Release of dexamethasone from PLGA nanoparticles entrapped into dextran/poly(vinyl alcohol) hydrogels

Hydrogels based on blends of poly(vinyl alcohol) (PVA) with dextran were prepared by a physical cross-linking procedure and used as matrices for the entrapment of biodegradable nanoparticles loaded with dexamethasone. The nanoparticles were prepared, by a solvent evaporation technique, using biodegradable copolymers of poly(lactic acid)–poly(glycolic acid) (PLGA). Size, morphology and surface characteristics of the nanoparticles were evaluated by scanning electron microscopy. The mechanism of drug release from the nanoparticles entrapped into the PVA-based matrices was studied and compared to that from free nanoparticles. The effect of dextran on the in vitro release profile of dexamethasone from the hydrogels was investigated. The obtained results indicate that PLGA nanoparticles are able to release dexamethasone following a diffusion-controlled mechanism. The entrapment of the nanoparticles into the hydrogels affects only slightly this mechanism of drug release. In addition, dextran/PVA hydrogels release a higher amount of drug with respect to pure PVA hydrogels and by increasing dextran content in the hydrogels, the amount of drug released increases.     

Poly(vinyl alcohol) hydrogels as hydrophilic matrices for the release of lipophilic drugs loaded in PLGA nanoparticles

Poly(vinyl alcohol) (PVA) hydrogels prepared by a freeze-thawing procedure were evaluated as matrices for the release of water-insoluble drugs such as dexamethasone. As it is impossible to directly entrap a lipophilic drug into a hydrophilic matrix, a novel mechanism has been designed based on producing biodegradable nanoparticles loaded with the drug, that could then be entrapped into the hydrogels. Nanoparticles were prepared by a solvent evaporation technique using a biodegradable copolymer of poly(lactic acid)-poly(glycolic acid) (PLGA). The effects of several processing parameters on particle properties were investigated. The drug release from free nanoparticles was compared to that from the nanoparticles entrapped into the PVA matrices. It was observed that the release profile of the drug is not significantly affected by the PVA matrix. A correlation was found between the amount of drug released and the PVA concentration in the hydrogels: the percentage of drug released, as a function of time, decreased by increasing PVA concentration, indicating that PVA concentration can be used as a tool in modulating the release of the drug.     

Nanoparticles with entrapped α-tocopherol: synthesis, characterization, and controlled release

An emulsion evaporation method was used to synthesize spherical poly(DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped α-tocopherol. Two different surfactants were used: sodium dodecyl sulfate (SDS) and poly(vinyl alcohol) (PVA). For SDS nanoparticles, the size of the nanoparticles decreased significantly with the entrapment of α-tocopherol in the PLGA matrix, while the size of PVA nanoparticles remained unchanged. The polydispersity index after synthesis was under 0.100 for PVA nanoparticles and around 0.150 for SDS nanoparticles. The zeta potential was negative for all PVA nanoparticles. The entrapment efficiency of α-tocopherol in the polymeric matrix was approximately 89% and 95% for nanoparticles with 8% and 16% α-tocopherol theoretical loading, respectively. The residual PVA associated with the nanoparticles after purification was approximately 6% ( w/w relative to the nanoparticles). The release profile showed an initial burst followed by a slower release of the α-tocopherol entrapped inside the PLGA matrix. The release for nanoparticles with 8% α-tocopherol theoretical loading (86% released in the first hour) was faster than the release for the nanoparticles with 16% α-tocopherol theoretical loading (34% released in the first hour).     

Manufacture,Characterization, and Release Profiles of Insulin-Loaded Mesoporous PLGA Microspheres

This paper reports the fabrication of insulin-loaded mesoporous microspheres by a double emulsion-solvent evaporation technique using poly(lactic acid-co-glycolic acid) (PLGA) as carrier materials. PLGA solutions with two different concentrations (4% and 5%) were used as the oil phases to fabricate the mesoporous microspheres. The morphology and the particle size distribution of final microspheres were studied by optical microscope, scanning electronic microscope (SEM), and Malvern 2600 sizer, respectively. The mesoporous microspheres were monodisperse with an average diameter of 7 ± 3.5 µm. Insulin, as a model drug, was encapsulated into the final microspheres. In vitro release studies suggested that insulin was continuously released from the medicated microspheres. Furthermore, the final microspheres obtained from 4% PLGA solution showed a small “burst release” effect for their dense structures, which shortened the lag time to the effective plasma concentration. To summarize, the insulin-loaded PLGA microsphere are very promising for use in pharmaceutical applications.     

