osteoblast seeding densities onto biodegradable polymer scaffolds with pore sizes in the range of 150-710 microm. When compared with the results of a previous study where similar polymer scaffolds were seeded and cultured with marrow stromal cells, this study

Effect of polymer viscosity on physicochemical properties and ocular tolerance of FB-loaded PLGA nanospheres.

PubMed

Araújo, J; Vega, E; Lopes, C; Egea, M A; Garcia, M L; Souto, E B

2009-08-01

Poly(lactide-co-glycolide) acid (PLGA) nanospheres incorporating flurbiprofen (FB) were produced by the solvent displacement technique, for ocular applications aiming to avoid/minimize inflammation induced by surgical trauma. In this work, a PLGA of low viscosity has been tested and the results obtained were compared with those previously reported by Vega et al. The physicochemical properties of the developed formulations were evaluated by measuring particle size, zeta potential and FB entrapment efficiency, showing no significant differences. Release studies demonstrated that the formulation produced with PLGA of higher viscosity revealed a slower drug release rate. Stability analysis, for a period of 75 days, was performed using three complementary methods: (i) turbidity experiments using a Turbiscan optical analyzer, (ii) particle size measurements, and (iii) zeta potential analysis. The results revealed long-term physicochemical stability suitability for ophthalmic use, being independent from the polymer viscosity. The ocular tolerance was assessed by an alternative in vitro method to animal experimentation, the HET-CAM. For all developed formulations no ocular irritancy has been detected.

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

Release of a wound-healing agent from PLGA microspheres in a thermosensitive gel.

PubMed

Machado, H A; Abercrombie, J J; You, T; Deluca, P P; Leung, K P

2013-01-01

The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4-7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 μm. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant

In vivo testing of a biodegradable woven fabric made of bioactive glass fibers and PLGA80--a pilot study in the rabbit.

PubMed

Alm, Jessica J; Frantzén, Janek P A; Moritz, Niko; Lankinen, Petteri; Tukiainen, Mikko; Kellomäki, Minna; Aro, Hannu T

2010-05-01

The purpose of this study was to perform an intra-animal comparison of biodegradable woven fabrics made of bioactive glass (BG) fibers and poly(L-lactide-co-glycolide) 80/20 copolymer (PLGA(80)) fibers or PLGA(80) fibers alone, in surgical stabilization of bone graft. The BG fibers (BG 1-98) were aimed to enhance bone growth at site of bone grafting, whereas the PLGA component was intended to provide structural strength and flexibility to the fabric. Bone formation was analyzed qualitatively by histology and quantitatively by peripheral quantitative computed tomography (pQCT) at 12 weeks. The surgical handling properties of the control PLGA(80) fabric were more favorable. Both fabrics were integrated with the cortical bone surfaces, but BG fibers showed almost complete resorption. There were no signs of adverse local tissue reactions. As a proof of material integration and induced new bone formation, there was a significant increase in bone volume of the operated femurs compared with the contralateral intact bone (25% with BG/PLGA(80) fabric, p < 0.001 and 28% with the control PLGA(80) fabric, p = 0.006). This study failed to demonstrate the previously seen positive effect of BG 1-98 on osteogenesis, probably due to the changed resorption properties of BG in the form of fibers. Therefore, the feasibility and safety of BG as fibers needs to be reevaluated before use in clinical applications. (c) 2010 Wiley Periodicals, Inc.

Preparation and Imaging Investigation of Dual-targeted C3F8-filled PLGA Nanobubbles as a Novel Ultrasound Contrast Agent for Breast Cancer.

PubMed

Du, Jing; Li, Xiao-Yu; Hu, He; Xu, Li; Yang, Shi-Ping; Li, Feng-Hua

2018-03-01

Molecularly-targeted contrast enhanced ultrasound (US) imaging is a promising imaging strategy with large potential for improving diagnostic accuracy of conventional US imaging in breast cancer detection. Therefore, we constructed a novel dual-targeted nanosized US contrast agent (UCA) directed at both vascular endothelial growth factor receptor 2 (VEGFR2) and human epidermal growth factor receptor 2 (HER2) based on perfluoropropane (C 3 F 8 )-filled poly(lactic-co-glycolic acid) (PLGA) (NBs) for breast cancer detection. In vitro, single- or dual-targeted PLGA NBs showed high target specificities and better effects of target enhancement in VEGFR2 or HER2-positive cells. In vivo, US imaging signal in the murine breast cancer model was significantly higher (P < 0.01) for dual-targeted NBs than single-targeted and non-targeted NBs. Small animal fluorescence imaging further confirmed the special affinity of the dual-targeted nanosized contrast agent to both VEGFR2 and HER2. Immunofluorescence and immunohistochemistry staining confirmed the expressions of VEGFR2 and HER2 on tumor neovasculature and tumor cells of breast cancer. In conclusions, the feasibility of using dual-targeted PLGA NBs to enhance ultrasonic images is demonstrated in vitro and in vivo. This may be a promising approach to target biomarkers of breast cancer for two site-specific US molecular imaging.

Composition of PLGA and PEI/DNA nanoparticles improves ultrasound-mediated gene delivery in solid tumors in vivo.

PubMed

Chumakova, Olga V; Liopo, Anton V; Andreev, Valery G; Cicenaite, Inga; Evers, B Mark; Chakrabarty, Shilla; Pappas, Todd C; Esenaliev, Rinat O

2008-03-18

The goal of this study was to enhance gene delivery and tumor cell transfection in vivo by using a combination of ultrasonication with complex nanoparticles consisting of two types of nanoparticles: PEI/DNA beta-gal plasmid with highly positive zeta-potential and air-filled poly (lactic-co-glycolic acid) (PLGA) particles (with negative zeta-potential) manufactured in our laboratory. The PLGA/PEI/DNA nanoparticles were a colloid with positive zeta-potential and injected i.v. in nude mice with DU145 human prostate tumors. We found that the combination of PLGA/PEI/DNA nanoparticles with ultrasonication substantially enhanced tumor cell transfection in vivo. The overexpression of beta-gal gene was evaluated histochemically and by Western blot analysis. At least an 8-fold increase of the cell transfection efficacy was obtained in irradiated tumors compared to non-irradiated controls, while little to no cell death was produced by ultrasonication.

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

PubMed

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

2017-06-01

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

Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-11.

PubMed

Santos, Diego M; Carneiro, Marcia W; de Moura, Tatiana R; Fukutani, Kiyoshi; Clarencio, Jorge; Soto, Manuel; Espuelas, Socorro; Brodskyn, Claudia; Barral, Aldina; Barral-Netto, Manoel; de Oliveira, Camila I

2012-01-01

Vaccine development has been a priority in the fight against leishmaniases, which are vector-borne diseases caused by Leishmania protozoa. Among the different immunization strategies employed to date is inoculation of plasmid DNA coding for parasite antigens, which has a demonstrated ability to induce humoral and cellular immune responses. In this sense, inoculation of plasmid DNA encoding Leishmania kinetoplasmid membrane protein-11 (KMP-11) was able to confer protection against visceral leishmaniasis. However, recently the use of antigen delivery systems such as poly(lactic-co-glycolic acid) (PLGA) nanoparticles has also proven effective for eliciting protective immune responses. In the present work, we tested two immunization strategies with the goal of obtaining protection, in terms of lesion development and parasite load, against cutaneous leishmaniasis caused by L. braziliensis. One strategy involved immunization with plasmid DNA encoding L. infantum chagasi KMP-11. Alternatively, mice were primed with PLGA nanoparticles loaded with the recombinant plasmid DNA and boosted using PLGA nanoparticles loaded with recombinant KMP-11. Both immunization strategies elicited detectable cellular immune responses with the presence of both proinflammatory and anti-inflammatory cytokines; mice receiving the recombinant PLGA nanoparticle formulations also demonstrated anti-KMP-11 IgG1 and IgG2a. Mice were then challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development was not inhibited following either immunization strategy. However, immunization with PLGA nanoparticles resulted in a more prominent reduction in parasite load at the infection site when compared with immunization using plasmid DNA alone. This effect was associated with a local increase in interferon-gamma and in tumor necrosis factor-alpha. Both immunization strategies also resulted in a lower parasite load in the draining lymph nodes, albeit not significantly. Our results

A Novel High Mechanical Property PLGA Composite Matrix Loaded with Nanodiamond-Phospholipid Compound for Bone Tissue Engineering.

PubMed

Zhang, Fan; Song, Qingxin; Huang, Xuan; Li, Fengning; Wang, Kun; Tang, Yixing; Hou, Canglong; Shen, Hongxing

2016-01-20

A potential bone tissue engineering material was produced from a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), loaded with nanodiamond phospholipid compound (NDPC) via physical mixing. On the basis of hydrophobic effects and physical absorption, we modified the original hydrophilic surface of the nanodiamond (NDs) with phospholipids to be amphipathic, forming a typical core-shell structure. The ND-phospholipid weight ratio was optimized to generate sample NDPC50 (i.e., ND-phospholipid weight ratio of 100:50), and NDPC50 was able to be dispersed in a PLGA matrix at up to 20 wt %. Compared to a pure PLGA matrix, the introduction of 10 wt % of NDPC (i.e., sample NDPC50-PF10) resulted in a significant improvement in the material's mechanical and surface properties, including a decrease in the water contact angle from 80 to 55°, an approximately 100% increase in the Young's modulus, and an approximate 550% increase in hardness, thus closely resembling that of human cortical bone. As a novel matrix supporting human osteoblast (hFOB1.19) growth, NDPC50-PFs with different amounts of NDPC50 demonstrated no negative effects on cell proliferation and osteogenic differentiation. Furthermore, we focused on the behaviors of NDPC-PFs implanted into mice for 8 weeks and found that NDPC-PFs induced acceptable immune response and can reduce the rapid biodegradation of PLGA matrix. Our results represent the first in vivo research on ND (or NDPC) as nanofillers in a polymer matrix for bone tissue engineering. The high mechanical properties, good in vitro and in vivo biocompatibility, and increased mineralization capability suggest that biodegradable PLGA composite matrices loaded with NDPC may potentially be useful for a variety of biomedical applications, especially bone tissue engineering.

Luminescent/magnetic PLGA-based hybrid nanocomposites: a smart nanocarrier system for targeted codelivery and dual-modality imaging in cancer theranostics.

PubMed

Shen, Xue; Li, Tingting; Chen, Zhongyuan; Geng, Yue; Xie, Xiaoxue; Li, Shun; Yang, Hong; Wu, Chunhui; Liu, Yiyao

2017-01-01

Cancer diagnosis and treatment represent an urgent medical need given the rising cancer incidence over the past few decades. Cancer theranostics, namely, the combination of diagnostics and therapeutics within a single agent, are being developed using various anticancer drug-, siRNA-, or inorganic materials-loaded nanocarriers. Herein, we demonstrate a strategy of encapsulating quantum dots, superparamagnetic Fe 3 O 4 nanocrystals, and doxorubicin (DOX) into biodegradable poly(d,l-lactic- co -glycolic acid) (PLGA) polymeric nanocomposites using the double emulsion solvent evaporation method, followed by coupling to the amine group of polyethyleneimine premodified with polyethylene glycol-folic acid (PEI-PEG-FA [PPF]) segments and adsorption of vascular endothelial growth factor (VEGF)-targeted small hairpin RNA (shRNA). VEGF is important for tumor growth, progression, and metastasis. These drug-loaded luminescent/magnetic PLGA-based hybrid nanocomposites (LDM-PLGA/PPF/VEGF shRNA) were fabricated for tumor-specific targeting, drug/gene delivery, and cancer imaging. The data showed that LDM-PLGA/PPF/VEGF shRNA nanocomposites can codeliver DOX and VEGF shRNA into tumor cells and effectively suppress VEGF expression, exhibiting remarkable synergistic antitumor effects both in vitro and in vivo. The cell viability waŝ14% when treated with LDM-PLGA/PPF/VEGF shRNA nanocomposites ([DOX] =25 μg/mL), and in vivo tumor growth data showed that the tumor volume decreased by 81% compared with the saline group at 21 days postinjection. Magnetic resonance and fluorescence imaging data revealed that the luminescent/magnetic hybrid nanocomposites may also be used as an efficient nanoprobe for enhanced T 2 -weighted magnetic resonance and fluorescence imaging in vitro and in vivo. The present work validates the great potential of the developed multifunctional LDM-PLGA/PPF/VEGF shRNA nanocomposites as effective theranostic agents through the codelivery of drugs/genes and dual

Luminescent/magnetic PLGA-based hybrid nanocomposites: a smart nanocarrier system for targeted codelivery and dual-modality imaging in cancer theranostics

PubMed Central

Shen, Xue; Li, Tingting; Chen, Zhongyuan; Geng, Yue; Xie, Xiaoxue; Li, Shun; Yang, Hong; Wu, Chunhui; Liu, Yiyao

2017-01-01

Cancer diagnosis and treatment represent an urgent medical need given the rising cancer incidence over the past few decades. Cancer theranostics, namely, the combination of diagnostics and therapeutics within a single agent, are being developed using various anticancer drug-, siRNA-, or inorganic materials-loaded nanocarriers. Herein, we demonstrate a strategy of encapsulating quantum dots, superparamagnetic Fe3O4 nanocrystals, and doxorubicin (DOX) into biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) polymeric nanocomposites using the double emulsion solvent evaporation method, followed by coupling to the amine group of polyethyleneimine premodified with polyethylene glycol-folic acid (PEI-PEG-FA [PPF]) segments and adsorption of vascular endothelial growth factor (VEGF)-targeted small hairpin RNA (shRNA). VEGF is important for tumor growth, progression, and metastasis. These drug-loaded luminescent/magnetic PLGA-based hybrid nanocomposites (LDM-PLGA/PPF/VEGF shRNA) were fabricated for tumor-specific targeting, drug/gene delivery, and cancer imaging. The data showed that LDM-PLGA/PPF/VEGF shRNA nanocomposites can codeliver DOX and VEGF shRNA into tumor cells and effectively suppress VEGF expression, exhibiting remarkable synergistic antitumor effects both in vitro and in vivo. The cell viability waŝ14% when treated with LDM-PLGA/PPF/VEGF shRNA nanocomposites ([DOX] =25 μg/mL), and in vivo tumor growth data showed that the tumor volume decreased by 81% compared with the saline group at 21 days postinjection. Magnetic resonance and fluorescence imaging data revealed that the luminescent/magnetic hybrid nanocomposites may also be used as an efficient nanoprobe for enhanced T2-weighted magnetic resonance and fluorescence imaging in vitro and in vivo. The present work validates the great potential of the developed multifunctional LDM-PLGA/PPF/VEGF shRNA nanocomposites as effective theranostic agents through the codelivery of drugs/genes and dual

Impact of surfactants on the target recognition of Fab-conjugated PLGA nanoparticles.

PubMed

Kennedy, Patrick J; Perreira, Ines; Ferreira, Daniel; Nestor, Marika; Oliveira, Carla; Granja, Pedro L; Sarmento, Bruno

2018-06-01

Targeted drug delivery with nanoparticles (NPs) requires proper surface ligand presentation and availability. Surfactants are often used as stabilizers in the production of targeted NPs. Here, we evaluated the impact of surfactants on ligand functionalization and downstream molecular recognition. Our model system consisted of fluorescent poly(lactic-co-glycolic acid) (PLGA) NPs that were nanoprecipitated in one of a small panel of commonly-used surfactants followed by equivalent washes and conjugation of an engineered Fab antibody fragment. Size, polydispersity index and zeta potential were determined by dynamic light scattering and laser Doppler anemometry, and Fab presence on the NPs was assessed by enzyme-linked immunosorbent assay. Most importantly, Fab-decorated NP binding to the cell surface receptor was monitored by fluorescence-activated cell sorting. 2% polyvinyl alcohol, 1% sodium cholate, 0.5% Pluronic F127 (F127) and 2% Tween-80 were initially tested. Of the four surfactants tested, PLGA NPs in 0.5% F127 and 2% Tween-80 had the highest cell binding. These two surfactants were then retested in two different concentrations, 0.5% and 2%. The Fab-decorated PLGA NPs in 2% F127 had the highest cell binding. This study highlights the impact of common surfactants and their concentrations on the downstream targeting of ligand-decorated NPs. Similar principles should be applied in the development of future targeted nanosystems where surfactants are employed. Copyright © 2018 Elsevier B.V. All rights reserved.

Osteoconductive Potential of Barrier NanoSiO2 PLGA Membranes Functionalized by Plasma Enhanced Chemical Vapour Deposition

PubMed Central

Terriza, Antonia; Vilches-Pérez, Jose I.; de la Orden, Emilio; Yubero, Francisco; Gonzalez-Caballero, Juan L.; González-Elipe, Agustin R.; Vilches, José; Salido, Mercedes

2014-01-01

The possibility of tailoring membrane surfaces with osteoconductive potential, in particular in biodegradable devices, to create modified biomaterials that stimulate osteoblast response should make them more suitable for clinical use, hopefully enhancing bone regeneration. Bioactive inorganic materials, such as silica, have been suggested to improve the bioactivity of synthetic biopolymers. An in vitro study on HOB human osteoblasts was performed to assess biocompatibility and bioactivity of SiO2 functionalized poly(lactide-co-glycolide) (PLGA) membranes, prior to clinical use. A 15 nm SiO2 layer was deposited by plasma enhanced chemical vapour deposition (PECVD), onto a resorbable PLGA membrane. Samples were characterized by X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy, and infrared spectroscopy (FT-IR). HOB cells were seeded on sterilized test surfaces where cell morphology, spreading, actin cytoskeletal organization, and focal adhesion expression were assessed. As proved by the FT-IR analysis of samples, the deposition by PECVD of the SiO2 onto the PLGA membrane did not alter the composition and other characteristics of the organic membrane. A temporal and spatial reorganization of cytoskeleton and focal adhesions and morphological changes in response to SiO2 nanolayer were identified in our model. The novedous SiO2 deposition method is compatible with the standard sterilization protocols and reveals as a valuable tool to increase bioactivity of resorbable PLGA membranes. PMID:24883304

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.

A novel therapy strategy for bile duct repair using tissue engineering technique: PCL/PLGA bilayered scaffold with hMSCs.

