Synthesis, characterization, and in vitro 5-Fu release behavior of poly(2,2-dimethyltrimethylene carbonate)-poly(ethylene glycol)-poly(2,2-dimethyltrimethylene carbonate) nanoparticles

Novel ABA-type amphiphilic triblock copolymers composed of poly (ethylene glycol) (PEG) as hydrophilic segment and poly (2,2-dimethyltrimethylene carbonate) (PDTC) as hydrophobic segment were synthesized by ring-opening polymerization of 2,2-dimethyltrimethylene carbonate (DTC) initiated by dihydroxyl PEG. The influence of introducing PEG block on crystalline behavior of PDTC segment was investigated by DSC. Polymeric micelles in aqueous medium were characterized by fluorescence spectroscopy and dynamic light scattering. The critical micelle concentration of these copolymers was in the range of 5.1-50.5 mg/L. Particle size was 80-280 nm. Core-shell-type nanoparticles were prepared by the dialysis technique. Zeta potential was measured by laser Doppler anemometry, and all nanoparticles had negative zeta potential. Transmission electron microscopy images demonstrated that these nanoparticles were spherical in shape. Anticancer drug 5-fluorouracil (5-Fu) as a model drug was loaded in the polymeric nanoparticles. X-ray powder diffraction demonstrated that 5-Fu was encapsulated into polymeric nanoparticles as molecular dispersion. In vitro cytotoxicity of nanoparticles was evaluated by MTT assay. In vitro release behavior of 5-Fu was investigated, and sustained drug release was achieved.     

Oligo(trimethylene carbonate)-poly(ethylene glycol)-oligo(trimethylene carbonate) triblock-based hydrogels for cartilage tissue engineering

A triblock co-polymer of oligo(trimethylene carbonate)-block-poly(ethylene glycol) 20000-block-oligo(trimethylene carbonate) diacrylate (TMC20) was used as a photo-polymerizable precursor for the encapsulation of primary articular chondrocytes. The efficacy of TMC20 as a biodegradable scaffold for cartilage tissue engineering was compared with non-degradable poly(ethylene glycol) 20000 diacrylate (PEG20) hydrogel. Chondrocytes encapsulated in PEG hydrogels containing oligo(trimethylene carbonate) (OTMC) moieties underwent spontaneous aggregation during in vitro culture, which was not observed in the PEG hydrogel counterparts. The aggregation of cells was found to be dependent on the initial cell density, as well as the mesh size of the hydrogels. Similarly, cell aggregation was also found in biodegradable PEG hydrogels containing caprolactone moieties. The aggregation of cells in TMC20 hydrogels resulted in enhanced cartilage matrix production compared with their PEG20 counterparts over 3 weeks of culture. Taken together, these results indicate that PEG hydrogels containing degradable OTMC moieties promote the aggregation and biosynthetic activity of encapsulated chondrocytes, indicating their potential as scaffolds for the repair of cartilage tissue.     

Synthesis and in vitro drug release behavior of amphiphilic triblock copolymer nanoparticles based on poly (ethylene glycol) and polycaprolactone

Novel BAB type amphiphilic triblock copolymers consisting of poly (ethylene glycol) (PEG) (B) as hydrophilic segment and poly (epsilon-caprolactone) (PCL) (A) as hydrophobic block were prepared by coupling reaction using L-lysine methyl ester diisocyanate (LDI) as the chain extender. The triblock copolymers obtained were characterized by FT-IR, 1H NMR, GPC, and DSC. Core-shell type nanoparticles were prepared by nanoprecipitation method and below 100 nm nanoparticles were obtained due to their specific structure. Transmission electron microscopy image demonstrated that these nanoparticles were spherical in shape. Stability of the nanoparticles in biological media was evaluated. Poorly water-soluble anticancer drug 4'-demethyl-epipodophyllotoxin (DMEP) was chosen for controlled drug release because it was easily encapsulated into polymeric nanoparticles via hydrophobic interaction. In vitro release behavior of DMEP from polymeric nanoparticles was investigated, the results showed that the drug release rate can be modulated by the variation of the copolymer composition.     