Experimental design and multivariate analysis for optimizing poly(D,L-lactide-co-glycolide) (PLGA) nanoparticle synthesis using molecular micelles

The utility of polymeric nanoparticles as drug delivery systems depends on effective control of synthetic parameters with a significant impact on their physico-chemical characteristics. In this study, a chemometric central composite experimental design (CCD) was used to optimize the synthesis of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles by emulsification solvent evaporation using anionic molecular micelles, such as poly(sodium N-undecylenic sulfate) (poly-SUS), poly(sodium N-undecanoyl-glycinate) (poly-SUG) and poly(sodium N-undecanoyl-L-leucyl-valinate) (poly-L-SULV) as well as conventional emulsifiers, such as anionic sodium dodecyl sulfate (SDS) and non-ionic poly(vinyl alcohol) (PVA). The individual and combined effects of PLGA concentration, emulsifier concentration, homogenization speed, and sonication time (design variables) on particle size and polydispersity index (responses) were investigated using multivariate analysis. The most significant design variables influencing the nanoparticle size and size distribution were PLGA concentration and emulsifier concentration (p < 0.05) in comparison to the other design variables. The quadratic model demonstrated the highest predictive ability when the molecular micelles were used as emulsifiers. The PLGA nanoparticles optimally synthesized according to the CCD were further purified by dialysis and then freeze-dried. Dried nanoparticles synthesized with molecular micelles and PVA were readily re-suspended in water, as compared with SDS for which nanoparticle aggregation occurred. The size of PLGA nanoparticles synthesized using molecular micelles increased after freeze-drying, but remained smaller than 100 nm when poly-L-SULV was used as emulsifier. The PDI values indicated monodisperse nanoparticle suspensions after purification and freeze-drying for all investigated molecular micelles (PDI < 0.100). The nanoparticle suspensions synthesized using molecular micelles were the most stable after dialysis and freeze-drying, having low negative zeta potential values ranging from -54 +/- 1.6 mV for poly-L-SULV to -63.2 +/- 0.4 mV for poly-SUS. Transmission electron microscopy (TEM) micrographs showed spherical shape and smooth surface for the PLGA nanoparticles synthesized using molecular micelles.     

Optimization of PLGA nanoparticles formulation containing L-DOPA by applying the central composite design

The aim of this work was to prepare L-DOPA loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles by a modified water-in-oil-in-water (W₁/O/W₂) emulsification solvent evaporation method. A central composite design was applied for optimization of the formulation parameters and for studying the effects of three independent variables: PLGA concentration, polyvinyl alcohol (PVA) concentration and organic solvent removal rate on the particle size and the entrapment efficiency (response variables). Second-order models were obtained to adequately describe the influence of the independent variables on the selected responses. The analysis of variance showed that the three independent variables had significant effects (p < 0.05) on the responses. The experimental results were in perfect accordance with the predictions estimated by the models. Using the desirability approach and overlay contour plots, the optimal preparation area can be highlighted. It was found that the optimum values of the responses could be obtained at higher concentration of PLGA (5%, w/v) and PVA (6%, w/v); and faster organic solvent removal rate (700 rpm). The corresponding particle size was 256.2 nm and the entrapment efficiency was 62.19%. FTIR investigation confirmed that the L-DOPA and PLGA polymer maintained its backbone structure in the fabrication of nanoparticles. The scanning electron microscopic images of nanoparticles showed that all particles had spherical shape with porous outer skin. The results suggested that PLGA nanoparticles might represent a promising formulation for brain delivery of L-DOPA. The preparation of L-DOPA loaded PLGA nanoparticles can be optimized by the central composite design.     