PubMed

Zong, Chen; Wang, Meicong; Yang, Fuchun; Chen, Guojun; Chen, Jiarong; Tang, Zihua; Liu, Quanwen; Gao, Changyou; Ma, Lie; Wang, Jinfu

2017-04-01

The current clinical treatments for complications caused by hepatobiliary surgery still have some inevitable weakness. The aim of the study was to fabricate a tissue-engineered bile duct that utilized a novel bilayered polymer scaffold combined with human bone marrow-derived mesenchymal stem cells (hMSCs) for new treatment of biliary disease. The biocompatibility of polycaprolactone (PCL) (PCL)/poly(lactide-co-glycolide) (PLGA) scaffold with hMSCs was first examined, and the hMSC-PCL/PLGA constructs (MPPCs) prepared. The MPPCs and blank scaffolds were then transplanted into 18 pigs for evaluation its efficacy on bile duct repairing, respectively. In vitro, the PCL/PLGA scaffold was verified to support the adhesion, proliferation and matrix deposition of hMSCs. There was no sign of bile duct narrowing and cholestasis in all experimental animals. At 6 months, the MPPCs had a superior repairing effect on the bile duct injury, compared with the blank PCL/PLGA scaffolds. Therefore, the implanted scaffolds could not only support the biliary tract and allow free bile flow but also had direct or indirect positive effects on repair of injured bile duct. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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

Response of human dental pulp cells to a silver-containing PLGA/TCP-nanofabric as a potential antibacterial regenerative pulp-capping material.

PubMed

Cvikl, Barbara; Hess, Samuel C; Miron, Richard J; Agis, Hermann; Bosshardt, Dieter; Attin, Thomas; Schmidlin, Patrick R; Lussi, Adrian

2017-02-27

Damage or exposure of the dental pulp requires immediate therapeutic intervention. This study assessed the biocompatibility of a silver-containing PLGA/TCP-nanofabric scaffold (PLGA/Ag-TCP) in two in vitro models, i.e. the material adapted on pre-cultured cells and cells directly cultured on the material, respectively. Collagen saffolds with and without hyaluronan acid (Coll-HA; Coll) using both cell culturing methods and cells growing on culture plates served as reference. Cell viability and proliferation were assessed after 24, 48, and 72 h based on formazan formation and BrdU incorporation. Scaffolds were harvested. Gene expression of interleukin(IL)-6, tumor necrosis factor (TNF)-alpha, and alkaline phosphatase (AP) was assessed 24 h after stimulation. In both models formazan formation and BrdU incorporation was reduced by PLGA/Ag-TCP on dental pulp cells, while no significant reduction was found in cells with Coll and Coll-HA. Cells with PLGA/Ag-TCP for 72 h showed similar relative BrdU incorporation than cells stimulated with Coll and Coll-HA. A prominent increase in the pro-inflammatory genes IL-6 and TNF-α was observed when cells were cultured with PLGA/Ag-TCP compared to the other groups. This increase was parallel with a slight increase in AP expression. Overall, no differences between the two culture methods were observed. PLGA/Ag-TCP decreased viability and proliferation rate of human dental pulp cells and increased the pro-inflammatory capacity and alkaline phosphatase expression. Whether these cellular responses observed in vitro translate into pulp regeneration in vivo will be assessed in further studies.

Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats.

PubMed

Peters, Tobias; Kim, Seong-Woo; Castro, Vinicius; Stingl, Krunoslav; Strasser, Torsten; Bolz, Sylvia; Schraermeyer, Ulrich; Mihov, George; Zong, MengMeng; Andres-Guerrero, Vanessa; Herrero Vanrell, Rocio; Dias, Aylvin A; Cameron, Neil R; Zrenner, Eberhart

2017-04-01

To study the suitability of injectable microspheres based on poly(ester amide) (PEA) or poly lactic-co-glycolic acid (PLGA) as potential vehicles for intravitreal drug delivery in rat eyes. Dexamethasone-loaded PEA microspheres (PEA + DEX) were also evaluated. Forty male Sprague Dawley rats were divided into four groups that received different intravitreally injected microspheres: PEA group (n = 12); PLGA group (n = 12); PEA + DEX group (n = 8); and control group (no injection, n = 8). Electroretinography (ERG), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (sdOCT) were performed at baseline, weeks 1 and 2, and months 1, 2, and 3 after intravitreal injection. Eyes were histologically examined using light microscopy and transmission electron microscopy at the end of the in vivo study. There were no statistically significant changes in ERG among the groups. Abnormal FAF pattern and abnormal deposits in OCT were observed after injection but almost completely disappeared between week 2 and month 3 in all injected groups. GFAP staining showed that Müller glia cell activation was most pronounced in PLGA-injected eyes. Increased cell death was not observed by TUNEL staining at month 1. In electron microscopy at month 3, the remnants of microparticles were found in the retinal cells of all injected groups, and loss of plasma membrane was seen in the PLGA group. Although morphological changes such as mild glial activation and material remnants were observed histologically 1 month and 3 months after injection in all injected groups, minor cell damage was noted only in the PLGA group at 3 months after injection. No evidence of functional abnormality relative to untreated eyes could be detected by ERG 3 months after injection in all groups. Changes observed in in vivo imaging such as OCT and FAF disappeared after 3 months in almost all cases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of facile drug delivery platform of ranibizumab fabricated PLGA-PEGylated magnetic nanoparticles for age-related macular degeneration therapy.

PubMed

Yan, Jian; Peng, Xifeng; Cai, Yulian; Cong, Wendong

2018-06-01

The present anti-angiogenic therapies for neovascular age-related macular degeneration require effective drug delivery systems for transfer drug molecules. Ranibizumab is an active humanized monoclonal antibody that counteracts active forms of vascular endothelial growth factor A in the neovascular age-related macular degeneration therapy. The development of ranibizumab-related therapies, we have designed the effective drug career with engineered magnetic nanoparticles (Fe 3 O 4 ) as a facile platform of ranibizumab delivery for the treatment of neovascular age-related macular degeneration. Ranibizumab conjugated iron oxide (Fe 3 O 4 )/PEGylated poly lactide-co-glycolide (PEG-PLGA) was successfully designed and the synthesized materials are analyzed different analytical techniques. The microscopic techniques (Scanning Electron Microscopy (SEM) & Transmission Electron Microscopy (TEM)) are clearly displayed that spherical nanoparticles into the PEG-PLGA matrix and presence of elements and chemical interactions confirmed by the results of energy dispersive X-ray analysis (EDX) and Fourier trans-form infrared (FTIR) spectroscopic methods. The in vitro anti-angiogenic evaluation of Fe 3 O 4 /PEG-PLGA polymer nanomaterial efficiently inhibits the tube formation in the Matrigel-based assay method by using human umbilical vein endothelial cells. Ranibizumab treated Fe 3 O 4 /PEG-PLGA polymer nanomaterials not disturbed cell proliferation and the results could not display the any significant differences in human endothelial cells. The present investigated results describe that Fe 3 O 4 /PEG-PLGA polymer nanomaterials can be highly favorable and novel formulation for the treatment of neovascular age-related macular degeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

Ferritin Decorated PLGA/Paclitaxel Loaded Nanoparticles Endowed with an Enhanced Toxicity Toward MCF-7 Breast Tumor Cells.

PubMed

Turino, Ludmila N; Ruggiero, Maria R; Stefanìa, Rachele; Cutrin, Juan C; Aime, Silvio; Geninatti Crich, Simonetta

2017-04-19

Polylactic and glycolic acid nanoparticles (PLGA-NPs), coated with L-ferritin, are exploited for the simultaneous delivery of paclitaxel and an amphiphilic Gd based MRI contrast agent into breast cancer cells (MCF7). L-ferritin has been covalently conjugated to the external surface of PLGA-NPs exploiting NHS activated carboxylic groups. The results confirmed that nanoparticles decorated with L-ferritin have many advantages with respect to both albumin-decorated and nondecorated particles. Ferritin moieties endow PLGA-NPs with targeting capability, exploiting SCARA5 receptors overexpressed by these tumor cells, that results in an increased paclitaxel cytotoxicity. Moreover, protein coating increased nanoparticle stability, thus reducing the fast and aspecific drug release before reaching the target. The theranostic potential of the nanoparticles has been demonstrated by evaluating the signal intensity enhancement on T 1 -weighted MRI images of labeled MCF7 cells. The results were compared with that obtained with MDA cells used as negative control due to their lower SCARA5 expression.

PLGA nanoparticles modified with a BBB-penetrating peptide co-delivering Aβ generation inhibitor and curcumin attenuate memory deficits and neuropathology in Alzheimer's disease mice.

PubMed

Huang, Na; Lu, Shuai; Liu, Xiao-Ge; Zhu, Jie; Wang, Yu-Jiong; Liu, Rui-Tian

2017-10-06

Alzheimer's disease (AD) is the most common form of dementia, characterized by the formation of extracellular senile plaques and neuronal loss caused by amyloid β (Aβ) aggregates in the brains of AD patients. Conventional strategies failed to treat AD in clinical trials, partly due to the poor solubility, low bioavailability and ineffectiveness of the tested drugs to cross the blood-brain barrier (BBB). Moreover, AD is a complex, multifactorial neurodegenerative disease; one-target strategies may be insufficient to prevent the processes of AD. Here, we designed novel kind of poly(lactide-co-glycolic acid) (PLGA) nanoparticles by loading with Aβ generation inhibitor S1 (PQVGHL peptide) and curcumin to target the detrimental factors in AD development and by conjugating with brain targeting peptide CRT (cyclic CRTIGPSVC peptide), an iron-mimic peptide that targets transferrin receptor (TfR), to improve BBB penetration. The average particle size of drug-loaded PLGA nanoparticles and CRT-conjugated PLGA nanoparticles were 128.6 nm and 139.8 nm, respectively. The results of Y-maze and new object recognition test demonstrated that our PLGA nanoparticles significantly improved the spatial memory and recognition in transgenic AD mice. Moreover, PLGA nanoparticles remarkably decreased the level of Aβ, reactive oxygen species (ROS), TNF-α and IL-6, and enhanced the activities of super oxide dismutase (SOD) and synapse numbers in the AD mouse brains. Compared with other PLGA nanoparticles, CRT peptide modified-PLGA nanoparticles co-delivering S1 and curcumin exhibited most beneficial effect on the treatment of AD mice, suggesting that conjugated CRT peptide, and encapsulated S1 and curcumin exerted their corresponding functions for the treatment.

40 CFR 761.267 - Sampling non-porous surfaces.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Sampling non-porous surfaces. 761.267... PROHIBITIONS Cleanup Site Characterization Sampling for PCB Remediation Waste in Accordance with § 761.61(a)(2) § 761.267 Sampling non-porous surfaces. (a) Sample large, nearly flat, non-porous surfaces by dividing...

40 CFR 761.267 - Sampling non-porous surfaces.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Sampling non-porous surfaces. 761.267... PROHIBITIONS Cleanup Site Characterization Sampling for PCB Remediation Waste in Accordance with § 761.61(a)(2) § 761.267 Sampling non-porous surfaces. (a) Sample large, nearly flat, non-porous surfaces by dividing...

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.

Comparative evaluation of PLGA nanoparticle delivery system for 5-fluorouracil and curcumin on squamous cell carcinoma.

PubMed

Masloub, Shaimaa M; Elmalahy, Mohamed H; Sabry, Dina; Mohamed, Wael S; Ahmed, Sahar H

2016-04-01

The purpose of this study is to assess the effect of 5-fluorouracil nanoparticles and curcumin naoparticles on cell proliferation and the expression of the apoptotic marker (caspase 3) in squamous cell carcinoma cell line. PLGA 5-fluorouracil nanopartciles and PLGA curcumin nanoparticles were prepared and applied for 24 and 48h on human laryngeal squamous carcinoma cell line (Hep-2) as regard IC 50 concentration. MTT assay was used for evaluation of cytotoxicity of prepared nanoparticles. Quantitaive reverse transcriptase polymerase chain reaction (QRT-PCR) was used for the assessment of caspase-3 expression in the treated cell line. The drug release rate profiles was dependent upon polymer to drug ratio, noting that the higher PLGA polymer ratio to 5-fluprouracil or curcumin drug showed faster release rates. On the other hand, the least PLGA polymer ratio to 5-fluprouracil or curcumin drug showed the slowest release rates. MTT assay revelaed that 5-fluorouracil nanoparticels or curcumin nanoparticels showed a clear cytotoxic effect on Hep-2 cell line compared to non treated cancer cells. The RT-PCR assessment of caspase-3 expression revealed that there was a significant increase in caspase-3 expression in Hep-2 cell line treated with 5-fluorouracil nanoparticles or curcumin compared to non treated cancer cells. Curcumin nanoparticles could be more active in inducing apoptosis in short term assays (24h) than long term assays (48h) due to differential cellular uptake. While 5-fluorouracil nanoparticles induced higher significant apoptosis in long term (48h) compared to curcumin group. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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

PubMed

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

2016-07-02

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

Evaluation of 3D printed PCL/PLGA/β-TCP versus collagen membranes for guided bone regeneration in a beagle implant model.

PubMed

Won, J-Y; Park, C-Y; Bae, J-H; Ahn, G; Kim, C; Lim, D-H; Cho, D-W; Yun, W-S; Shim, J-H; Huh, J-B

2016-10-07

Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PCL/PLGA/β-TCP) membranes with the widely used collagen membranes for guided bone regeneration (GBR) in beagle implant models. For mechanical property comparison in dry and wet conditions and cytocompatibility determination, we analyzed the rate and pattern of cell proliferation of seeded fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning electron microscopy. Osteogenic differentiation was verified using alizarin red S staining. At 8 weeks following implantation in vivo using beagle dogs, computed tomography and histological analyses were performed after sacrifice. Cell proliferation rates in vitro indicated that early cell attachment was higher in collagen than in PCL/PLGA/β-TCP membranes; however, the difference subsided by day 7. Similar outcomes were found for osteogenic differentiation, with approximately 2.5 times greater staining in collagen than PCL/PLGA/β-TCP, but without significant difference by day 14. In vivo, bone regeneration in the defect area, represented by new bone formation and bone-to-implant contact, paralleled those associated with collagen membranes. However, tensile testing revealed that whereas the PCL/PLGA/β-TCP membrane mechanical properties were conserved in both wet and dry states, the tensile property of collagen was reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo that PCL/PLGA/β-TCP membranes have similar levels of biocompatibility and bone regeneration as collagen membranes. In particular, considering that GBR is always applied to a wet environment (e.g. blood, saliva), we demonstrated that PCL/PLGA/β-TCP membranes maintained their form more reliably than collagen membranes in a wet setting, confirming their appropriateness as a GBR membrane.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo

NASA Astrophysics Data System (ADS)

Liu, Hui; Lv, Peizhen; Zhu, Yongjia; Wu, Huayu; Zhang, Kun; Xu, Fuben; Zheng, Li; Zhao, Jinmin

2017-01-01

Salidriside (SDS), a phenylpropanoid glycoside derived from Rhodiola rosea L, has been shown to be neuroprotective in many studies, which may be promising in nerve recovery. In this study, the neuroprotective effects of SDS on engineered nerve constructed by Schwann cells (SCs) and Poly (lactic-co-glycolic acid) (PLGA) were studied in vitro. We further investigated the effect of combinational therapy of SDS and PLGA/SCs based tissue engineering on peripheral nerve regeneration based on the rat model of nerve injury by sciatic transection. The results showed that SDS dramatically enhanced the proliferation and function of SCs. The underlying mechanism may be that SDS affects SCs growth through the modulation of neurotrophic factors (BDNF, GDNF and CNTF). 12 weeks after implantation with a 12 mm gap of sciatic nerve injury, SDS-PLGA/SCs achieved satisfying outcomes of nerve regeneration, as evidenced by morphological and functional improvements upon therapy by SDS, PLGA/SCs or direct suture group assessed by sciatic function index, nerve conduction assay, HE staining and immunohistochemical analysis. Our results demonstrated the significant role of introducing SDS into neural tissue engineering to promote nerve regeneration.

Anti-infective efficacy, cytocompatibility and biocompatibility of a 3D-printed osteoconductive composite scaffold functionalized with quaternized chitosan.

PubMed

Yang, Ying; Yang, Shengbing; Wang, Yugang; Yu, Zhifeng; Ao, Haiyong; Zhang, Hongbo; Qin, Ling; Guillaume, Olivier; Eglin, David; Richards, R Geoff; Tang, Tingting

2016-12-01

Contaminated or infected bone defects remain serious challenges in clinical trauma and orthopaedics, and a bone substitute with both osteoconductivity and antibacterial properties represents an improvement for treatment strategy. In this study, quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) was grafted to 3D-printed scaffolds composed of polylactide-co-glycolide (PLGA) and hydroxyapatite (HA), in order to design bone engineering scaffolds endowed with antibacterial and osteoconductive properties. We found that both the PLGA/HA/HACC and PLGA/HACC composite scaffolds decreased bacterial adhesion and biofilm formation under in vitro and in vivo conditions. Additionally, ATP leakage assay indicated that immobilizing HACC on the scaffolds could effectively disrupt microbial membranes. Using human bone marrow-derived mesenchymal stem cells (hBMSCs), we demonstrated that HA incorporated scaffolds, including PLGA/HA and PLGA/HA/HACC, favoured cell attachment, proliferation, spreading and osteogenic differentiation compared to HA-free PLGA or PLGA/HACC scaffolds. Finally, an in vivo biocompatibility assay conducted on rats, showed that HA incorporated scaffolds (including PLGA/HA and PLGA/HA/HACC scaffolds) exhibited good neovascularization and tissue integration. Taken together, our findings support the approach for developing porous PLGA/HA/HACC composite scaffold with potential clinical application in the treatment of infected bone. Although plenty of conductive scaffold biomaterials have been exploited to improve bone regeneration under infection, potential tissue toxicity under high concentration and antibiotic-resistance are their main deficiencies. This study indicated that HACC-grafted PLGA/HA composite scaffold prepared using an innovative 3D-printing technique and covalent grafting strategy showed significantly enhanced antibacterial activities, especially against the antibiotic-resistant strains, together with good osteogenic

Chaotic dynamics of large-scale double-diffusive convection in a porous medium

NASA Astrophysics Data System (ADS)

Kondo, Shutaro; Gotoda, Hiroshi; Miyano, Takaya; Tokuda, Isao T.

2018-02-01

We have studied chaotic dynamics of large-scale double-diffusive convection of a viscoelastic fluid in a porous medium from the viewpoint of dynamical systems theory. A fifth-order nonlinear dynamical system modeling the double-diffusive convection is theoretically obtained by incorporating the Darcy-Brinkman equation into transport equations through a physical dimensionless parameter representing porosity. We clearly show that the chaotic convective motion becomes much more complicated with increasing porosity. The degree of dynamic instability during chaotic convective motion is quantified by two important measures: the network entropy of the degree distribution in the horizontal visibility graph and the Kaplan-Yorke dimension in terms of Lyapunov exponents. We also present an interesting on-off intermittent phenomenon in the probability distribution of time intervals exhibiting nearly complete synchronization.