Effects of poly (lactic-co-glycolic acid) as a co-emulsifier on the preparation and hypoglycaemic activity of insulin-loaded solid lipid nanoparticles

Poly (lactic-co-glycolic acid) (PLGA) was used as a co-emulsifier in the preparation of insulin-loaded solid lipid nanoparticles (SLN) with hydrogenated castor oil as lipid matrix and lecithin as surfactant by doubleemulsion technique. The effects of PLGA on the preparation and hypoglycaemic activity of insulin-loaded SLN were studied. The results showed that with the supplement of PLGA, the encapsulation efficiency and loading capacity were increased significantly from 79.08±1.62 to 85.57±3.21% and 1.58±0.03 to 1.71±0.06%, whereas the surface charge and particle size were changed insignificantly from -25.87±2.65 to -22.67±1.19 mv and 431.0±16.1 to 397.0±68.0 nm, respectively. In vivo studies demonstrated that PLGA increased the sustained hypoglycaemic activity from 12 to 36 h and 24 to 120 h in normal and steptozotocin-induced diabetic mice after a single intramuscular injection of the insulin-loaded SLN. These results demonstrated that PLGA could enhance the entrapment of insulin in the nanoparticles, and more importantly, prolong the time of hypoglycaemic activity of the insulin-loaded SLN.     

Preparation and Optimization of Dry PLGA Nanoparticles by Spray Drying Technique

The aim of this article was to evaluate the potential of poly lactide-coglycolide (PLGA) nanoparticles (NPs) as carriers for controlling release of doxorubicin (DOX) via a spray drying technique. The challenge was to entrap a hydrophilic molecule into a lipophilic core molecule of PLGA. To achieve this objective, we modified conventional approach of drug loading to spray drying technique. The eight formulations of nanoparticles were prepared by modified double emulsion and solvent evaporation technique followed by spray drying using 2³ factorial designs. PLGA (A) and PVA (B) and stirring speed (C) were used as independent variables where particle size (Y₁), entrapment efficiency (Y₂) and percentage of drug release at the 32 hour (Y₃) were taken as dependant variables. The results showed that the method is easy and efficient for the entrapment of the drug as well as the formation of spherical nanoparticles. This modification improved DOX entrapment efficiency relative to controls real loadings up to 40%. The in vitro release studies indicated the DOX loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of DOX-PLGA nanoparticles.     

Preparation and evaluation of paclitaxel-loaded nanoparticle incorporated with galactose-carrying polymer for hepatocyte targeted delivery

Objective: Paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles incorporated with galactose-carrying polymer poly(vinyl benzyllactonamide) (PVLA) were prepared to facilitate the hepatocyte cell targeted delivery of paclitaxel via ligand-receptor mediated endocytosis. The factors impacting nanoparticle properties, drug release and cellular uptake efficiency were evaluated in vitro.

Method: Paclitaxel-loaded nanoparticles incorporated with PVLA were prepared by emulsion solvent evaporation method with polyvinyl alcohol (PVA) as co-emulsifier. The presence of PVLA on the particle surface was investigated through the change of ζ potential and surface hydrophobicity. Cellular uptake and cytotoxic activity, involving factors concerned with them, were evaluated by HepG2 cells in vitro.

Results: The presence of PVLA led to the increase of ζ potential, reduction of the particle surface hydrophobicity, slight promotion of paclitaxel encapsulation efficiency and more homogeneous particle size, but excessive PVLA accelerated the burst release. With enhanced attachment and cellular uptake efficiency, the PVLA incorporated nanoparticles exhibited significant cytotoxicity to HepG2 cells, and particles with higher PVLA-to-PLGA ratio, although had larger size and almost the same cellular uptake efficiency, performed much higher cytotoxic activity due to the larger drug capacity and faster release rate.     

Microspheres for the oral delivery of insulin: preparation,evaluation and hypoglycaemic effect in streptozotocin-induced diabetic rats

Insulin-loaded microspheres were prepared by alternating deposition film layers that were composed of insulin and poly(vinyl sulfate) potassium on the surface of poly(lactic acid) (PLA) microspheres. The preparation of the insulin-loaded microspheres was optimized by an orthogonal test design, and the relationship between drug loading (DL) and film layers was studied. The particle size, DL and encapsulation efficiency of the obtained insulin-loaded microspheres with 10 films were 5.25?±?0.15?µm, 111.33?±?1.15?mg/g and 33.7?±?0.19%, respectively. Following this, the physical characteristics of the insulin-loaded microspheres were investigated. The results from scanning electron microscopy and a laser particle size analyzer (LPSA) indicated the spherical morphology, rough surface and increasing particle sizes of the insulin-loaded microspheres, which were compared to those of PLA microspheres. An in vitro release study showed that the insulin-loaded microspheres were stable in HCl solution (pH 1.0) and released insulin slowly in phosphate-buffered solution (pH 6.8). Finally, the drug efficacy of the prepared insulin-loaded microspheres via oral administration was evaluated in rats with diabetes induced by streptozotocin, and an obvious dose-dependent hypoglycemic effect was observed. This preliminary data could illustrate the prospect of using microspheres for the oral delivery of insulin.     

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

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

Development and in vitro evaluation of surface modified poly(lactide-co-glycolide) nanoparticles with chitosan-4-thiobutylamidine

The objective of this study was to develop a nanoparticulate drug delivery system based on the surface modification of poly(lactide-co-glycolide) (PLGA) nanoparticles with a thiolated chitosan. PLGA nanoparticles were prepared by the emulsification-solvent evaporation method. Immobilization of chitosan to the surface of PLGA nanoparticles via amide bonds was mediated by a carbodiimide. Thiol groups were covalently bound to the chitosan surface of particles by reaction with 2-iminothiolane. Obtained nanoparticles were characterized in vitro regarding size, zeta potential, thiol group content, stability at different pH values, mucoadhesion, and drug release. Results demonstrated that the surface modification of PLGA nanoparticles with thiolated chitosan (chitosan-TBA) leads to nanoparticles of a mean diameter of 889.5 ± 72 nm and positive zeta potential of + 24.74 mV. The modified nanoparticles contained 7.32 ± 0.24 μmol thiol groups per gram nanoparticles. The size of nanoparticles was strongly influenced by the pH of the surrounding medium, being 925.0 ± 76.3 nm at pH 2 and 577.8 ± 66.7 nm at pH 7.4. Thiolated nanoparticles showed a 3.3-fold prolonged residence time on the mucosa and an unchanged release profile in comparison to unmodified PLGA nanoparticles. These data suggest that surface modified chitosan-TBA conjugate PLGA nanoparticles have the potential to be used as mucoadhesive drug delivery system.     

Preparation and in vitro evaluation of meloxicam-loaded PLGA nanoparticles on HT-29 human colon adenocarcinoma cells

Context: The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certain COX-2 inhibitors exert antiproliferative and pro-apoptotic effects on cancer cells.

Objective: In this study, meloxicam, which is an enolic acid-type preferential COX-2 inhibitor, was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to maintain local high concentration, and its efficacy was determined.

Methods: NPs were prepared by using salting-out and emulsion-evaporation steps. Meloxicam-loaded NP formulations were evaluated with respect to the drug loading, particle size, polydispersity index, zeta potential, drug release rate, and residual poly(vinyl alcohol) (PVA) percentage. The effects of PLGA and PVA molecular weight variations on the physicochemical properties of NPs were investigated. Stability of meloxicam in NPs was assessed over 3 months. COX-2 expressing human colon adenocarcinoma cell line HT-29 was used in cellular uptake and viability assays.

Results: NPs had a spherical shape and a negative zeta potential, and their size ranged between 170–231?nm with a lower polydispersity index. NPs prepared with high molecular weight PLGA were shown to be physically stable over three months at 4°C. The increase in molecular weight of the polymer and emulsifier reduced the in vitro release rate of meloxicam from NPs. Meloxicam-loaded NPs showed cytotoxic effects on HT-29 cells markedly at 800 µM. Cancer cells had high uptake of coumarin-6-loaded NPs.

Conclusion: The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.     

Development and In Vitro Evaluation of Surface Modified Poly(lactide-co-glycolide) Nanoparticles with Chitosan-4-Thiobutylamidine