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.

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. © 2011 American Chemical Society

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

MAPs/bFGF-PLGA microsphere composite-coated titanium surfaces promote increased adhesion and proliferation of fibroblasts.

PubMed

Wang, Zhongshan; Wu, Guofeng; Bai, Shizhu; Feng, Zhihong; Dong, Yan; Zhou, Jian; Qin, Haiyan; Zhao, Yimin

2014-06-01

Infection and epithelial downgrowth are two major problems with maxillofacial transcutaneous implants, and both are mainly due to lack of stable closure of soft tissues at transcutaneous sites. Fibroblasts have been shown to play a key role in the formation of biological seals. In this work, titanium (Ti) model surfaces were coated with mussel adhesive proteins (MAPs) utilizing its unique adhesion ability on diverse inorganic and organic surfaces in wet environments. Prepared basic fibroblast growth factor (bFGF)-poly(lactic-co-glycolic acid) (PLGA) microspheres can be easily synthesized and combined onto MAPs-coated Ti surfaces, due to the negative surface charges of microspheres in aqueous solution, which is in contrast to the positive charges of MAPs. Titanium model surfaces were divided into three groups. Group A: MAPs/bFGF-PLGA microspheres composite-coated Ti surfaces. Group B: MAPs-coated Ti surfaces. Group C: uncoated Ti surfaces. The effects of coated Ti surfaces on adhesion of fibroblasts, cytoskeletal organization, proliferation, and extracellular matrix (ECM)-related gene expressions were examined. The results revealed increased adhesion (P < 0.05), enhanced actin cytoskeletal organization, and up-regulated ECM-related gene expressions in groups A and B compared with group C. Increased proliferation of fibroblasts during five days of incubation was observed in group A compared with groups B and C (P < 0.05). Collectively, the results from this in vitro study demonstrated that MAPs/bFGF-PLGA microspheres composite-coated Ti surfaces had the ability to increase fibroblast functionality. In addition, MAPs/bFGF-PLGA microsphere composite-coated Ti surfaces should be studied further as a method of promoting formation of stable biological seals around transcutaneous sites.

Evaluation of Motor Neuron-Like Cell Differentiation of hEnSCs on Biodegradable PLGA Nanofiber Scaffolds.

PubMed

Ebrahimi-Barough, Somayeh; Norouzi Javidan, Abbas; Saberi, Hoshangh; Joghataei, Mohammad Tghi; Rahbarghazi, Reza; Mirzaei, Esmaeil; Faghihi, Faezeh; Shirian, Sadegh; Ai, Armin; Ai, Jafar

2015-12-01

Human endometrium is a high-dynamic tissue that contains human endometrial stem cells (hEnSCs) which can be differentiated into a number of cell lineages. The differentiation of hEnSCs into many cell lineages such as osteoblast, adipocyte, and neural cells has been investigated previously. However, the differentiation of these stem cells into motor neuron-like cells has not been investigated yet. Different biochemical and topographical cues can affect the differentiation of stem cells into a specific cell. The aim of this study was to investigate the capability of hEnSCs to be differentiated into motor neuron-like cells under biochemical and topographical cues. The biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) electrospun nanofibrous scaffold was used as a topographical cue. Human EnSCs were cultured on the PLGA scaffold and tissue culture polystyrene (TCP), then differentiation of hEnSCs into motor neuron-like cells under induction media including retinoic acid (RA) and sonic hedgehog (Shh) were evaluated for 15 days. The proliferation rate of cells was assayed by using MTT assay. The morphology of cells was studied by scanning electron microscopy imaging, and the expression of motor neuron-specific markers by real-time PCR and immunocytochemistry. Results showed that survival and differentiation of hEnSCs into motor neuron-like cells on the PLGA scaffold were better than those on the TCP group. Taken together, the results suggest that differentiated hEnSCs on PLGA can provide a suitable, three-dimensional situation for neuronal survival and outgrowth for regeneration of the central nervous system, and these cells may be a potential candidate in cellular therapy for motor neuron diseases.

Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells.

PubMed

Waghela, Bhargav N; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy.

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.

Parallel Large-Scale Molecular Dynamics Simulation Opens New Perspective to Clarify the Effect of a Porous Structure on the Sintering Process of Ni/YSZ Multiparticles.

PubMed

Xu, Jingxiang; Higuchi, Yuji; Ozawa, Nobuki; Sato, Kazuhisa; Hashida, Toshiyuki; Kubo, Momoji

2017-09-20

Ni sintering in the Ni/YSZ porous anode of a solid oxide fuel cell changes the porous structure, leading to degradation. Preventing sintering and degradation during operation is a great challenge. Usually, a sintering molecular dynamics (MD) simulation model consisting of two particles on a substrate is used; however, the model cannot reflect the porous structure effect on sintering. In our previous study, a multi-nanoparticle sintering modeling method with tens of thousands of atoms revealed the effect of the particle framework and porosity on sintering. However, the method cannot reveal the effect of the particle size on sintering and the effect of sintering on the change in the porous structure. In the present study, we report a strategy to reveal them in the porous structure by using our multi-nanoparticle modeling method and a parallel large-scale multimillion-atom MD simulator. We used this method to investigate the effect of YSZ particle size and tortuosity on sintering and degradation in the Ni/YSZ anodes. Our parallel large-scale MD simulation showed that the sintering degree decreased as the YSZ particle size decreased. The gas fuel diffusion path, which reflects the overpotential, was blocked by pore coalescence during sintering. The degradation of gas diffusion performance increased as the YSZ particle size increased. Furthermore, the gas diffusion performance was quantified by a tortuosity parameter and an optimal YSZ particle size, which is equal to that of Ni, was found for good diffusion after sintering. These findings cannot be obtained by previous MD sintering studies with tens of thousands of atoms. The present parallel large-scale multimillion-atom MD simulation makes it possible to clarify the effects of the particle size and tortuosity on sintering and degradation.

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

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

PubMed

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

Enteric-coated capsules filled with mono-disperse micro-particles containing PLGA-lipid-PEG nanoparticles for oral delivery of insulin.

PubMed

Yu, Fei; Li, Yang; Liu, Chang Sheng; Chen, Qin; Wang, Gui Huan; Guo, Wei; Wu, Xue E; Li, Dong Hui; Wu, Winston Duo; Chen, Xiao Dong

2015-04-30

The success of the oral delivery of insulin (INS) as a therapeutic protein drug would significantly improve the quality of life of diabetic patients who would otherwise receive multiple daily INS injections. The oral delivery of INS, however, is still limited in its delivery efficiency, which could be due to the chemical, enzymatic, and adsorption barriers. In this work, in an attempt to improve the delivery efficiency, the INS-loaded polymer-lipid hybrid nanoparticles (INS-PLGA-lipid-PEG NPs) were designed and constructed through a double-emulsion solvent evaporation technique, followed by formulation of the spherical micro-particles using a spray freeze dryer (SFD). This kind of dryers has a uniquely designed microfluidic aerosol nozzle (MFAN), ensuring the formation of uniform particles. The resulted particles of ∼212 μm could easily be reverted to discrete INS-PLGA-lipid-PEG NPs in an aqueous solution. The INS-PLGA-lipid-PEG NPs created in this work showed a highly negative surface charge, excellent entrapment efficiency (92.3%) and a sustained drug release (∼24 h). Confocal laser scanning microscopy and flow cytometer were used to show that the cellular uptake efficiency for the INS-PLGA-lipid-PEG NPs was more effective than the INS in Caco-2 cells. More importantly, the in vivo pharmacodynamics demonstrated that the orally delivered system induced a prolonged decrease in blood glucose levels among diabetic rats. The relative bioavailability of INS compared with subcutaneous injection in diabetic rats was found to be approximately 12%. These results suggested that the encapsulated INS-PLGA-lipid-PEG NPs are promising and should be investigated further in the near future as an effective INS oral delivery system. Copyright © 2015. Published by Elsevier B.V.

Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus.

PubMed

Liu, Xiangwei; Tan, Naiwen; Zhou, Yuchao; Wei, Hongbo; Ren, Shuai; Yu, Fan; Chen, Hui; Jia, Chengming; Yang, Guodong; Song, Yingliang

2017-01-01

Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs) of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204) and dispersed them in the poly(lactic-co-glycolic acid) (PLGA) solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT) reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient osseointegation in diabetes mellitus, while PLGA sheets aided the release of AuNP-antagomiR204, which would be a promising strategy for titanium implant surface functionalization toward better osseointegration.

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.

Modification of TiO(2) nanotube surfaces by electro-spray deposition of amoxicillin combined with PLGA for bactericidal effects at surgical implantation sites.

PubMed

Lee, Jung-Hwan; Moon, Seung-Kyun; Kim, Kwang-Mahn; Kim, Kyoung-Nam

2013-01-01

To fabricate the antibiotic-releasing coatings on TiO(2) nanotube surfaces for wide applications of implant and bone plate in medical and dental surgery, the optimal deposition time of amoxicillin/PLGA solution simultaneously performing non-toxicity and a high bactericidal effect for preventing early implant failures was found. FE-SEM, ESD and FT-IR were used for confirming deposition of amoxicillin/PLGA on the TiO(2) surface. Also, the elution of amoxicillin/PLGA in a TiO(2) nanotube surface was measured by a UV-VIS spectrophotometer. The bactericidal effect of amoxicillin on the TiO(2) nanotube surface was evaluated by using Staphylococcus aureus (S. aureus). The cytotoxicity and cell proliferation were observed by WST assay using MC3T3-E1 osteoblast cells. The results indicated that the TiO(2) nanotube surface controlled by electro-spray deposition time with amoxicillin/PLGA solution could provide a high bactericidal effect against S. aureus by the bactericidal effect of amoxicillin, as well as good osteoblast cell proliferation at the TiO(2) nanotube surface without toxicity. This study used electro-spray deposition (ESD) methodology to obtain amoxicillin deposition in nanotube structures of TiO(2) and found the optimal deposition time of amoxicillin/PLGA solution simultaneously performing non-toxicity and a high bactericidal effect for preventing early implant failures.

Fabrication of porous hierarchical polymer/ceramic composites by electron irradiation of organic/inorganic polymers: route to a highly durable, large-area superhydrophobic coating.

PubMed

Lee, Eun Je; Kim, Jae Joon; Cho, Sung Oh

2010-03-02

Polymer/ceramic composite films with micro- and nanocombined hierarchical structures are fabricated by electron irradiation of poly(methyl methacrylate) (PMMA) microspheres/silicone grease. Electron irradiation induces volume contraction of PMMA microspheres and simultaneously transforms silicone grease into a ceramic material of silicon oxycarbide with many nanobumps. As a result, highly porous structures that consist of micrometer-sized pores and microparticles decorated with nanobumps are created. The fabricated films with the porous hierarchical structure exhibit good superhydrophobicity with excellent self-cleaning and antiadhesion properties after surface treatment with fluorosilane. In addition, the porous hierarchical structures are covered with silicon oxycarbide, and thus the superhydrophobic coatings have high hardness and strong adhesion to the substrate. The presented technique provides a straightforward route to producing large-area, mechanically robust superhydrophobic films on various substrate materials.

An Accelerated Release Method of Risperidone Loaded PLGA Microspheres with Good IVIVC.

PubMed

Hu, Xiaoqin; Zhang, Jianwei; Tang, Xuemei; Li, Mingyuan; Ma, Siyu; Liu, Cheng; Gao, Yue; Zhang, Yue; Liu, Yan; Yu, Fanglin; Yang, Yang; Guo, Jia; Li, Zhiping; Mei, Xingguo

2018-01-01

A long release period lasting several days or several weeks is always needed and thereby it is tedious and time consuming to screen formulations of such microspheres with so long release period and evaluate their release profiles in vitro with conventional long-term or "real-time" release method. So, an accelerated release testing of such system is necessary for formulation design as well as quality control purpose. The purpose of this study is to obtain an accelerated release method of risperidone loaded poly(lactic-co-glycolic acid) (PLGA) microspheres with good in vitro/in vivo correlation (IVIVC). Two formulations of risperidone loaded PLGA microspheres used for evaluating IVIVC were prepared by O/W method. The accelerated release condition was optimized by investigating the effect of pH, osmotic pressure, temperature and ethanol concentration on the release of risperidone from microspheres and the in vitro accelerated release profiles of risperidone from PLGA microspheres were obtained under this optimized accelerated release condition. The plasma concentration of risperidone were also detected after subcutaneous injection of risperidone loaded microspheres to rats. The in vivo cumulative absorption profiles were then calculated using Wagner-Nelson model, Loo- Riegelman model and numerical convolution model, respectively. The correlation between in vitro accelerated release and in vivo cumulative absorption were finally evaluated with Least Square Method. It was shown that temperature and ethanol concentration significantly affected the release of risperidone from the microspheres while pH and osmotic pressure of release media slightly affected the release behavior of risperidone. The in vitro release of risperidone from microspheres were finally undergone in PBS (pH7.0, 300mosm) with 20% (V/V) ethanol at 45°C. The sustained and complete release of risperidone was observed in both formulations under the accelerated release condition although these two release

PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination.

PubMed

Garinot, Marie; Fiévez, Virginie; Pourcelle, Vincent; Stoffelbach, François; des Rieux, Anne; Plapied, Laurence; Theate, Ivan; Freichels, Hélène; Jérôme, Christine; Marchand-Brynaert, Jacqueline; Schneider, Yves-Jacques; Préat, Véronique

2007-07-31

To improve the efficiency of orally delivered vaccines, PEGylated PLGA-based nanoparticles displaying RGD molecules at their surface were designed to target human M cells. RGD grafting was performed by an original method called "photografting" which covalently linked RGD peptides mainly on the PEG moiety of the PCL-PEG, included in the formulation. First, three non-targeted formulations with size and zeta potential adapted to M cell uptake and stable in gastro-intestinal fluids, were developed. Their transport by an in vitro model of the human Follicle associated epithelium (co-cultures) was largely increased as compared to mono-cultures (Caco-2 cells). RGD-labelling of nanoparticles significantly increased their transport by co-cultures, due to interactions between the RGD ligand and the beta(1) intregrins detected at the apical surface of co-cultures. In vivo studies demonstrated that RGD-labelled nanoparticles particularly concentrated in M cells. Finally, ovalbumin-loaded nanoparticles were orally administrated to mice and induced an IgG response, attesting antigen ability to elicit an immune response after oral delivery.

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.

Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing.

PubMed

Schrier, J A; Fink, B F; Rodgers, J B; Vasconez, H C; DeLuca, P P

2001-10-07

The hypothesis of this research was that implants of poly(lactide-co-glycolide) (PLGA) microspheres loaded with bone morphogenetic protein-2 (rhBMP-2) and distributed in a freeze-dried carboxymethylcellulose (CMC) matrix would produce more new bone than would matrix implants of non-protein-loaded microspheres or matrix implants of only CMC. To test this hypothesis it was necessary to fashion microsphere-loaded CMC implants that were simple to insert, fit precisely into a defect, and would not elicit swelling. Microspheres were produced via a water-in-oil-in-water double-emulsion system and were loaded with rhBMP-2 by soaking them in a buffered solution of the protein at a concentration of 5.4 mg protein per gram of PLGA. Following recovery of the loaded microspheres by lyophilization, matrices for implantation were prepared by lyophilizing a suspension of the microspheres in 2% CMC in flat-bottom tissue culture plates. Similar matrices were made with 2% CMC and with 2% CMC containing blank microspheres. A full-thickness calvarial defect model in New Zealand white rabbits was used to assess bone growth. Implants fit the defect well, allowing for direct application. Six weeks postsurgery, defects were collected and processed for undecalcified histology. In vitro, 60% of the loaded rhBMP-2 released from devices or microspheres in 5 to 7 days, with the unembedded microspheres releasing faster than those embedded in CMC. In vivo, the rhBMP-2 microspheres greatly enhanced bone healing, whereas nonloaded PLGA microspheres in the CMC implants had little effect. The results showed that a lyophilized device of rhBMP-2/PLGA microspheres in CMC was an effective implantable protein-delivery system for use in bone repair.

A comparison study on the behavior of human endometrial stem cell-derived osteoblast cells on PLGA/HA nanocomposite scaffolds fabricated by electrospinning and freeze-drying methods.

PubMed

Namini, Mojdeh Salehi; Bayat, Neda; Tajerian, Roxana; Ebrahimi-Barough, Somayeh; Azami, Mahmoud; Irani, Shiva; Jangjoo, Saranaz; Shirian, Sadegh; Ai, Jafar

2018-03-27

An engineered tissue structure is an artificial scaffold combined with cells and signaling factors. Among various polymers, the polylactide-co-glycolide/hydroxyapatite (PLGA/HA) has attracted much attention due to their optimal properties. The aim of this study was to study the behavior of human endometrial stem cell (hEnSC)-derived osteoblast cells cultured on PLGA/HA nanocomposite scaffolds. hEnSCs were isolated and exposed to osteogenic media for 21 days. Differentiated cells were cultured on PLGA/HA synthetic scaffolds. The PLGA/HA-based nanocomposite scaffolds were fabricated using either electrospinning or freeze-drying methods. Behavior of the cells was evaluated a week after seeding hEnSC-derived osteoblast-like cells on these scaffolds. Osteogenesis was investigated in terms of alkaline phosphatase activity, gene expression, immunocytochemistry (ICC), proliferation, and scanning electron microscopy (SEM). Moreover, scaffold properties, such as pore size and morphology of the cells, onto the scaffolds were evaluated using SEM. Furthermore, biocompatibility of these scaffolds was confirmed by 3-(4,5-dimethylthiazoyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The matrix mineralization was proved by alizarin red staining, and the osteogenic media-treated cultures positively expressed osteocalcin and osteopontin markers. Moreover, qRT-PCR results confirmed the positive gene expression of osteopontin and osteonectin in the differentiated osteoblast-like cells. The results of behavior assessment of the cultured cells on electrospinning and freeze-dried scaffolds showed that the behavior of the cultured cells on the freeze-dried PLGA/HA scaffolds was significantly better than the electrospinning PLGA/HA scaffolds. It has been shown that the freeze-dried PLGA/HA nanocomposite scaffolds can appropriately support the attachment and proliferation of the differentiated osteoblast cells and are a suitable candidate for bone tissue engineering.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reduction of inflammatory responses and enhancement of extracellular matrix formation by vanillin-incorporated poly(lactic-co-glycolic acid) scaffolds.