ABSTRACT

The objective of this study was to develop a nanoparticulate drug delivery system based on the surface modification of poly(lactide-co-glycolide) (PLGA) nanoparticles with a thiolated chitosan. PLGA nanoparticles were prepared by the emulsification-solvent evaporation method. Immobilization of chitosan to the surface of PLGA nanoparticles via amide bonds was mediated by a carbodiimide. Thiol groups were covalently bound to the chitosan surface of particles by reaction with 2-iminothiolane. Obtained nanoparticles were characterized in vitro regarding size, zeta potential, thiol group content, stability at different pH values, mucoadhesion, and drug release. Results demonstrated that the surface modification of PLGA nanoparticles with thiolated chitosan (chitosan-TBA) leads to nanoparticles of a mean diameter of 889.5 ± 72 nm and positive zeta potential of + 24.74 mV. The modified nanoparticles contained 7.32 ± 0.24 μmol thiol groups per gram nanoparticles. The size of nanoparticles was strongly influenced by the pH of the surrounding medium, being 925.0 ± 76.3 nm at pH 2 and 577.8 ± 66.7 nm at pH 7.4. Thiolated nanoparticles showed a 3.3-fold prolonged residence time on the mucosa and an unchanged release profile in comparison to unmodified PLGA nanoparticles. These data suggest that surface modified chitosan-TBA conjugate PLGA nanoparticles have the potential to be used as mucoadhesive drug delivery system.     

Modified nanoprecipitation method to fabricate DNA-loaded PLGA nanoparticles

Objective: The objective of this study was to formulate DNA-loaded poly(d,l-lactide-co-glycotide) (PLGA) nanoparticles by a modified nanoprecipitation method. Methods: DNA-loaded PLGA nanoparticles were prepared by the modified nanoprecipitation method and the double emulsion/solvent evaporation method. The characterizations of DNA-loaded nanoparticles such as entrapment efficiency, morphology, particle size, zeta potential, structural integrity of the loaded DNA, and stability of the loaded DNA in PLGA nanoparticles against DNase I, in vitro release, cell viability and in vitro transfection capability were investigated. Results: The resulted PLGA nanoparticles by the modified nanoprecipitation method had uniform spherical shape, narrow size distribution with average particles size near 200 nm, negative zeta potential of ?12.6 mV at pH 7.4, and a sustained-release property in vitro. Plasmid DNA could be efficiently encapsulated into PLGA nanoparticles (>95%) without affecting its intact conformation using this modified nanoprecipitation method, which was superior to the double emulsion/solvent evaporation method. The PLGA nanoparticles were much safer to A549 cell compared to commercial Lipofectamine 2000 and could successfully transfer plasmid-enhanced green fluorescent protein into A549 cells. Conclusion: In conclusion, the modified nanoprecipitation method could be applied as an efficient way to fabricate DNA-loaded PLGA nanoparticles instead of the conventional double emulsion/solvent evaporation method.     

Impact of surfactant selection on the formulation and characterization of microparticles for pulmonary drug delivery

The effect of suspension stabilizers, internal aqueous phase volume and polymer amount were investigated for the production of protein loaded poly(d,l?lactide-co-glycolide) (PLGA) microparticles suitable for pulmonary drug delivery. PLGA microparticles were produced adopting water-in-oil-in-water (W/O/W) solvent evaporation technique and were investigated for surface morphology, particle size, encapsulation efficiency (EE%) and in-vitro release profile. Porous surface morphologies with a narrow size distribution were observed when employing 0.5?ml internal aqueous phase; 23.04?µm (±0.98), 15.05?µm (±0.27) and 22.89?µm (±0.41) for PVA, Tween 80 and oleic acid. Porous microparticles exhibited increased size and reduction in EE% with increasing internal aqueous phase, with non-porous microparticles produced when adopting 2.0?ml internal aqueous phase. The selection of stabilizer influences the size of the pores formed thus offers potential for the aerodynamic properties of the microparticles to be manipulated to achieve suitable aerosolization characteristics for pulmonary delivery of proteins.     

Fabrication and characterization of porous poly(lactic-<Emphasis Type="Italic">co</Emphasis>-glycolic acid) (PLGA) microspheres for use as a drug delivery system

In this work, Simvastatin (SIM) loaded porous poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated using the W/O/W1/W2 double emulsion and solvent evaporation method. The optimal conditions for fabricating porous PLGA microspheres were determined to be 20% distilled water (v/v), 10% PLGA (m/v), and a 4:1 ratio of internal polyvinyl alcohol (PVA) to dichloromethane (DCM). The pores size distribution of porous PLGA microspheres was varied from 0.01 to 40 μm, while their particle displayed a bimodal size distribution that had two diameter peaks at around 100 μm and 500 μm. The SIM encapsulation efficacy was found to be very high with a yield near 80% and the porous PLGA microspheres showed the excellent biocompatibility. In addition, the drug release profile was found to be significantly different from a temporal basis. Base on the combined results of this study, SIM loaded PLGA microspheres holds great promise for use in biomedical applications, especially in drug delivery system or tissue regeneration.     

Nanocarriers with gentamicin to treat intracellular pathogens

Brucellosis is a worldwide zoonosis caused by different species of the genus Brucella. The intracellular localisation of this pathogen, particularly in macrophages, renders treatment difficult since most antibiotics known to be efficient in vitro do not actively pass through cellular membranes. As alternative to current treatment, polymeric drug delivery systems containing gentamicin have been developed. These particulate carriers target the drug into the mononuclear-phagocytic system, where the pathogen resides that will allow intracellular accumulation of the antibiotic after particle degradation. Besides, particle uptake may induce macrophage activation, increasing the production of reactive oxygen intermediates, involved in host defense against the intracellular pathogen. The aim of the present work was to study the suitability of polymeric nanoparticles for gentamicin entrapment in view to treat brucellosis. Different poly(lactide-co-glycolide) PLGA polymers were used to formulate the nanoparticles containing gentamicin by a water-oil-water solvent evaporation method. Furthermore, in vitro macrophage activation upon nanoparticles phagocytosis and in vivo distribution of the nanocarriers in the target organs for Brucella (liver and spleen) were also studied. The nanoparticle sizes were below 350 nm, the gentamicin encapsulation efficiency depended on the polymer type used for their preparation and the in vitro release of the antibiotic exhibited a continuos pattern (PLGA 502H). PLGA 502H nanoparticles were the most suitable due to the highest entrapment and the most sustained release. The nanoparticles were successfully phagocyted by a J774 murine monocytes cell line and biodistribution studies in mice after intravenous administration of the delivery systems revealed that the particles reached the target organs of Brucella (liver and spleen). All together, these results indicate that the nanocarriers described in this work may be suitable as gentamicin delivery system to control brucellosis.     

Targeted biodegradable nanoparticles for drug delivery to smooth muscle cells

Targeted delivery of therapeutic agents to prevent smooth muscle cell (SMC) proliferation is important in averting restenosis (a narrowing of blood vessels). Since platelet derived growth factor (PDGF) receptors are over-expressed in proliferating SMCs after injury from cardiovascular interventions, such as angioplasty and stent implantation, our hypothesis is that conjugation of PDGF-BB (platelet-derived growth factor BB (homodimer)) peptides to biodegradable poly (D,L-lactic-co-glycolide) (PLGA) nanoparticles (NPs) would exhibit an increased uptake of these NPs by proliferating SMCs. In this study, poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles containing dexamethasone were formulated and conjugated with PDGF-BB peptides. These NPs were stable, biocompatible, and exhibited a sustained drug release over 14 days. Various particle uptake studies using HASMCs (human aortic smooth muscle cells) demonstrated that PDGF-BB peptide-conjugated nanoparticles significantly increased cellular uptake and decreased proliferation of HASMCs compared to control nanoparticles (without conjugation of PDGF-BB peptides). These NPs were internalized primarily by clathrin-mediated endocytosis and macropinocytosis. Our in vitro results suggest that PDGF-BB peptide-conjugated NPs could represent as an effective targeted, sustained therapeutic delivery system to reduce restenosis and neointimal hyperplasia.     

Ultrafine PEG-coated poly(lactic-co-glycolic acid) nanoparticles formulated by hydrophobic surfactant-assisted one-pot synthesis for biomedical applications

A novel method was developed for the one-pot synthesis of ultrafine poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), using an emulsion solvent evaporation formulation method. Using either cetyltrimethylammonium bromide (CTAB) or poly(ethylene glycol)-distearyl phosphoethanolamine (PEGPE) as an oily emulsifier during the emulsion process, produced PLGA particle sizes of less than 50 nm, constituting a breakthrough in emulsion formulation methods. The yield of ultrafine PLGA NPs increased with PEGPE/PLGA ratio, reaching a plateau at around 85%, when the PEGPE/PLGA ratio reached 3:1. The PEGPE-PLGA NPs exhibited high drug loading content, reduced burst release, good serum stability, and enhanced cell uptake rate compared with traditional PLGA NPs. Sub-50 nm diameter PEG-coated ultrafine PLGA NPs show great potential for in vivo drug delivery systems.