PubMed

Lee, Yujung; Kwon, Jeongil; Khang, Gilson; Lee, Dongwon

2012-10-01

Vanillin is one of the major components of vanilla, a commonly used flavoring agent and preservative and is known to exert potent antioxidant and anti-inflammatory activities. In this work, vanillin-incorporated poly(lactic-co-glycolic acid) (PLGA) films and scaffolds were fabricated to evaluate the effects of vanillin on the inflammatory responses and extracellular matrix (ECM) formation in vitro and in vivo. The incorporation of vanillin to PLGA films induced hydrophilic nature, resulting in the higher cell attachment and proliferation than the pure PLGA film. Vanillin also reduced the generation of reactive oxygen species (ROS) in cells cultured on the pure PLGA film and significantly inhibited the PLGA-induced inflammatory responses in vivo, evidenced by the reduced accumulation of inflammatory cells and thinner fibrous capsules. The effects of vanillin on the ECM formation were evaluated using annulus fibrous (AF) cell-seeded porous PLGA/vanillin scaffolds. PLGA/vanillin scaffolds elicited the more production of glycosaminoglycan and collagen than the pure PLGA scaffold, in a concentration-dependent manner. Based on the low level of inflammatory responses and enhanced ECM formation, vanillin-incorporated PLGA constructs make them promising candidates in the future biomedical applications.

Convenient and large-scale synthesis of nitrogen-rich hierarchical porous carbon spheres for supercapacitors and CO2 capture

NASA Astrophysics Data System (ADS)

Chang, Binbin; Zhang, Shouren; Yin, Hang; Yang, Baocheng

2017-08-01

Herein, considering the great potential of nitrogen-doped hierarchical porous carbons in energy storage and CO2 capture, we designed a convenient and easily large-scale production strategy for preparing nitrogen-doped hierarchical porous carbon sphere (NHPCS) materials. In this synthesis route, spherical resorcinol-formaldehyde (RF) resins were selected as carbon precursor, and then the ZnCl2-impregnated RF resin spheres were carbonized in a NH3 atmosphere at a temperature range of 600-800 °C. During the one-step heat-treatment process, nitrogen atom could be efficiently incorporated into the carbon skeleton, and the interconnected and hierarchical pore structure with different micro/mesopore proportion could be generated and tuned by adjusting the activating agent ZnCl2 dosage and carbonization temperature. The resultant nitrogen-doped hierarchical porous carbon sphere materials exhibited a satisfactory charge storage capacity, and the optimal sample of NHPCS-2-8 with a high mesopore proportion obtained at 800 °C with a ZnCl2/RF mass ratio of 2:1 presented a specific capacitance of 273.8 F g-1 at a current density of 0.5 A g-1. More importantly, the assembled NHPCS-2-8-based symmetric capacitor displayed a high energy density of 17.2 Wh kg-1 at a power density of 178.9 W kg-1 within a voltage window of 0 ∼ 1.8 V in 0.5 M Na2SO4 aqueous electrolyte. In addition, the CO2 capture application of these NHPCS materials was also explored, and the optimal sample of NHPCS-0-8 with a large micropore proportion prepared at 800 °C exhibited an exceptional CO2 uptake capacity at ambient pressures of up to 4.23 mmol g-1 at 0 °C.

Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

PubMed Central

Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

2015-01-01

Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid) and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116). The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy. PMID:25692854

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

PubMed Central

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

2016-01-01

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. PMID:26706541

Sustained Release of Lidocaine from Solvent-Free Biodegradable Poly[(d,l)-Lactide-co-Glycolide] (PLGA): In Vitro and In Vivo Study.

PubMed

Kau, Yi-Chuan; Liao, Chia-Chih; Chen, Ying-Chi; Liu, Shih-Jung

2014-09-16

Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l)-lactide-co-glycolide] (PLGA) was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm) and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release) and reached completion around day 28. Scanning electron microscope (SEM) photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered). In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.

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

PubMed

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

2011-06-17

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.

The binary complex of poly(PEGMA-co-MAA) hydrogel and PLGA nanoparticles as a novel oral drug delivery system for ibuprofen delivery.

PubMed

Shang, Qing; Huang, Sijin; Zhang, Aixin; Feng, Jia; Yang, Song

2017-11-01

To improve the bioavailability of ibuprofen (IBU), we developed a novel binary complex of poly(PEGMA-co-MAA) hydrogel and IBU-loaded PLGA nanoparticles (IBU-PLGA NPs@hydrogels) as an oral intestinal targeting drug delivery system (OIDDS). The IBU-loaded PLGA NPs and pH-sensitive hydrogels were obtained via the solvent evaporation method and radical polymerization, respectively. The final OIDDS was obtained by immersing the hydrogel chips in the IBU-loaded PLGA NPs solutions (pH 7.4) for 3 d. The size distribution and morphology of cargo-free NPs were studied by laser granularity analyzer and transmission electron microscope (TEM). The inner structures of the pH-sensitive hydrogel chips were observed with an S-4800 scanning electron microscope (SEM). The distribution states of IBU in the OIDDS were also studied with X-ray diffraction (XRD) and differential scanning calorimetry (DSC). TEM photographs illustrated that the PLGA NPs had a round shape with an average diameter about 100 nm. Fourier transform infrared spectrum (FTIR) confirmed the synthesis of poly(PEGMA-co-MAA) hydrogel. The SEM picture showed that the final hydrogel had 3D net-work structures. Moreover, the poly(PEGMA-co-MAA) hydrogel showed an excellent pH-sensitivity. The XRD and DSC curves suggested that IBU distributed in the OIDDS with an amorphous state. The cumulated release profiles indicated that the final OIDDS could release IBU in alkaline environment (e.g. intestinal tract) at a sustained manner. Therefore, the novel OIDDS could improve the oral bioavailability of IBU, and had a potential application in drug delivery.

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

PubMed

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

2012-01-01

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

Transferrin-conjugated lipid-coated PLGA nanoparticles for targeted delivery of aromatase inhibitor 7alpha-APTADD to breast cancer cells.

PubMed

Zheng, Yu; Yu, Bo; Weecharangsan, Wanlop; Piao, Longzhu; Darby, Michael; Mao, Yicheng; Koynova, Rumiana; Yang, Xiaojuan; Li, Hong; Xu, Songlin; Lee, L James; Sugimoto, Yasuro; Brueggemeier, Robert W; Lee, Robert J

2010-05-10

Transferrin (Tf)-conjugated lipid-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles carrying the aromatase inhibitor, 7alpha-(4'-amino)phenylthio-1,4-androstadiene-3,17-dione (7alpha-APTADD), were synthesized by a solvent injection method. Formulation parameters including PLGA-to-lipid, egg PC-to-TPGS, and drug-to-PLGA ratios and aqueous-to-organic phase ratio at the point of synthesis were optimized to obtain nanoparticles with desired sizes and drug loading efficiency. The optimal formulation had a drug loading efficiency of 36.3+/-3.4%, mean diameter of 170.3+/-7.6nm and zeta potential of -18.9+/-1.5mV. The aromatase inhibition activity of the nanoparticles was evaluated in SKBR-3 breast cancer cells. IC(50) value of the Tf-nanoparticles was ranging from 0.77 to 1.21nM, and IC(50) value of the nanoparticles was ranging from 1.90 to 3.41nM (n=3). The former is significantly lower than the latter (p<0.05). These results suggested that the aromatase inhibition activity of the Tf-nanoparticles was enhanced relative to that of the non-targeted nanoparticles, which was attributable to Tf receptor (TfR) mediated uptake. In conclusion, Tf-conjugated lipid-coated PLGA nanoparticles are potential vehicles for improving the efficiency and specificity of therapeutic delivery of aromatase inhibitors. Copyright 2010 Elsevier B.V. All rights reserved.

Preparation and investigation of P28GST-loaded PLGA microparticles for immunomodulation of experimental colitis.

PubMed

Thi, T H Hoang; Priemel, P A; Karrout, Y; Driss, V; Delbeke, M; Dendooven, A; Flament, M P; Capron, M; Siepmann, J

2017-11-25

The aim of this work was to prepare and characterize (in vitro and in vivo) PLGA-based microparticles loaded with an enzymatic protein derived from the helminth parasite Schistosoma haematobium: glutathione S-transferase P28GST (P28GST). This protein is not only a promising candidate vaccine against schistosomiasis, it also exhibits interesting immunomodulating effects, which can be helpful for the regulation of inflammatory diseases. Helminths express a regulatory role on intestinal inflammation, and immunization by P28GST has recently been shown to be as efficient as infection to reduce inflammation in a murine colitis model. As an alternative to the combination with a classical adjuvant, long acting P28GST microparticles were prepared in order to induce colitis prevention. PLGA was used as biodegradable and biocompatible matrix former, and a W/O/W emulsion/solvent extraction technique applied to prepare different types of microparticles. The effects of key formulation and processing parameters (e.g., the polymer molecular weight, drug loading, W/O/W phase volumes and stirring rates of the primary/secondary emulsions) on the systems' performance were studied. Microparticles providing about constant P28GST release during several weeks were selected and their effects in an experimental model of colitis evaluated. Mice received P28GST-loaded or P28GST-free PLGA microparticles (s.c.) on Day 0, and optionally also on Days 14 and 28. Colitis was induced on Day 35, the animals were sacrificed on Day 37. Interestingly, the Wallace score (being a measure of the severity of the inflammation) was significantly lower in mice treated with P28GST microparticles compared to placebo after 1 or 3 injections. As immunogenicity markers, increased anti-P28GST IgG levels were detected after three P28GST PLGA microparticle injections, but not in the control groups. Thus, the proposed microparticles offer an interesting potential for the preventive treatment of experimental colitis

A Large-Surface-Area Boracite-Network-Topology Porous MOF Constructed from a Conjugated Ligand Exhibiting a High Hydrogen Uptake Capacity

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

Wang, Xi-Sen; Ma, Shengqian; Yuan, Daqiang

2009-01-01

A new porous metal-organic framework, PCN-20 with a twisted boracite net topology, was constructed based on a highly conjugated planar tricarboxylate ligand; PCN-20 possesses a large Langmuir surface area of over 4200 m(2)/g as well as demonstrates a high hydrogen uptake capacity of 6.2 wt % at 77 K and 50 bar.

Sputtering from a Porous Material by Penetrating Ions

NASA Technical Reports Server (NTRS)

Rodriguez-Nieva, J. F.; Bringa, E. M.; Cassidy, T. A.; Johnson, R. E.; Caro, A.; Fama, M.; Loeffler, M.; Baragiola, R. A.; Farkas, D.

2012-01-01

Porous materials are ubiquitous in the universe and weathering of porous surfaces plays an important role in the evolution of planetary and interstellar materials. Sputtering of porous solids in particular can influence atmosphere formation, surface reflectivity, and the production of the ambient gas around materials in space, Several previous studies and models have shown a large reduction in the sputtering of a porous solid compared to the sputtering of the non-porous solid. Using molecular dynamics simulations we study the sputtering of a nanoporous solid with 55% of the solid density. We calculate the electronic sputtering induced by a fast, penetrating ion, using a thermal spike representation of the deposited energy. We find that sputtering for this porous solid is, surprisingly, the same as that for a full-density solid, even though the sticking coefficient is high.

Layering PLGA-based electrospun membranes and cell sheets for engineering cartilage-bone transition.

PubMed

Mouthuy, P-A; El-Sherbini, Y; Cui, Z; Ye, H

2016-04-01

It is now widely acknowledged that implants that have been designed with an effort towards reconstructing the transition between tissues might improve their functionality and integration in vivo. This paper contributes to the development of improved treatment for articular cartilage repair by exploring the potential of the combination of electrospinning technology and cell sheet engineering to create cartilage tissue. Poly(lactic-co-glycolic acid) (PLGA) was used to create the electrospun membranes. The focus being on the cartilage-bone transition, collagen type I and hydroxyapatite (HA) were also added to the scaffolds to increase the histological biocompatibility. Human mesenchymal stem cells (hMSCs) were cultured in thermoresponsive dishes to allow non-enzymatic removal of an intact cell layer after reaching confluence. The tissue constructs were created by layering electrospun membranes with sheets of hMSCs and were cultured under chondrogenic conditions for up to 21 days. High viability was found to be maintained in the multilayered construct. Under chondrogenic conditions, reverse-transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry have shown high expression levels of collagen type X, a form of collagen typically found in the calcified zone of articular cartilage, suggesting an induction of chondrocyte hypertrophy in the PLGA-based scaffolds. To conclude, this paper suggests that layering electrospun scaffolds and cell sheets is an efficient approach for the engineering of tissue transitions, and in particular the cartilage-bone transition. The use of PLGA-based scaffold might be particularly useful for the bone-cartilage reconstruction, since the differentiated tissue constructs seem to show characteristics of calcified cartilage. Copyright © 2013 John Wiley & Sons, Ltd.

Reverse freeze casting: a new method for fabricating highly porous titanium scaffolds with aligned large pores.

PubMed

Yook, Se-Won; Jung, Hyun-Do; Park, Chang-Hoon; Shin, Kwan-Ha; Koh, Young-Hag; Estrin, Yuri; Kim, Hyoun-Ee

2012-07-01

Highly porous titanium with aligned large pores up to 500 μm in size, which is suitable for scaffold applications, was successfully fabricated using the reverse freeze casting method. In this process we have newly developed, the Ti powders migrated spontaneously along the pre-aligned camphene boundaries at a temperature of 45.5°C and formed a titanium-camphene mixture with an aligned structure; this was followed by freeze drying and sintering. As the casting time increased from 24 to 48 h, the initial columnar structures turned into lamellar structures, with the porosity decreasing from 69 to 51%. This reduction in porosity caused the compressive yield strength to increase from 121 to 302 MPa, with an elastic modulus of the samples being in the range of 2-5 GPa. In addition, it was demonstrated that reverse freeze casting can also be successfully applied to various other raw powders, suggesting that the method developed in this work opens up new avenues for the production of a range of porous metallic and ceramic scaffolds with highly aligned pores. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Highly porous carbon with large electrochemical ion absorption capability for high-performance supercapacitors and ion capacitors.

PubMed

Wang, Shijie; Wang, Rutao; Zhang, Yabin; Zhang, Li

2017-11-03

Carbon-based supercapacitors have attracted extensive attention as the complement to batteries, owing to their durable lifespan and superiority in high-power-demand fields. However, their widespread use is limited by the low energy storage density; thus, a high-surface-area porous carbon is urgently needed. Herein, a highly porous carbon with a Brunauer-Emmett-Teller specific surface area up to 3643 m 2 g -1 has been synthesized by chemical activation of papayas for the first time. This sp 2 -bonded porous carbon has a continuous three-dimensional network of highly curved, atom-thick walls that form narrow mesopores of 2 ∼ 5 nm in width, which can be systematically tailored with varied activation levels. Two-electrode symmetric supercapacitors constructed by this porous carbon achieve energy density of 8.1 Wh kg -1 in aqueous electrolyte and 65.5 Wh kg -1 in ionic-liquid electrolyte. Furthermore, half-cells (versus Li or Na metal) using this porous carbon as ion sorption cathodes yield high specific capacity, e.g., 51.0 and 39.3 mAh g -1 in Li + and Na + based organic electrolyte. These results underline the possibility of obtaining the porous carbon for high-performance carbon-based supercapacitors and ion capacitors in a readily scalable and economical way.

Highly porous carbon with large electrochemical ion absorption capability for high-performance supercapacitors and ion capacitors

NASA Astrophysics Data System (ADS)

Wang, Shijie; Wang, Rutao; Zhang, Yabin; Zhang, Li

2017-11-01

Carbon-based supercapacitors have attracted extensive attention as the complement to batteries, owing to their durable lifespan and superiority in high-power-demand fields. However, their widespread use is limited by the low energy storage density; thus, a high-surface-area porous carbon is urgently needed. Herein, a highly porous carbon with a Brunauer-Emmett-Teller specific surface area up to 3643 m2 g-1 has been synthesized by chemical activation of papayas for the first time. This sp2-bonded porous carbon has a continuous three-dimensional network of highly curved, atom-thick walls that form narrow mesopores of 2 ˜ 5 nm in width, which can be systematically tailored with varied activation levels. Two-electrode symmetric supercapacitors constructed by this porous carbon achieve energy density of 8.1 Wh kg-1 in aqueous electrolyte and 65.5 Wh kg-1 in ionic-liquid electrolyte. Furthermore, half-cells (versus Li or Na metal) using this porous carbon as ion sorption cathodes yield high specific capacity, e.g., 51.0 and 39.3 mAh g-1 in Li+ and Na+ based organic electrolyte. These results underline the possibility of obtaining the porous carbon for high-performance carbon-based supercapacitors and ion capacitors in a readily scalable and economical way.

Comparative Kinetic Analysis of Closed-Ended and Open-Ended Porous Sensors

NASA Astrophysics Data System (ADS)

Zhao, Yiliang; Gaur, Girija; Mernaugh, Raymond L.; Laibinis, Paul E.; Weiss, Sharon M.

2016-09-01

Efficient mass transport through porous networks is essential for achieving rapid response times in sensing applications utilizing porous materials. In this work, we show that open-ended porous membranes can overcome diffusion challenges experienced by closed-ended porous materials in a microfluidic environment. A theoretical model including both transport and reaction kinetics is employed to study the influence of flow velocity, bulk analyte concentration, analyte diffusivity, and adsorption rate on the performance of open-ended and closed-ended porous sensors integrated with flow cells. The analysis shows that open-ended pores enable analyte flow through the pores and greatly reduce the response time and analyte consumption for detecting large molecules with slow diffusivities compared with closed-ended pores for which analytes largely flow over the pores. Experimental confirmation of the results was carried out with open- and closed-ended porous silicon (PSi) microcavities fabricated in flow-through and flow-over sensor configurations, respectively. The adsorption behavior of small analytes onto the inner surfaces of closed-ended and open-ended PSi membrane microcavities was similar. However, for large analytes, PSi membranes in a flow-through scheme showed significant improvement in response times due to more efficient convective transport of analytes. The experimental results and theoretical analysis provide quantitative estimates of the benefits offered by open-ended porous membranes for different analyte systems.

Poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped trans-cinnamaldehyde and eugenol for antimicrobial delivery applications.

PubMed

Gomes, Carmen; Moreira, Rosana G; Castell-Perez, Elena

2011-03-01

Eugenol and trans-cinnamaldehyde are natural compounds known to be highly effective antimicrobials; however, both are hydrophobic molecules, a limitation to their use within the food industry. The goal of this study was to synthesize spherical poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped eugenol and trans-cinnamaldehyde for future antimicrobial delivery applications. The emulsion evaporation method was used to form the nanoparticles in the presence of poly (vinyl alcohol) (PVA) as a surfactant. The inclusion of antimicrobial compounds into the PLGA nanoparticles was accomplished in the organic phase. Synthesis was followed by ultrafiltration (performed to eliminate the excess of PVA and antimicrobial compound) and freeze-drying. The nanoparticles were characterized by their shape, size, entrapment efficiency, and antimicrobial efficiency. The entrapment efficiency for eugenol and trans-cinnamaldehyde was approximately 98% and 92%, respectively. Controlled release experiments conducted in vitro at 37 °C and 100 rpm for 72 h showed an initial burst followed by a slower rate of release of the antimicrobial entrapped inside the PLGA matrix. All loaded nanoparticles formulations proved to be efficient in inhibiting growth of Salmonella spp. (Gram-negative bacterium) and Listeria spp. (Gram-positive bacterium) with concentrations ranging from 20 to 10 mg/mL. Results suggest that the application of these antimicrobial nanoparticles in food systems may be effective at inhibiting specific pathogens. Nanoencapsulation of lipophilic antimicrobial compounds has great potential for improving the effectiveness and efficiency of delivery in food systems. This study consisted of synthesizing PLGA nanoparticles with entrapped eugenol and trans-cinnamaldehyde. By characterizing these new delivery systems, one can understand the controlled-release mechanism and antimicrobial efficiency that provides a foundation that will enable food manufacturers to design

Clinical use of the resorbable bioscaffold poly lactic co-glycolic acid (PLGA) in post-extraction socket for maintaining the alveolar height: A prospective study.

PubMed

Hoda, Nadeemul; Saifi, Aamir Malick; Giraddi, Girish B

2016-01-01

A common sequel of tooth extraction is alveolar bone resorption. It makes the placement of dental implants difficult and creates an esthetic problem for the fabrication of conventional prostheses. Therefore, alveolar bone following tooth extraction should be preserved. The present prospective study was conducted to evaluate the efficacy of the resorbable bioscaffold poly lactic co-glycolic acid (PLGA) in maintaining the alveolar height in post-extraction socket. 20 patients were selected based on inclusion and exclusion criteria and were randomly divided into two groups: cases and control comprising of 10 patients each. Atraumatic tooth extraction was done in all patients. PLGA bioscaffold was placed in cases and socket was closed with 3-0 vicryl. In control group, socket was directly closed with 3-0 vicryl. The patients were kept on follow-up and complications such as dry socket, pain, and swelling were recorded. IOPA were taken at 1st, 4th, 12th, and 24th week to record changes in the height of alveolar bone. The radiographic measurements were compared and the differences were statistically analyzed. Reduction in alveolar bone height after placement of PLGA bioscaffold was significantly less in cases as compared to controls at 4th, 12th, and 24th week following extraction. No complications were observed throughout the follow-up period. PLGA scaffold significantly reduces bone resorption. Application is very simple and can be easily performed in a dental setup. However, PLGA scaffold adds significantly to the cost of treatment.

Multivariate analysis for the optimization of microfluidics-assisted nanoprecipitation method intended for the loading of small hydrophilic drugs into PLGA nanoparticles.

PubMed

Chiesa, E; Dorati, R; Modena, T; Conti, B; Genta, I

2018-01-30

Design of Experiment-assisted evaluation of critical process (total flow rate, TFR, flow rate ratio, FRR) and formulation (polymer concentration and structure, drug:polymer ratio) variables in a novel microfluidics-based device, a staggered herringbone micromixer (SHM), for poly(lactic-co-glycolic acid) copolymer (PLGA) nanoparticles (NPs) manufacturing was performed in order to systematically evaluate and mathematically describe their effects on NPs sizes and drug encapsulation; a small hydrophilic moiety, N-acetylcysteine, was chosen as challenging model drug. SHM-assisted nanoprecipitation method consistently yielded NPs with tailor made sizes (in the range of 100-900 nm) and polydispersity index range from 0.061 to 0.286. Significant effects on NPs sizes were highlighted for TFR and FRR: increasing TFR (from 5 to 15 mL/min) and decreasing FRR (from 1:1 to 1:5 v/v, acetonitrile: buffer) NPs with mean diameter <200 nm were obtained. SHM technique allowed for flexible, application-specific tuning of PLGA NPs size using organic solvents with relatively low toxicity (acetone, acetonitrile), varying aqueous phase composition (Tris buffer vs PVA aqueous solution) and PLGA characteristics (Mw ranging from 25-90 kDa, capped or un-capped PLGA, different lactide:glycolide molar ratio). A very satisfactory N-Ac encapsulation efficiency (more than 67%) and a prolonged release (by 168 h) were achieved. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Fabrication aspects of PLA-CaP/PLGA-CaP composites for orthopedic applications: a review.

PubMed

Zhou, Huan; Lawrence, Joseph G; Bhaduri, Sarit B

2012-07-01

For several decades, composites made of polylactic acid-calcium phosphates (PLA-CaP) and polylactic acid-co-glycolic acid-calcium phosphates (PLGA-CaP) have seen widespread uses in orthopedic applications. This paper reviews the fabrication aspects of these composites, following the ubiquitous materials science approach by studying "processing-structure-property" correlations. Various fabrication processes such as microencapsulation, phase separation, electrospinning, supercritical gas foaming, etc., are reviewed, with specific examples of their applications in fabricating these composites. The effect of the incorporation of CaP materials on the mechanical and biological performance of PLA/PLGA is addressed. In addition, this paper describes the state of the art on challenges and innovations concerning CaP dispersion, incorporation of biomolecules/stem cells and long-term degradation of the composites. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

PubMed

García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

2015-03-30

Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

The regulation of focal adhesion complex formation and salivary gland epithelial cell organization by nanofibrous PLGA scaffolds

PubMed Central

Sequeira, Sharon J.; Soscia, David A.; Oztan, Basak; Mosier, Aaron P.; Jean-Gilles, Riffard; Gadre, Anand; Cady, Nathaniel C.; Yener, Bülent; Castracane, James; Larsen, Melinda

2012-01-01

Nanofiber scaffolds have been useful for engineering tissues derived from mesenchymal cells, but few studies have investigated their applicability for epithelial cell-derived tissues. In this study, we generated nanofiber (250 nm) or microfiber (1200 nm) scaffolds via electrospinning from the polymer, poly-L-lactic-co-glycolic acid (PLGA). Cell-scaffold contacts were visualized using fluorescent immunocytochemistry and laser scanning confocal microscopy. Focal adhesion (FA) proteins, such as phosphorylated FAK (Tyr397), paxillin (Tyr118), talin and vinculin were localized to FA complexes in adult cells grown on planar surfaces but were reduced and diffusely localized in cells grown on nanofiber surfaces, similar to the pattern observed in adult mouse salivary gland tissues. Significant differences in epithelial cell morphology and cell clustering were also observed and quantified, using image segmentation and computational cell-graph analyses. No statistically significant differences in scaffold stiffness between planar PLGA film controls compared to nanofibers scaffolds were detected using nanoindentation with atomic force microscopy, indicating that scaffold topography rather than mechanical properties accounts for changes in cell attachments and cell structure. Finally, PLGA nanofiber scaffolds could support the spontaneous self-organization and branching of dissociated embryonic salivary gland cells. Nanofiber scaffolds may therefore have applicability in the future for engineering an artificial salivary gland. PMID:22285464

Porous Networks Through Colloidal Templates

NASA Astrophysics Data System (ADS)

Li, Qin; Retsch, Markus; Wang, Jianjun; Knoll, Wolfgang; Jonas, Ulrich

Porous networks represent a class of materials with interconnected voids with specific properties concerning adsorption, mass and heat transport, and spatial confinement, which lead to a wide range of applications ranging from oil recovery and water purification to tissue engineering. Porous networks with well-defined, highly ordered structure and periodicities around the wavelength of light can furthermore show very sophisticated optical properties. Such networks can be fabricated from a very large range of materials by infiltration of a sacrificial colloidal crystal template and subsequent removal of the template. The preparation procedures reported in the literature are discussed in this review and the resulting porous networks are presented with respect to the underlying material class. Furthermore, methods for hierarchical superstructure formation and functionalization of the network walls are discussed.

Preparation and in vitro/in vivo evaluation of PLGA microspheres containing norquetiapine for long-acting injection.

PubMed

Park, Chun-Woong; Lee, Hyo-Jung; Oh, Dong-Won; Kang, Ji-Hyun; Han, Chang-Soo; Kim, Dong-Wook

2018-01-01

Norquetiapine ( N -desalkyl quetiapine, NQ) is an active metabolite of quetiapine with stable pharmacokinetic and pharmacological properties. However, its short half-life is a drawback for clinical applications, and long-acting formulations are required. The objectives of this study were to prepare improved entrapment efficiency NQ freebase microspheres by the solvent evaporation method with poly(d,l-lactic-co-glycolic acid) (PLGA) as a release modulator and to evaluate their physicochemical and in vitro/in vivo release properties. NQ freebase PLGA (1:5 w/w) formulations were prepared by the oil-in-water (o/w) emulsion-solvent evaporation method. A solution of the drug and PLGA in 9:1 v/v dichloromethane:ethanol was mixed with 0.2% polyvinyl alcohol and homogenized at 2,800 rpm. The emulsion was stirred for 3 h to dilute and evaporate the solvent. After that, the resulting product was freeze-dried. Drug-loading capacity was measured by the validated RP-HPLC method. The surface morphology of the microspheres was observed by scanning electron microscopy (SEM), and the physicochemical properties were evaluated by differential scanning calorimetry, powder X-ray diffraction, and Fourier-transform infrared spectroscopy particle size distribution. The in vitro dissolution test was performed using a rotary shaking bath at 37°C, with constant shaking at 50 rpm in sink condition. The NQ freebase microspheres prepared by o/w emulsion-solvent evaporation showed over 30% efficiency. NQ was confirmed to be amorphous in the microspheres by powder X-ray diffraction and differential scanning calorimetry. Special chemical interaction in the microspheres was not observed by FT-IR. The in vitro dissolution test demonstrated that the prepared microspheres' release properties were maintained for more than 20 days. The in vivo test also confirmed that the particles' long acting properties were maintained. Therefore, good in vitro-in vivo correlation was established. In this study, NQ

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.

Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA.

PubMed

Jensen, Ditte Krohn; Jensen, Linda Boye; Koocheki, Saeid; Bengtson, Lasse; Cun, Dongmei; Nielsen, Hanne Mørck; Foged, Camilla

2012-01-10

Matrix systems based on biocompatible and biodegradable polymers like the United States Food and Drug Administration (FDA)-approved polymer poly(DL-lactide-co-glycolide acid) (PLGA) are promising for the delivery of small interfering RNA (siRNA) due to favorable safety profiles, sustained release properties and improved colloidal stability, as compared to polyplexes. The purpose of this study was to design a dry powder formulation based on cationic lipid-modified PLGA nanoparticles intended for treatment of severe lung diseases by pulmonary delivery of siRNA. The cationic lipid dioleoyltrimethylammoniumpropane (DOTAP) was incorporated into the PLGA matrix to potentiate the gene silencing efficiency. The gene knock-down level in vitro was positively correlated to the weight ratio of DOTAP in the particles, and 73% silencing was achieved in the presence of 10% (v/v) serum at 25% (w/w) DOTAP. Optimal properties were found for nanoparticles modified with 15% (w/w) DOTAP, which reduced the gene expression with 54%. This formulation was spray-dried with mannitol into nanocomposite microparticles of an aerodynamic size appropriate for lung deposition. The spray-drying process did not affect the physicochemical properties of the readily re-dispersible nanoparticles, and most importantly, the in vitro gene silencing activity was preserved during spray-drying. The siRNA content in the powder was similar to the theoretical loading and the siRNA was intact, suggesting that the siRNA is preserved during the spray-drying process. Finally, X-ray powder diffraction analysis demonstrated that mannitol remained in a crystalline state upon spray-drying with PLGA nanoparticles suggesting that the sugar excipient might exert its stabilizing effect by sterical inhibition of the interactions between adjacent nanoparticles. This study demonstrates that spray-drying is an excellent technique for engineering dry powder formulations of siRNA nanoparticles, which might enable the local

Development of a new delivery system consisting in 'drug-in cyclodextrin-in PLGA nanoparticles'.

PubMed

Mura, Paola; Maestrelli, Francesca; Cecchi, Matteo; Bragagni, Marco; Almeida, Antonio

2010-01-01

A combined approach based on drug cyclodextrin (CD) complexation and loading into PLGA nanoparticles (NP) has been developed to improve oxaprozin therapeutic efficiency. This strategy exploits the solubilizing and stabilizing properties of CDs and the prolonged-release and targeting properties of PLGA NPs. Drug-loaded NPs, prepared by double-emulsion, were examined for dimensions, zeta-potential and entrapment efficiency. Solid-state studies demonstrated the absence of drug-polymer interactions and assessed the amorphous state of the drug-CD complex loaded into NPs. Drug release rate from NPs was strongly influenced by the presence and kind of CD used. The percentage released at 24 h varied from 16% (plain drug-loaded NPs) to 50% (drug-betaCD-loaded NPs) up to 100% (drug-methylbetaCD-loaded NPs). This result suggests the possibility of using CD complexation not only to promote, but also to regulate drug release rate from NPs, by selecting the proper type of CD or CD combination.

PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect.

PubMed

Acharya, Sarbari; Sahoo, Sanjeeb K

2011-03-18

As mortality due to cancer continues to rise, advances in nanotechnology have significantly become an effective approach for achieving efficient drug targeting to tumour tissues by circumventing all the shortcomings of conventional chemotherapy. During the past decade, the importance of polymeric drug-delivery systems in oncology has grown exponentially. In this context, poly(lactic-co-glycolic acid) (PLGA) is a widely used polymer for fabricating 'nanoparticles' because of biocompatibility, long-standing track record in biomedical applications and well-documented utility for sustained drug release, and hence has been the centre of focus for developing drug-loaded nanoparticles for cancer therapy. Such PLGA nanoparticles have also been used to develop proteins and peptides for nanomedicine, and nanovaccines, as well as a nanoparticle-based drug- and gene-delivery system for cancer therapy, and nanoantigens and growth factors. These drug-loaded nanoparticles extravasate through the tumour vasculature, delivering their payload into the cells by the enhanced permeability and retention (EPR) effect, thereby increasing their therapeutic effect. Ongoing research about drug-loaded nanoparticles and their delivery by the EPR effect to the tumour tissues has been elucidated in this review with clarity. Copyright © 2010 Elsevier B.V. All rights reserved.

PVA bio-nanocomposites: a new take-off using cellulose nanocrystals and PLGA nanoparticles.

PubMed

Rescignano, N; Fortunati, E; Montesano, S; Emiliani, C; Kenny, J M; Martino, S; Armentano, I

2014-01-01

The formation of a new generation of hybrid bio-nanocomposites is reported: these are intended at modulating the mechanical, thermal and biocompatibility properties of the poly(vinyl alcohol) (PVA) by the combination of cellulose nanocrystals (CNC) and poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) loaded with bovine serum albumin fluorescein isothiocynate conjugate (FITC-BSA). CNC were synthesized from microcrystalline cellulose by hydrolysis, while PLGA nanoparticles were produced by a double emulsion with subsequent solvent evaporation. Firstly, binary bio-nanocomposites with different CNC amounts were developed in order to select the right content of CNC. Next, ternary PVA/CNC/NPs bio-nanocomposites were developed. The addition of CNC increased the elongation properties without compromising the other mechanical responses. Thermal analysis underlined the nucleation effect of the synergic presence of cellulose and nanoparticles. Remarkably, bio-nanocomposite films are suitable to vehiculate biopolymeric nanoparticles to adult bone marrow mesenchymal stem cells successfully, thus representing a new tool for drug delivery strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

EGFR targeted PLGA nanoparticles using gemcitabine for treatment of pancreatic cancer.

PubMed

Aggarwal, Sahil; Yadav, Sachin; Gupta, Swati

2011-02-01

The present study aimed to prepare and characterize anti EGFR monoclonal antibody (mab) conjugated Gemcitabine loaded PLGA nanoparticles for their selective delivery to pancreatic cells and evaluation of the systems in vitro. It was observed that direct covalent coupling of antibodies to glutaraldehyde activated nanoparticles is an appropriate method to achieve cell-type specific drug carrier systems based on polymeric nanoparticles that have potential to be applied for targeted chemotherapy in EGFR positive cancer.

Porous carbon with a large surface area and an ultrahigh carbon purity via templating carbonization coupling with KOH activation as excellent supercapacitor electrode materials

NASA Astrophysics Data System (ADS)

Sun, Fei; Gao, Jihui; Liu, Xin; Pi, Xinxin; Yang, Yuqi; Wu, Shaohua

2016-11-01

Large surface area and good structural stability, for porous carbons, are two crucial requirements to enable the constructed supercapacitors with high capacitance and long cycling lifespan. Herein, we successfully prepare porous carbon with a large surface area (3175 m2 g-1) and an ultrahigh carbon purity (carbon atom ratio of 98.25%) via templating carbonization coupling with KOH activation. As-synthesized MTC-KOH exhibits excellent performances as supercapacitor electrode materials in terms of high specific capacitance and ultrahigh cycling stability. In a three electrode system, MTC-KOH delivers a high capacitance of 275 F g-1 at 0.5 A g-1 and still 120 F g-1 at a high rate of 30 A g-1. There is almost no capacitance decay even after 10,000 cycles, demonstrating outstanding cycling stability. In comparison, pre-activated MTC with a hierarchical pore structure shows a better rate capability than microporous MTC-KOH. Moreover, the constructed symmetric supercapacitor using MTC-KOH can achieve high energy densities of 8.68 Wh kg-1 and 4.03 Wh kg-1 with the corresponding power densities of 108 W kg-1 and 6.49 kW kg-1, respectively. Our work provides a simple design strategy to prepare highly porous carbons with high carbon purity for supercapacitors application.

Superparamagnetic PLGA-iron oxide microcapsules for dual-modality US/MR imaging and high intensity focused US breast cancer ablation.

PubMed

Sun, Yang; Zheng, Yuanyi; Ran, Haitao; Zhou, Yang; Shen, Hongxia; Chen, Yu; Chen, Hangrong; Krupka, Tianyi M; Li, Ao; Li, Pan; Wang, Zhibiao; Wang, Zhigang

2012-08-01

Organic/inorganic, hybrid, multifunctional, material-based platforms combine the merits of diverse functionalities of inorganic nanoparticles and the excellent biocompatibility of organic systems. In this work, superparamagnetic poly(lactic-co-glycolic acid) (PLGA) microcapsules (Fe(3)O(4)/PLGA) have been developed, as a proof-of-concept, for the application in ultrasound/magnetic resonance dual-modality biological imaging and enhancing the therapeutic efficiency of high intensity focused ultrasound (HIFU) breast cancer surgery in vitro and in vivo. Hydrophobic Fe(3)O(4) nanoparticles were successfully integrated into PLGA microcapsules by a typical double emulsion evaporation process. In this process, highly dispersed superparamagnetic Fe(3)O(4)/PLGA composite microcapsules with well-defined spherical morphology were obtained with an average diameter of 885.6 nm. The potential of these microcapsules as dual contrast agents for ultrasonography and magnetic resonance imaging were demonstrated in vitro and, also, preliminarily in vivo. Meanwhile, the prepared superparamagnetic composite microcapsules were administrated into rabbits bearing breast cancer model for the evaluation of the in vivo HIFU synergistic ablation efficiency caused by the introduction of such microcapsules. Our results showed that the employment of the composite microcapsules could efficiently enhance ultrasound imaging of cancer, and greatly enhance the HIFU ablation of breast cancer in rabbits. In addition, pathological examination was systematically performed to detect the structural changes of the target tissue caused by HIFU ablation. This finding demonstrated that successful introduction of these superparamagnetic microcapsules into HIFU cancer surgery provided an alternative strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy of cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Osteoblasts Interaction with PLGA Membranes Functionalized with Titanium Film Nanolayer by PECVD. In vitro Assessment of Surface Influence on Cell Adhesion during Initial Cell to Material Interaction

PubMed Central

Terriza, Antonia; Vilches-Pérez, José I.; González-Caballero, Juan L.; de la Orden, Emilio; Yubero, Francisco; Barranco, Angel; Gonzalez-Elipe, Agustín R.; Vilches, José; Salido, Mercedes

2014-01-01

New biomaterials for Guided Bone Regeneration (GBR), both resorbable and non-resorbable, are being developed to stimulate bone tissue formation. Thus, the in vitro study of cell behavior towards material surface properties turns a prerequisite to assess both biocompatibility and bioactivity of any material intended to be used for clinical purposes. For this purpose, we have developed in vitro studies on normal human osteoblasts (HOB®) HOB® osteoblasts grown on a resorbable Poly (lactide-co-glycolide) (PLGA) membrane foil functionalized by a very thin film (around 15 nm) of TiO2 (i.e., TiO2/PLGA membranes), designed to be used as barrier membrane. To avoid any alteration of the membranes, the titanium films were deposited at room temperature in one step by plasma enhanced chemical vapour deposition. Characterization of the functionalized membranes proved that the thin titanium layer completely covers the PLGA foils that remains practically unmodified in their interior after the deposition process and stands the standard sterilization protocols. Both morphological changes and cytoskeletal reorganization, together with the focal adhesion development observed in HOB osteoblasts, significantly related to TiO2 treated PLGA in which the Ti deposition method described has revealed to be a valuable tool to increase bioactivity of PLGA membranes, by combining cell nanotopography cues with the incorporation of bioactive factors. PMID:28788538

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. Copyright © 2016 Elsevier B.V. All rights reserved.

PLGA nanoparticles loaded with the antileishmanial saponin β-aescin: factor influence study and in vitro efficacy evaluation.

PubMed

Van de Ven, H; Vermeersch, M; Matheeussen, A; Vandervoort, J; Weyenberg, W; Apers, S; Cos, P; Maes, L; Ludwig, A

2011-11-25

Colloidal carriers are known to improve the therapeutic index of the conventional drugs in the treatment of visceral leishmaniasis (VL) by decreasing their toxicity whilst maintaining or increasing therapeutic efficacy. This paper describes the development of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for the antileishmanial saponin β-aescin. NPs were prepared by the W/O/W emulsification solvent evaporation technique and the influence of five preparation parameters on the NPs' size (Z(ave)), zeta potential and entrapment efficiency (EE%) was investigated using a 2(5-2) fractional factorial design. Cytotoxicity of aescin, aescin-loaded and blank PLGA NPs was evaluated in J774 macrophages and non-phagocytic MRC-5 cells, whereas antileishmanial activity was determined in the Leishmania infantum ex vivo model. The developed PLGA NPs were monodispersed with Z(ave)<500 nm and exhibited negative zeta potentials. The process variables 'surfactant primary emulsion', 'concentration aescin' and 'solvent evaporation rate' had a positive effect on EE%. Addition of Tween 80 to the inner aqueous phase rendered the primary emulsion more stable, which in its turn led to better saponin entrapment. The selectivity index (SI) towards the supporting host macrophages increased from 4 to 18 by treating the cells with aescin-loaded NPs instead of free β-aescin. In conclusion, the in vitro results confirmed our hypothesis. Copyright © 2011 Elsevier B.V. All rights reserved.

Synthesis of PLGA-Lipid Hybrid Nanoparticles for siRNA Delivery Using the Emulsion Method PLGA-PEG-Lipid Nanoparticles for siRNA Delivery.

PubMed

Wang, Lei; Griffel, Benjamin; Xu, Xiaoyang

2017-01-01

The effective delivery of small interfering RNA (siRNA) to tumor cells remains a challenge for applications in cancer therapy. The development of polymeric nanoparticles with high siRNA loading efficacy has shown great potential for cancer targets. Double emulsion solvent evaporation technique is a useful tool for encapsulation of hydrophilic molecules (e.g., siRNA). Here we describe a versatile platform for siRNA delivery based on PLGA-PEG-cationic lipid nanoparticles by using the double emulsion method. The resulting nanoparticles show high encapsulation efficiency for siRNA (up to 90%) and demonstrate effective downregulation of the target genes in vitro and vivo.

Estradiol-loaded PLGA nanoparticles for improving low bone mineral density of cancellous bone caused by osteoporosis: Application of enhanced charged nanoparticles with iontophoresis.

PubMed

Takeuchi, Issei; Kobayashi, Shiori; Hida, Yukari; Makino, Kimiko

2017-07-01

Postmenopausal osteoporosis among older women, which occurs by an ovarian hormone deficiency, is one of the major public health problems. 17 β-estradiol (E2) is used to prevent and treat this disease as a drug of hormone replacement therapy. In oral administration, E2 is significantly affected by first-pass hepatic metabolism, and high dose administration must be needed to obtain drug efficacy. Therefore, alternative administration route is needed, and we have focused on the transdermal drug delivery system. In this study, we have prepared E2-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles for osteoporosis by using a combination of an antisolvent diffusion method with preferential solvation. The average particle diameter of the nanoparticles was 110.0±41.0nm and the surface charge number density was 82 times higher than that of conventional E2-loaded PLGA nanoparticles. Therapeutic evaluation of E2-loaded PLGA nanoparticles was carried out using ovariectomized female rats. Therapeutic efficacy was evaluated to measure bone mineral density of cancellous bone using an X-ray CT system. When the E2-loaded PLGA nanoparticles were administrated once a week, bone mineral density was significantly higher than that of the non-treated group at 60days after the start of treatment. Also, in the group administered this nanoparticle twice a week, the bone mineral density increased significantly at 45days after the start of treatment. From these results, it was revealed that E2-loaded PLGA nanoparticles with iontophoresis were useful to recover bone mineral density of cancellous bone, and it was also suggested that they extend the dosing interval of E2. Copyright © 2017 Elsevier B.V. All rights reserved.

An injectable thermosensitive polymeric hydrogel for sustained release of Avastin® to treat posterior segment disease.

PubMed

Xie, Binbin; Jin, Ling; Luo, Zichao; Yu, Jing; Shi, Shuai; Zhang, Zhaoliang; Shen, Meixiao; Chen, Hao; Li, Xingyi; Song, Zongming

2015-07-25

Delivery of drugs, especially bioactive macromolecules such as proteins and nucleic acids, to the posterior segment is still a significant challenge for pharmaceutical scientists. In the present study, we developed an injectable thermosensitive polymeric hydrogel for sustained release of Avastin(®) to treat posterior segment disorders. The payload of Avastin(®) to poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) hydrogel did not influence its inherent sol-gel transition behavior, but shifted the sol-gel transition to a lower temperature. The resulting Avastin(®)/PLGA-PEG-PLGA hydrogels had a porous structure (pore size, 100 ∼ 150 μm) as determined by scanning electron microcopy (SEM), facilitating sustained Avastin(®) release over a period of up to 14 days in vitro. The PLGA-PEG-PLGA hydrogel was immediately formed in the vitreous humor after intravitreal injection, followed by slow clearance over an 8 week study period. The PLGA-PEG-PLGA hydrogel exhibited no apparent toxicity against retinal tissue, as indicated by the absence of inflammation, retinal necrosis, and stress responses, using optical coherence tomography (OCT) and histological/immunochemical analyses. Electrophysiology (ERG) examination also showed that the PLGA-PEG-PLGA hydrogel did not affect retinal function. In vivo pharmacokinetic studies indicated that the use of the PLGA-PEG-PLGA hydrogel greatly extended the release of Avastin(®) over time in the vitreous humor and retina after intravitreal injection. Together, these results demonstrated that the PLGA-PEG-PLGA hydrogel was a promising candidate for ocular drug delivery of Avastin(®)via intravitreal injection. Copyright © 2015 Elsevier B.V. All rights reserved.

Oral DNA vaccination of rainbow trout, Oncorhynchus mykiss (Walbaum), against infectious haematopoietic necrosis virus using PLGA [Poly(D,L-Lactic-Co-Glycolic Acid)] nanoparticles.

PubMed

Adomako, M; St-Hilaire, S; Zheng, Y; Eley, J; Marcum, R D; Sealey, W; Donahower, B C; Lapatra, S; Sheridan, P P

2012-03-01

A DNA vaccine against infectious haematopoietic necrosis virus (IHNV) is effective at protecting rainbow trout, Oncorhynchus mykiss, against disease, but intramuscular injection is required and makes the vaccine impractical for use in the freshwater rainbow trout farming industry. Poly (D,L-lactic-co-glycolic acid) (PLGA) is a U.S. Food and Drug Administration (FDA) approved polymer that can be used to deliver DNA vaccines. We evaluated the in vivo absorption of PLGA nanoparticles containing coumarin-6 when added to a fish food pellet. We demonstrated that rainbow trout will eat PLGA nanoparticle coated feed and that these nanoparticles can be detected in the epithelial cells of the lower intestine within 96 h after feeding. We also detected low levels of gene expression and anti-IHNV neutralizing antibodies when fish were fed or intubated with PLGA nanoparticles containing IHNV G gene plasmid. A virus challenge evaluation suggested a slight increase in survival at 6 weeks post-vaccination in fish that received a high dose of the oral vaccine, but there was no difference when additional fish were challenged at 10 weeks post-vaccination. The results of this study suggest that it is possible to induce an immune response using an orally delivered DNA vaccine, but the current system needs improvement. © 2012 Blackwell Publishing Ltd.

Porous glass makes effective substrate for ozone-sensing reagent

NASA Technical Reports Server (NTRS)

1965-01-01

Porous-glass substrate is used for absorption of a dye used in measuring the concentration of atmospheric ozone at high altitudes. This measurement is based on the chemiluminescence produced in the reaction between ozone and the dye, rhodamine B. The porous glass provides a large interstitial surface area which promotes this reaction.

Effect of Injection Molding Melt Temperatures on PLGA Craniofacial Plate Properties during In Vitro Degradation

PubMed Central

Fancello, Eduardo Alberto

2017-01-01

The purpose of this article is to present mechanical and physicochemical properties during in vitro degradation of PLGA material as craniofacial plates based on different values of injection molded temperatures. Injection molded plates were submitted to in vitro degradation in a thermostat bath at 37 ± 1°C by 16 weeks. The material was removed after 15, 30, 60, and 120 days; then bending stiffness, crystallinity, molecular weights, and viscoelasticity were studied. A significant decrease of molecular weight and mechanical properties over time and a difference in FT-IR after 60 days showed faster degradation of the material in the geometry studied. DSC analysis confirmed that the crystallization occurred, especially in higher melt temperature condition. DMA analysis suggests a greater contribution of the viscous component of higher temperature than lower temperature in thermomechanical behavior. The results suggest that physical-mechanical properties of PLGA plates among degradation differ per injection molding temperatures. PMID:29056968

Effect of Injection Molding Melt Temperatures on PLGA Craniofacial Plate Properties during In Vitro Degradation.

PubMed

de Melo, Liliane Pimenta; Salmoria, Gean Vitor; Fancello, Eduardo Alberto; Roesler, Carlos Rodrigo de Mello

2017-01-01

The purpose of this article is to present mechanical and physicochemical properties during in vitro degradation of PLGA material as craniofacial plates based on different values of injection molded temperatures. Injection molded plates were submitted to in vitro degradation in a thermostat bath at 37 ± 1°C by 16 weeks. The material was removed after 15, 30, 60, and 120 days; then bending stiffness, crystallinity, molecular weights, and viscoelasticity were studied. A significant decrease of molecular weight and mechanical properties over time and a difference in FT-IR after 60 days showed faster degradation of the material in the geometry studied. DSC analysis confirmed that the crystallization occurred, especially in higher melt temperature condition. DMA analysis suggests a greater contribution of the viscous component of higher temperature than lower temperature in thermomechanical behavior. The results suggest that physical-mechanical properties of PLGA plates among degradation differ per injection molding temperatures.

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

PubMed

Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-03-01

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

Transient inhibition of connective tissue infiltration and collagen deposition into porous poly(lactic-co-glycolic acid) discs.

PubMed

Love, Ryan J; Jones, Kim S

2013-12-01

Connective tissue rapidly proliferates on and around biomaterials implanted in vivo, which impairs the function of the engineered tissues, biosensors, and devices. Glucocorticoids can be utilized to suppress tissue ingrowth, but can only be used for a limited time because they nonselectively arrest cell proliferation in the local environment. The present study examined use of a prolyl-4-hydroxylase inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), to suppress connective tissue ingrowth in porous PLGA discs implanted in the peritoneal cavity for 28 days. The prolyl-4-hydroxylase inhibitor was found to be effective at inhibiting collagen deposition within and on the outer surface of the disc, and also limited connective tissue ingrowth, but not to the extent of glucocorticoid inhibition. Finally, it was discovered that 1,4-DPCA suppressed Scavenger Receptor A expression on a macrophage-like cell culture, which may account for the drug's ability to limit connective tissue ingrowth in vivo. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Effect of Polymer Porosity on Aqueous Self-Healing Encapsulation of Proteins in PLGA Microspheres

PubMed Central

Reinhold, Samuel E.

2014-01-01

Self-healing (SH) poly(lactic-co-glycolic acid) (PLGA) microspheres are a unique class of functional biomaterials capable of microencapsulating process-sensitive proteins by simple mixing and heating the drug-free polymer in aqueous protein solution. Drug-free SH microspheres of PLGA 50/50 with percolating pore networks of varying porosity (ε = 0.49–73) encapsulate increasing lysozyme (~1–10% w/w) with increasing ε, with typically ~20–25% pores estimated assessible to entry by the enzyme from the external solution. Release kinetics of lysozyme under physiological conditions is continuous over > 2 weeks and most strongly influenced by ε and protein loading before reaching a lag phase until 28 days at the study completion. Recovered enzyme after release is typically predominantly monomeric and active. Formulations containing acid-neutralizing MgCO3 at >4.3% exhibit >97% monomeric and active protein after the release with full mass balance recovery. Hence, control of SH polymer ε is a key parameter to development of this new class of biomaterials. PMID:24285573

Coating and release of an anti-inflammatory hormone from PLGA microspheres for tissue engineering.

PubMed

Go, Dewi P; Palmer, Jason A; Gras, Sally L; O'Connor, Andrea J

2012-02-01

Many biomaterials used in tissue engineering cause a foreign body response in vivo, which left untreated can severely reduce the effectiveness of tissue regeneration. In this study, an anti-inflammatory hormone α-melanocyte stimulating hormone (α-MSH) was physically adsorbed to the surface of biodegradable poly (lactic-co-glycolic) acid (PLGA) microspheres to reduce inflammatory responses to this material. The stability and adsorption isotherm of peptide binding were characterized. The peptide secondary structure was not perturbed by the adsorption and subsequent desorption process. The α-MSH payload was released over 72 h and reduced the expression of the inflammatory cytokine, Tumor necrosis factor-α (TNF-α) in lipopolysaccharide activated RAW 264.7 macrophage cells, indicating that the biological activity of α-MSH was preserved. α-MSH coated PLGA microspheres also appeared to reduce the influx of inflammatory cells in a subcutaneous implantation model in rats. This study demonstrates the potential of α-MSH coatings for anti-inflammatory delivery and this approach may be applied to other tissue engineering applications. Copyright © 2011 Wiley Periodicals, Inc.

Biodegradable Nanoparticles of mPEG-PLGA-PLL Triblock Copolymers as Novel Non-Viral Vectors for Improving siRNA Delivery and Gene Silencing

PubMed Central

Du, Jing; Sun, Ying; Shi, Qiu-Sheng; Liu, Pei-Feng; Zhu, Ming-Jie; Wang, Chun-Hui; Du, Lian-Fang; Duan, You-Rong

2012-01-01

Degradation of mRNA by RNA interference is one of the most powerful and specific mechanisms for gene silencing. However, insufficient cellular uptake and poor stability have limited its usefulness. Here, we report efficient delivery of siRNA via the use of biodegradable nanoparticles (NPs) made from monomethoxypoly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly-l-lysine (mPEG-PLGA-PLL) triblock copolymers. Various physicochemical properties of mPEG-PLGA-PLL NPs, including morphology, size, surface charge, siRNA encapsulation efficiency, and in vitro release profile of siRNA from NPs, were characterized by scanning electron microscope, particle size and zeta potential analyzer, and high performance liquid chromatography. The levels of siRNA uptake and targeted gene inhibition were detected in human lung cancer SPC-A1-GFP cells stably expressing green fluorescent protein. Examination of the cultured SPC-A1-GFP cells with fluorescent microscope and flow cytometry showed NPs loading Cy3-labeled siRNA had much higher intracellular siRNA delivery efficiencies than siRNA alone and Lipofectamine-siRNA complexes. The gene silencing efficiency of mPEG-PLGA-PLL NPs was higher than that of commercially available transfecting agent Lipofectamine while showing no cytotoxicity. Thus, the current study demonstrates that biodegradable NPs of mPEG-PLGA-PLL triblock copolymers can be potentially applied as novel non-viral vectors for improving siRNA delivery and gene silencing. PMID:22312268

Bioceramic/poly (glycolic)-poly (lactic acid) composite induces mineralized barrier after direct capping of rat tooth pulp tissue.

PubMed

Gala-Garcia, Alfonso; Teixeira, Karina Imaculada Rosa; Wykrota, Francisco Henrique Lana; Sinisterra, Rubén Dario; Cortés, Maria Esperanza

2010-01-01

The aim of this study was to observe the histopathological pulp response following direct pulp capping of mechanically exposed teeth in rats with a composite of beta-tricalcium phosphate-hydroxyapatite bioceramic (BC) and poly (glycolic)-poly (lactic acid) (PLGA) material or a calcium hydroxide [Ca(OH)2] material, compared to BC alone and a negative control of water. Pulp of the maxillary molars was exposed, followed by capping with the experimental material. The pulpal tissue response was assessed post-operatively at 1, 7, 14 and 30 d, followed by histological analysis. The Ca(OH)2 group exhibited severe acute inflammatory cell infiltration at day 14. However after 30 d, a new hard tissue with macro porous obliteration of the pulp chamber and a characteristic necrotic area had appeared. BC and Ca(OH)2 capping were associated with moderate inflammation and dentinal bridge similar. Meanwhile, in the BC/PLGA composite group, there was moderate inflammatory infiltrate and formation of a dense and complete dentinal bridge. In conclusion, the BC/PLGA composite material showed a large zone of tertiary dentin, and effectively reorganized the dentin-pulp complex.

PLGA particulate subunit tuberculosis vaccines promote humoral and Th17 responses but do not enhance control of Mycobacterium tuberculosis infection

PubMed Central

Parumasivam, Thaigarajan; Chan, John Gar Yan; Lin, Leon C. W.; Flórido, Manuela; West, Nicholas P.; Chan, Hak-Kim; Britton, Warwick J.

2018-01-01

Tuberculosis places a staggering burden on human health globally. The new World Health Organisation End-TB Strategy has highlighted the urgent need for more effective TB vaccines to improve control of the disease. Protein-based subunit vaccines offer potential as safe and effective generators of protective immunity, and the use of particulate vaccine formulation and delivery by the pulmonary route may enhance local immunogenicity. In this study, novel particulate subunit vaccines were developed utilising biodegradable poly(lactic-co-glycolic acid) (PLGA) slow-release particles as carriers for the Mycobacterium tuberculosis lipoprotein MPT83, together with the adjuvants trehalose-dibehenate (TDB) or Monophosphoryl lipid A (MPL). Following delivery by the pulmonary or subcutaneous routes, the immunogenicity and protective efficacy of these vaccines were assessed in a murine model of M. tuberculosis infection. When delivered peripherally, these vaccines induced modest, antigen-specific Th1 and Th17 responses, but strong anti-MPT83 antibody responses. Mucosal delivery of the PLGA(MPT83) vaccine, with or without TDB, increased antigen-specific Th17 responses in the lungs, however, PLGA-encapsulated vaccines did not provide protection against M. tuberculosis challenge. By contrast, peripheral delivery of DDA liposomes containing MPT83 and TDB or MPL, stimulated both Th1 and Th17 responses and generated protection against M. tuberculosis challenge. Therefore, PLGA-formulated vaccines primarily stimulate strong humoral immunity, or Th17 responses if used mucosally, and may be a suitable carrier for vaccines against extracellular pathogens. This study emphasises the critical nature of the vaccine carrier, adjuvant and route of delivery for optimising vaccine efficacy against TB. PMID:29554138

Injectable biodegradable temperature-responsive PLGA-PEG-PLGA copolymers: synthesis and effect of copolymer composition on the drug release from the copolymer-based hydrogels.

PubMed

Qiao, Mingxi; Chen, Dawei; Ma, Xichen; Liu, Yanjun

2005-04-27

Injectable biodegradable temperature-responsive poly(DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with DL-lactide/glycolide molar ratio ranging from 6/1 to 15/l were synthesized from monomers of DL-lactide, glycolide and polyethylene glycol and characterized by 1H NMR. The resulting copolymers are soluble in water to form free flowing fluid at room temperature but become hydrogels at body temperature. The hydrophobicity of the copolymer increased with the increasing of DL-lactide/glycolide molar ratio. In vitro dissolution studies with two different hydrophobic drugs (5-fluorouracil and indomethacin) were performed to study the effect of DL-lactide/glycolide molar ratio on drug release and to elucidate drug release mechanism. The release mechanism for hydrophilic 5-fluorouracil was diffusion-controlled, while hydrophobic indomethacin showed an biphasic profile comprising of an initial diffusion-controlled stage followed by the hydrogel erosion-dominated stage. The effect of DL-lactide/glycolide molar ratio on drug release seemed to be dependent on the drug release mechanism. It has less effect on the drug release during the diffusion-controlled stage, but significantly affected drug release during the hydrogel erosion-controlled stage. Compared with ReGel system, the synthesized copolymers showed a higher gelation temperature and longer period of drug release. The copolymers can solubilize the hydrophobic indomethacin and the solubility (13.7 mg/ml) was increased 3425-fold compared to that in water (4 microg/ml, 25 degrees C). Two methods of physical mixing method and solvent evaporation method were used for drug solubilization and the latter method showed higher solubilization efficiency.

Optical performance of hybrid porous silicon-porous alumina multilayers

NASA Astrophysics Data System (ADS)

Cencha, L. G.; Antonio Hernández, C.; Forzani, L.; Urteaga, R.; Koropecki, R. R.

2018-05-01

In this work, we study the optical response of structures involving porous silicon and porous alumina in a multi-layered hybrid structure. We performed a rational design of the optimal sequence necessary to produce a high transmission and selective filter, with potential applications in chemical and biosensors. The combination of these porous materials can be used to exploit its distinguishing features, i.e., high transparency of alumina and high refractive index of porous silicon. We assembled hybrid microcavities with a central porous alumina layer between two porous silicon Bragg reflectors. In this way, we constructed a Fabry-Perot resonator with high reflectivity and low absorption that improves the quality of the filter compared to a microcavity built only with porous silicon or porous alumina. We explored a simpler design in which one of the Bragg reflectors is replaced by the aluminium that remains bound to the alumina after its fabrication. We theoretically explored the potential of the proposal and its limitations when considering the roughness of the layers. We found that the quality of a microcavity made entirely with porous silicon shows a limit in the visible range due to light absorption. This limitation is overcome in the hybrid scheme, with the roughness of the layers determining the ultimate quality. Q-factors of 220 are experimentally obtained for microcavities supported on aluminium, while Q-factors around 600 are reached for microcavities with double Bragg reflectors, centred at 560 nm. This represents a four-fold increase with respect to the optimal porous silicon microcavity at this wavelength.

Protective efficacy of cationic-PLGA microspheres loaded with DNA vaccine encoding the sip gene of Streptococcus agalactiae in tilapia.

PubMed

Ma, Yan-Ping; Ke, Hao; Liang, Zhi-Ling; Ma, Jiang-Yao; Hao, Le; Liu, Zhen-Xing

2017-07-01

Streptococcus agalactiae (S. agalactiae) is an important fish pathogen, which has received more attention in the past decade due to the increasing economic losses in the tilapia industry worldwide. As existing effective vaccines of S. agalactiae in fish have obvious disadvantage, to select immunoprotective antigens and package materials would undoubtedly contribute to the development of novel oral vaccines. In the present study, surface immunogenic protein (sip) was selected from the S. agalactiae serovar I a genomes as immunogenic protein in DNA vaccine form with cationic chitosan and biodegradable and biocompatible PLGA. The pcSip plasmid in cationic-PLGA was successfully expressed in tissues of immunized tilapia and the immunogenicity was assessed in tilapia challenge model. A significant increase was observed in the cytokine levels of IL-1β, TNF-α, CC1, CC2 in spleen and kidney tissues. Furthermore, immunized tilapia conferred different levels of protection against challenge with a lethal dose of highly virulent serovar I a S. agalactiae. Our results indicated that the pcSip plasmid in cationic-PLGA induced high level of antibodies and protection against S. agalactiae infection, could be effective oral DNA vaccine candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.

PLGA nanoparticles for the oral delivery of 5-Fluorouracil using high pressure homogenization-emulsification as the preparation method and in vitro/in vivo studies.

PubMed

Li, XueMing; Xu, YuanLong; Chen, GuoGuang; Wei, Ping; Ping, QiNeng

2008-01-01

The objective of the present study was to incorporate the hydrophilic anti-cancer drug 5-Fluorouracil(5-FU) into poly(lactide-co-glycolide) (PLGA) nanoparticles(NP) to improve the oral bioavailability. Owing to the high solubility of 5-FU in basic water, the water-in-oil-in-water (w/o/w) emulsification process has been chosen as one of the most appropriate method for the encapsulation of 5-FU, and the ammonia solution was used as the inner aqueous phase solvent to increase the solubility of 5-FU. In order to reach submicron size as well as increasing the grade of monodispersity compared to previous preparation techniques, we prepared 5-FU loaded PLGA-NP by a high-pressure emulsification-solvent evaporation process. The PLGA-NPs were characterized with respect to their morphology, particle size, size distribution, 5-FU encapsulation efficiency, in vitro and in vivo studies in rats. In vitro release of 5-FU from nanoparticles appeared to have two components with an initial rapid release due to the surface associated drug and followed by a slower exponential release of 5-FU, which was dissolved in the core. The in vivo research was studied in male Sprague-Dawley rats after an oral 5-FU dose of 45 mg/kg. Single oral administration of 5-FU loaded PLGA-NP to rats produced bioavailability, which was statistically higher than 5-FU solution as negative control. And the MRT (mean residence time) of 5-FU loaded PLGA-NP was significantly (P < 0.05) modified. Thus, it is possible to design a controlled drug delivery system for oral 5-FU delivery, improving therapy efficiency by possible reduction of time intervals between peroral administrations and reduction of local gastrointestinal side effects.

Experimental Simulations of Large-Scale Collisions

NASA Technical Reports Server (NTRS)

Housen, Kevin R.

2002-01-01

This report summarizes research on the effects of target porosity on the mechanics of impact cratering. Impact experiments conducted on a centrifuge provide direct simulations of large-scale cratering on porous asteroids. The experiments show that large craters in porous materials form mostly by compaction, with essentially no deposition of material into the ejecta blanket that is a signature of cratering in less-porous materials. The ratio of ejecta mass to crater mass is shown to decrease with increasing crater size or target porosity. These results are consistent with the observation that large closely-packed craters on asteroid Mathilde appear to have formed without degradation to earlier craters.

Rapid process for producing transparent, monolithic porous glass

DOEpatents

Coronado, Paul R [Livermore, CA

2006-02-14

A process for making transparent porous glass monoliths from gels. The glass is produced much faster and in much larger sizes than present technology for making porous glass. The process reduces the cost of making large porous glass monoliths because: 1) the process does not require solvent exchange nor additives to the gel to increase the drying rates, 2) only moderate temperatures and pressures are used so relatively inexpensive equipment is needed, an 3) net-shape glass monoliths are possible using this process. The process depends on the use of temperature to control the partial pressure of the gel solvent in a closed vessel, resulting in controlled shrinking during drying.

Impacts into porous asteroids

NASA Astrophysics Data System (ADS)

Housen, Kevin R.; Sweet, William J.; Holsapple, Keith A.

2018-01-01

Many small bodies in the solar system have bulk density well below the solid density of the constituent mineral grains in their meteorite counterparts. Those low-density bodies undoubtedly have significant porosity, which is a key factor that affects the formation of impact craters. This paper summarizes the results of lab experiments in which materials with porosity ranging from 43% to 96% were impacted at ∼1800 m/s. The experiments were performed on a geotechnical centrifuge, in order to reproduce the lithostatic overburden stress and ejecta ballistics that occur in large-scale cratering events on asteroids or planetary satellites. Experiments performed at various accelerations, up to 514G, simulate the outcomes of impacts at size scales up to several tens of km in diameter. Our experiments show that an impact into a highly porous cohesionless material generates a large ovoid-shaped cavity, due to crushing by the outgoing shock. The cavity opens up to form a transient crater that grows until the material flow is arrested by gravity. The cavity then collapses to form the final crater. During collapse, finely crushed material that lines the cavity wall is carried down and collected in a localized region below the final crater floor. At large simulated sizes (high accelerations), most of the crater volume is formed by compaction, because growth of the transient crater is quickly arrested. Nearly all ejected material falls back into the crater, leaving the crater without an ejecta blanket. We find that such compaction cratering and suppression of the ejecta blankets occur for large craters on porous bodies when the ratio of the lithostatic stress at one crater depth to the crush strength of the target exceeds ∼0.005. The results are used to identify small solar system bodies on which compaction cratering likely occurs. A model is developed that gives the crater size and ejecta mass that would result for a specified impact into a porous object.

Bone repair by cell-seeded 3D-bioplotted composite scaffolds made of collagen treated tricalciumphosphate or tricalciumphosphate-chitosan-collagen hydrogel or PLGA in ovine critical-sized calvarial defects.

PubMed

Haberstroh, Kathrin; Ritter, Kathrin; Kuschnierz, Jens; Bormann, Kai-Hendrik; Kaps, Christian; Carvalho, Carlos; Mülhaupt, Rolf; Sittinger, Michael; Gellrich, Nils-Claudius

2010-05-01

The aim of this study was to investigate the osteogenic effect of three different cell-seeded 3D-bioplotted scaffolds in a ovine calvarial critical-size defect model. The choice of scaffold-materials was based on their applicability for 3D-bioplotting and respective possibility to produce tailor-made scaffolds for the use in cranio-facial surgery for the replacement of complex shaped boneparts. Scaffold raw-materials are known to be osteoinductive when being cell-seeded [poly(L-lactide-co-glycolide) (PLGA)] or having components with osteoinductive properties as tricalciumphosphate (TCP) or collagen (Col) or chitosan. The scaffold-materials PLGA, TCP/Col, and HYDR (TCP/Col/chitosan) were cell-seeded with osteoblast-like cells whether gained from bone (OLB) or from periost (OLP). In a prospective and randomized design nine sheep underwent osteotomy to create four critical-sized calvarial defects. Three animals each were assigned to the HYDR-, the TCP/Col-, or the PLGA-group. In each animal, one defect was treated with a cell-free, an OLB- or OLP-seeded group-specific scaffold, respectively. The fourth defect remained untreated as control (UD). Fourteen weeks later, animals were euthanized for histo-morphometrical analysis of the defect healing. OLB- and OLP-seeded HYDR and OLB-seeded TCP/Col scaffolds significantly increased the amount of newly formed bone (NFB) at the defect bottom and OLP-seeded HYDR also within the scaffold area, whereas PLGA-scaffolds showed lower rates. The relative density of NFB was markedly higher in the HYDR/OLB group compared to the corresponding PLGA group. TCP/Col had good stiffness to prepare complex structures by bioplotting but HYDR and PLGA were very soft. HYDR showed appropriate biodegradation, TCP/Col and PLGA seemed to be nearly undegraded after 14 weeks. 3D-bioplotted, cell-seeded HYDR and TCP/Col scaffolds increased the amount of NFB within ovine critical-size calvarial defects, but stiffness, respectively, biodegradation of

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. Copyright 2009 Elsevier B.V. All rights reserved.

The Evaluation of the Possibilities of Using PLGA Co-Polymer and Its Composites with Carbon Fibers or Hydroxyapatite in the Bone Tissue Regeneration Process – in Vitro and in Vivo Examinations

PubMed Central

Cieślik, Magdalena; Mertas, Anna; Morawska-Chochólł, Anna; Sabat, Daniel; Orlicki, Rajmund; Owczarek, Aleksander; Król, Wojciech; Cieślik, Tadeusz

2009-01-01

Synthetic polymers belonging to the aliphatic polyester group have become highly promising biomaterials for reconstructive medicine. The purpose of the present work is a biological evaluation of lactide-glycolide co-polymer (PLGA) and its composites with carbon fibers (PLGA+CF) or hydroxyapatite (PLGA+HA). The cytotoxicity of the evaluated materials towards hFOB 1.19 human osteoblast-like cells was assessed. Moreover, during the one-year contact of the assessed materials with living osseous tissue, the progress of bone formation was analyzed and the accompanying process of the materials’ degradation was evaluated. The materials under evaluation proved to be biocompatible. PMID:19742134

Development of a novel CsA-PLGA drug delivery system based on a glaucoma drainage device for the prevention of postoperative fibrosis.

PubMed

Dai, Zhaoxing; Yu, Xiaobo; Hong, Jiaxu; Liu, Xi; Sun, Jianguo; Sun, Xinghuai

2016-09-01

The formation of a scar after glaucoma surgery often leads to unsuccessful control of intraocular pressure, and should be prevented by using a variety of methods. We designed and developed a novel drug delivery system (DDS) comprising cyclosporine A (CsA) and poly(lactic-co-glycolic acid) (PLGA) based on a glaucoma drainage device (GDD) that can continuously release CsA to prevent postoperative fibrosis following glaucoma surgery. The CsA@PLGA@GDD DDS was observed by field emission scanning electron microscopy and revealed an asymmetric pore structure. Thermogravimetric analysis was performed to measure the weight loss and evaluate the thermal stability of the CsA@PLGA@GDD DDS. The in vitro drug release profile of the DDS was studied using high performance liquid chromatography, which confirmed that the DDS released CsA at a stable rate and maintained adequate CsA concentrations for a relatively long time. The biocompatibility of the DDS and the inhibitory effects on the postoperative fibrosis were investigated in vitro using rabbit Tenon's fibroblasts. The in vivo safety and efficacy of the DDS were examined by implanting the DDS into Tenon's capsules in New Zealand rabbits. Bleb morphology, intraocular pressure, anterior chamber reactions, and anterior chamber angiography were studied at a series of set times. The DDS kept the filtration pathway unblocked for a longer time compared with the control GDD. The results indicate that the CsA@PLGA@GDD DDS represents a safe and effective strategy for preventing scar formation after glaucoma surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

PLGA-soya lecithin based micelles for enhanced delivery of methotrexate: Cellular uptake, cytotoxic and pharmacokinetic evidences.

PubMed

Singh, Anupama; Thotakura, Nagarani; Kumar, Rajendra; Singh, Bhupinder; Sharma, Gajanand; Katare, Om Prakash; Raza, Kaisar

2017-02-01

Biocompatible and biodegradable polymers like PLGA have revolutionized the drug delivery approaches. However, poor drug loading and substantially high lipophilicity, pave a path for further tailing of this promising agent. In this regard, PLGA was feathered with biocompatible phospholipid and polymeric micelles were developed for delivery of Methotrexate (MTX) to cancer cells. The nanocarriers (114.6nm±5.5nm) enhanced the cytotoxicity of MTX by 2.13 folds on MDA-MB-231 cells. Confocal laser scanning microscopy confirmed the increased intracellular delivery. The carrier decreased the protein binding potential and enhanced the bioavailable fraction of MTX. Pharmacokinetic studies vouched substantial enhancement in AUC and bioresidence time, promising an ideal carrier to effectively deliver the drug to the site of action. The developed nanocarriers offer potential to deliver the drug in the interiors of cancer cells in an effective manner for improved therapeutic action. Copyright © 2016 Elsevier B.V. All rights reserved.

Poly(lactide-co-glycolide acid)/biphasic calcium phosphate composite coating on a porous scaffold to deliver simvastatin for bone tissue engineering.

PubMed

Sadiasa, Alexander; Kim, Min Sung; Lee, Byong Taek

2013-09-01

In this study, simvastatin (SIM) drug incorporated poly(D,L-lactic-co-glycolide) (PLGA)/biphasic calcium phosphate (BCP) composite material (SPB) was coated on the BCP/ZrO2 (SPB-BCP/ZrO2) scaffold to enhance the mechanical and bioactive properties of the BCP/ZrO2 scaffold for bone engineering applications. The composite coating was prepared by combining different ratios of PLGA and BCP (1:2, 1:1, 2:1). After completion of the coating process, the compressive strength of the scaffolds was shown to increase with an increase in PLGA concentration from 8.5 ± 0.52 MPa for the SPB1-BCP/ZrO2 (1:2) to 11 ± 0.65 MPa for SPB3-BCP/ZrO2 (2:1) scaffolds when PLGA concentration was increased. Furthermore, the increase of PLGA in the coating composition corresponds to a decrease in porosity, degradation rate and weight loss of the scaffolds after 4 weeks. SIM release study demonstrated sustained release of the drug for the three kinds of scaffolds with improved biocompatibility. The increase of PLGA concentration also resulted in a lower release rate of SIM. Thus, the lower release rate of SIM brought upon by the increase of PLGA concentration further enhanced the performance of the scaffold in vitro making it a promising approach in the field of bone tissue regeneration.

Isocratic and gradient impedance plot analysis and comparison of some recently introduced large size core-shell and fully porous particles.

PubMed

Vanderheyden, Yoachim; Cabooter, Deirdre; Desmet, Gert; Broeckhoven, Ken

2013-10-18

The intrinsic kinetic performance of three recently commercialized large size (≥4μm) core-shell particles packed in columns with different lengths has been measured and compared with that of standard fully porous particles of similar and smaller size (5 and 3.5μm, respectively). The kinetic performance is compared in both absolute (plot of t0 versus the plate count N or the peak capacity np for isocratic and gradient elution, respectively) and dimensionless units. The latter is realized by switching to so-called impedance plots, a format which has been previously introduced (as a plot of t0/N(2) or E0 versus Nopt/N) and has in the present study been extended from isocratic to gradient elution (where the impedance plot corresponds to a plot of t0/np(4) versus np,opt(2)/np(2)). Both the isocratic and gradient impedance plot yielded a very similar picture: the clustered impedance plot curves divide into two distinct groups, one for the core-shell particles (lowest values, i.e. best performance) and one for the fully porous particles (highest values), confirming the clear intrinsic kinetic advantage of core-shell particles. If used around their optimal flow rate, the core-shell particles displayed a minimal separation impedance that is about 40% lower than the fully porous particles. Even larger gains in separation speed can be achieved in the C-term regime. Copyright © 2013 Elsevier B.V. All rights reserved.

MAPLE deposition of PLGA:PEG films for controlled drug delivery: Influence of PEG molecular weight

NASA Astrophysics Data System (ADS)

Paun, Irina Alexandra; Moldovan, Antoniu; Luculescu, Catalin Romeo; Staicu, Angela; Dinescu, Maria

2012-09-01

Implantable devices consisting of indomethacin (INC) cores coated with poly(lactide-co-glycolide):polyethylene glycol films (i.e. PLGA:PEG films) deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) were produced. To predict their behavior after implantation inside the body, the implants were studied in vitro, in media similar with those encountered inside the body (phosphate buffered saline (PBS) pH 7.4 and blood). The influence of the molecular weight of PEG (i.e. low (1450 Da) versus high (10 kDa) molecular weights) on the characteristics of the implants was investigated, in terms of morphology, blood compatibility and kinetics of the drug release. The use of PEG of high molecular weight resulted in larger pores on the implants surfaces, enhanced blood compatibility of the implants and higher drug delivery rates. For both molecular weights PEGs, sustained release of INC was maintained over a three weeks interval. Theoretical fitting of the drug release data with Higuchi's model indicated that the INC was released mainly by diffusion, most probably through the pores formed in PLGA:PEG films during PBS immersion.

Penetration and distribution of PLGA nanoparticles in the human skin treated with microneedles.

PubMed

Zhang, Wei; Gao, Jing; Zhu, Quangang; Zhang, Min; Ding, Xueying; Wang, Xiaoyu; Hou, Xuemei; Fan, Wei; Ding, Baoyue; Wu, Xin; Wang, Xiying; Gao, Shen

2010-12-15

This study was designed to investigate the penetration and the distribution of poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles in the human skin treated with microneedles. Fluorescent nanoparticles were prepared to indicate the transdermal transport process of the nanoparticles. Permeation study was performed on Franz-type diffusion cells in vitro. The distribution of nanoparticles was visualized by confocal laser scanning microscopy (CLSM) and quantified by high performance liquid chromatography (HPLC). CLSM images showed that nanoparticles were delivered into the microconduits created by microneedles and permeated into the epidermis and the dermis. The quantitative determination showed that (i) the permeation of nanoparticles into the skin was enhanced by microneedles, but no nanoparticle reached the receptor solution; (ii) much more nanoparticles deposited in the epidermis than those in the dermis; (iii) the permeation was in a particle size-dependent manner; and (iv) the permeation increased with the nanoparticle concentration increasing until a limit value was reached. These results suggested that microneedles could enhance the intradermal delivery of PLGA nanoparticles. The biodegradable nanoparticles would sustain drug release in the skin and supply the skin with drug over a prolonged period. This strategy would prove to be useful for topical drug administration. Copyright © 2010 Elsevier B.V. All rights reserved.

Continuous Purification of Colloidal Quantum Dots in Large-Scale Using Porous Electrodes in Flow Channel.

PubMed

Lim, Hosub; Woo, Ju Young; Lee, Doh C; Lee, Jinkee; Jeong, Sohee; Kim, Duckjong

2017-02-27

Colloidal quantum dots (QDs) afford huge potential in numerous applications owing to their excellent optical and electronic properties. After the synthesis of QDs, separating QDs from unreacted impurities in large scale is one of the biggest issues to achieve scalable and high performance optoelectronic applications. Thus far, however, continuous purification method, which is essential for mass production, has rarely been reported. In this study, we developed a new continuous purification process that is suitable to the mass production of high-quality QDs. As-synthesized QDs are driven by electrophoresis in a flow channel and captured by porous electrodes and finally separated from the unreacted impurities. Nuclear magnetic resonance and ultraviolet/visible/near-infrared absorption spectroscopic data clearly showed that the impurities were efficiently removed from QDs with the purification yield, defined as the ratio of the mass of purified QDs to that of QDs in the crude solution, up to 87%. Also, we could successfully predict the purification yield depending on purification conditions with a simple theoretical model. The proposed large-scale purification process could be an important cornerstone for the mass production and industrial use of high-quality QDs.

Continuous Purification of Colloidal Quantum Dots in Large-Scale Using Porous Electrodes in Flow Channel

NASA Astrophysics Data System (ADS)

Lim, Hosub; Woo, Ju Young; Lee, Doh Chang; Lee, Jinkee; Jeong, Sohee; Kim, Duckjong

2017-11-01

Colloidal Quantum dots (QDs) afford huge potential in numerous applications owing to their excellent optical and electronic properties. After the synthesis of QDs, separating QDs from unreacted impurities in large scale is one of the biggest issues to achieve scalable and high performance optoelectronic applications. Thus far, however, continuous purification method, which is essential for mass production, has rarely been reported. In this study, we developed a new continuous purification process that is suitable to the mass production of high-quality QDs. As-synthesized QDs are driven by electrophoresis in a flow channel and captured by porous electrodes and finally separated from the unreacted impurities. Nuclear magnetic resonance and ultraviolet/visible/near-infrared absorption spectroscopic data clearly showed that the impurities were efficiently removed from QDs with the purification yield, defined as the ratio of the mass of purified QDs to that of QDs in the crude solution, up to 87%. Also, we could successfully predict the purification yield depending on purification conditions with a simple theoretical model. The proposed large-scale purification process could be an important cornerstone for the mass production and industrial use of high-quality QDs.

Porous organic cages

NASA Astrophysics Data System (ADS)

Tozawa, Tomokazu; Jones, James T. A.; Swamy, Shashikala I.; Jiang, Shan; Adams, Dave J.; Shakespeare, Stephen; Clowes, Rob; Bradshaw, Darren; Hasell, Tom; Chong, Samantha Y.; Tang, Chiu; Thompson, Stephen; Parker, Julia; Trewin, Abbie; Bacsa, John; Slawin, Alexandra M. Z.; Steiner, Alexander; Cooper, Andrew I.

2009-12-01

Porous materials are important in a wide range of applications including molecular separations and catalysis. We demonstrate that covalently bonded organic cages can assemble into crystalline microporous materials. The porosity is prefabricated and intrinsic to the molecular cage structure, as opposed to being formed by non-covalent self-assembly of non-porous sub-units. The three-dimensional connectivity between the cage windows is controlled by varying the chemical functionality such that either non-porous or permanently porous assemblies can be produced. Surface areas and gas uptakes for the latter exceed comparable molecular solids. One of the cages can be converted by recrystallization to produce either porous or non-porous polymorphs with apparent Brunauer-Emmett-Teller surface areas of 550 and 23m2g-1, respectively. These results suggest design principles for responsive porous organic solids and for the modular construction of extended materials from prefabricated molecular pores.

Two-layer membranes of calcium phosphate/collagen/PLGA nanofibres: in vitro biomineralisation and osteogenic differentiation of human mesenchymal stem cells

NASA Astrophysics Data System (ADS)

Hild, Nora; Schneider, Oliver D.; Mohn, Dirk; Luechinger, Norman A.; Koehler, Fabian M.; Hofmann, Sandra; Vetsch, Jolanda R.; Thimm, Benjamin W.; Müller, Ralph; Stark, Wendelin J.

2011-02-01

The present study evaluates the in vitro biomedical performance of an electrospun, flexible, anisotropic bilayer with one layer containing a collagen to mineral ratio similar to that in bone. The double membrane consists of a poly(lactide-co-glycolide) (PLGA) layer and an amorphous calcium phosphate (a-CaP)/collagen (Col)/PLGA layer. In vitro biomineralisation and a cell culture study with human mesenchymal stem cells (hMSC) were conducted to characterise such membranes for possible application as biomaterials. Nanofibres with different a-CaP/Col/PLGA compositions were synthesised by electrospinning to mimic the actual composition of bone tissue. Immersion in simulated body fluid and in cell culture medium resulted in the deposition of a hydroxyapatite layer. Incubation of hMSC for 4 weeks allowed for assessment of the proliferation and osteogenic differentiation of the cells on both sides of the double membrane. Confocal laser scanning microscopy was used to observe the proper adhesion of the cells. Calcium and collagen content was proven by Alizarin red S and Sirius red assays. Acute cytotoxic effects of the nanoparticles or the chemicals used in the scaffold preparation could be excluded based on viability assays (alamarBlue and alkaline phosphatase activity). The findings suggest possible application of such double membranes is in treatment of bone defects with complex geometries as wound dressing material.The present study evaluates the in vitro biomedical performance of an electrospun, flexible, anisotropic bilayer with one layer containing a collagen to mineral ratio similar to that in bone. The double membrane consists of a poly(lactide-co-glycolide) (PLGA) layer and an amorphous calcium phosphate (a-CaP)/collagen (Col)/PLGA layer. In vitro biomineralisation and a cell culture study with human mesenchymal stem cells (hMSC) were conducted to characterise such membranes for possible application as biomaterials. Nanofibres with different a-CaP/Col/PLGA

Study of the Effect of Turbulence and Large Obstacles on the Evaporation from Bare Soil Surface through Coupled Free-flow and Porous-medium Flow Model

NASA Astrophysics Data System (ADS)

Gao, B.; Smits, K. M.

2017-12-01

Evaporation is a strongly coupled exchange process of mass, momentum and energy between the atmosphere and the soil. Several mechanisms influence evaporation, such as the atmospheric conditions, the structure of the soil surface, and the physical properties of the soil. Among the previous studies associated with evaporation modeling, most efforts use uncoupled models which simplify the influences of the atmosphere and soil through the use of resistance terms. Those that do consider the coupling between the free flow and porous media flow mainly consider flat terrain with grain-scale roughness. However, larger obstacles, which may form drags or ridges allowing normal convective air flow through the soil, are common in nature and may affect the evaporation significantly. Therefore, the goal of this work is to study the influence of large obstacles such as wavy surfaces on the flow behavior within the soil and exchange processes to the atmosphere under turbulent free-flow conditions. For simplicity, the soil surface with large obstacles are represented by a simple wavy surface. To do this, we modified a previously developed theory for two-phase two-component porous-medium flow, coupling it to single-phase two-component turbulent flow to simulate and analyze the evaporation from wavy soil surfaces. Detailed laboratory scale experiments using a wind tunnel interfaced with a porous media tank were carried out to test the modeling results. The characteristics of turbulent flow across a permeable wavy surface are discussed. Results demonstrate that there is an obvious recirculation zone formed at the surface, which is special because of the accumulation of water vapor and the thicker boundary layer in this area. In addition, the influences of both the free flow and porous medium on the evaporation are also analyzed. The porous medium affects the evaporation through the amount of water it can provide to the soil surface; while the atmosphere influences the evaporation

The use of biodegradable PLGA nanoparticles to mediate SOX9 gene delivery in human mesenchymal stem cells (hMSCs) and induce chondrogenesis.

PubMed

Kim, Jae-Hwan; Park, Ji Sun; Yang, Han Na; Woo, Dae Gyun; Jeon, Su Yeon; Do, Hyun-Jin; Lim, Hye-Young; Kim, Jung Mo; Park, Keun-Hong

2011-01-01

In stem cell therapy, transfection of specific genes into stem cells is an important technique to induce cell differentiation. To perform gene transfection in human mesenchymal stem cells (hMSCs), we designed and fabricated a non-viral vector system for specific stem cell differentiation. Several kinds of gene carriers were evaluated with regard to their transfection efficiency and their ability to enhance hMSCs differentiation. Of these delivery vehicles, biodegradable poly (DL-lactic-co-glycolic acid) (PLGA) nanoparticles yielded the best results, as they complexed with high levels of plasmid DNA (pDNA), allowed robust gene expression in hMSCs, and induced chondrogenesis. Polyplexing with polyethylenimine (PEI) enhanced the cellular uptake of SOX9 DNA complexed with PLGA nanoparticles both in vitro and in vivo. The expression of enhanced green fluorescent protein (EGFP) and SOX9 increased up to 75% in hMSCs transfected with PEI/SOX9 complexed PLGA nanoparticles 2 days after transfection. SOX9 gene expression was evaluated by RT-PCR, real time-qPCR, glycosaminoglycan (GAG)/DNA levels, immunoblotting, histology, and immunofluorescence. Copyright © 2010 Elsevier Ltd. All rights reserved.

Head-on collision of normal shock waves with rigid porous materials

NASA Astrophysics Data System (ADS)

Levy, A.; Ben-Dor, G.; Skews, B. W.; Sorek, S.

1993-08-01

The head-on collision of a planar shock wave with a rigid porous material has been investigated experimentally in a 75 mm × 75 mm shock tube. The experimental study indicated that unlike the reflection from a flexible porous material (e.g., polyurethane foam) where the transmitted compression waves do not converge to a sharp shock wave, in the case of a rigid porous material (e.g., alumina) the transmitted compression waves do converge to a sharp shock wave, which decays as it propagates along the porous material. In addition to this major difference, many other differences were observed. They are outlined in the following sections. Based on these observations a suggestion modifying the phenomenology of the reflection/interaction process in the case a porous material with large permeability is proposed.

Tortuosity correction of Kozeny's hydraulic diameter of a porous medium

NASA Astrophysics Data System (ADS)

Shin, C.

2017-02-01

The hydraulic diameter of a porous medium is the most important characteristic parameter governing porous flow aspects. Kozeny's hydraulic diameter has been used as the representative definition ever since he proposed it in 1927. However, it seems likely that this definition does not perfectly reflect the porous flow features even if the geometric relations of porous media are reasonably considered. Here we reviewed its definition by introducing Darcy's friction flow relation, and discovered that the term "tortuosity" should be included in the definition to more accurately characterize porous flows. Thus, the definition of "Tortuous Hydraulic Diameter (THD)," which corrects Kozeny's hydraulic diameter using tortuosity, is newly presented. Moreover, computational fluid dynamics simulations were performed to check the validity and applicability of the THD approach. As a result, it is seen that the THD demonstrates very low errors, with an average of 1.67%, whereas Kozeny's definition has relatively large errors, with an average of 12.8%. Accordingly, it is confirmed that the THD relation is the more accurate hydraulic diameter definition for a porous medium. Ultimately, the corrected definition can contribute to more reliable determinations of the other characteristic parameters and more reasonable porous flow analyses.

Ultrasonic Emission from Nanocrystalline Porous Silicon

NASA Astrophysics Data System (ADS)

Shinoda, Hiroyuki; Koshida, Nobuyoshi

A simple layer structure composed of a metal thin film and a porous silicon layer on a silicon substrate generates intense and wide-band airborne ultrasounds. The large-bandwidth and the fidelity of the sound reproduction are leveraged in applications varying from sound-based measurement to a scientific study of animal ecology. This chapter describes the basic principle of the ultrasound generation. The macroscopic properties of the low thermal conductivity and the small heat capacity of nanocrystalline porous silicon thermally induce ultrasonic emission. The state-of-the-art of the achievable sound pressure and sound signal properties is introduced, with the technological and scientific applications of the devices.

Variably porous structures

DOEpatents

Braun, Paul V [Savoy, IL; Yu, Xindi [Urbana, IL

2011-01-18

A method of making a monolithic porous structure, comprises electrodepositing a material on a template; removing the template from the material to form a monolithic porous structure comprising the material; and electropolishing the monolithic porous structure.

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.

Solutal Convection in Porous Media