Biodegradable and thermoreversible hydrogels of poly(ethylene glycol)-poly(epsilon-caprolactone-co-glycolide)-poly(ethylene glycol) aqueous solutions

The aqueous solutions of triblock copolymers of poly(ethylene glycol)-poly(epsilon-caprolactone-co-glycolide)-poly(ethylene glycol) [PEG-P(CL-GA)-PEG] undergoing sol-gel transition as the temperature increases from 20 to 60 degrees C were successfully prepared. The thermogelling block copolymers were synthesized by subtle control of the hydrophilic/hydrophobic balance and the chain microstructures. The amphiphilic block copolymer formed micelles in aqueous solution, and the micelle aggregated as the temperature increased. The sol-gel transition of the copolymer aqueous solutions was studied focusing on the structure-property relationship. GA was incorporated into the polymer chain to prevent crystallization of PCL component and increase the polymer degradation. It is expected to be a promising long-term delivery system for pH-sensitive drugs, proteins, and genes.     

对映异构聚乳酸/聚乙二醇空间异构复合水凝胶的药物释放及形貌和细胞毒性

背景：目前生物降解水凝胶已被广泛应用于抗癌药物及生物活性大分子的装载,但为了保护生物活性大分子的活性,需要得到凝胶化条件更温和,凝胶化时间更短的凝胶体系。 目的：制备对映异构聚乳酸∕聚乙二醇的空间异构复合水凝胶,使其具有更短的凝胶化时间,实现对模拟药物溶菌酶的装载和控释。 方法：以聚乙二醇为引发剂,辛酸亚锡为催化剂,丙交酯与聚乙二醇发生开环聚合反应,得到聚乳酸/聚乙二醇的三嵌段共聚物(PLLA-PEG-PLLA 和 PDLA-PEG-PDLA)。用1H NMR,FT-IR 和 XRD表征三嵌段共聚物。10% PLLA20-PEG227-PLLA20的水溶液和10%PDLA21-PEG227-PDLA21的水溶液在室温下混合,12 h后形成凝胶。通过XRD考察凝胶化机制,以溶菌酶为模拟药物,考察凝胶的释药特性,通过扫描电镜考察凝胶的形貌,采用MTT法考察凝胶的细胞毒性。 结果与结论：成功得到聚乳酸/聚乙二醇的三嵌段共聚物,在嵌段共聚物中,聚乳酸嵌段和聚乙二醇嵌段都能结晶,但以聚乙二醇嵌段的结晶为主。通过XRD证明凝胶中存在空间异构复合作用,溶菌酶在凝胶中通过凝胶的溶蚀和降解行为,在7 d之内释放完全。通过扫描电镜观察到冻干的水凝胶呈三维贯穿的多孔结构,空隙尺寸在50~100 μm 之间。鼠成纤维细胞与浓度为100%的凝胶浸提液共培养72 h之后,细胞的存活率为99.3%。     

One-step preparation of poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) nanoparticles for plasmid DNA delivery

In this article, a kind of biodegradable poly(epsilon-caprolactone)-Poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) copolymer was synthesized by ring-opening polymerization method. The PCEC nanoparticles were prepared at one-step by modified emulsion solvent evaporation method using CTAB as stabilizer. With increase in PCEC concentration, the particle size increased obviously, but zeta potential only increased slightly. The obtained cationic PCEC nanoparticle was employed to condense and adsorb DNA onto its surface. Plasmid GFP (pGFP) was used as model plasmid to evaluate the loading capacity of cationic PCEC nanoparticles in this work. The DNA/nanoparticles weight ratio at 1:16 induced almost neutral zeta potential of DNA-nanoparticles complex. At this time, the size of complex became abnormally large which implied aggregates formed. So DNA-nanoparticles weight ratio should be chosen carefully. The cationic PCEC nanoparticles had the capacity of condensing plasmid DNA into complex when the DNA/nanoparticles weight ratio was lower than 1:8, which was evidenced by gel retardation assay. In vitro release behavior of DNA/nanoparticle complexes was also studied here. The obtained cationic PCEC nanoparticles might have great potential application in DNA delivery.     

Preparation and drug release behaviors of nimodipine-loaded poly(caprolactone)-poly(ethylene oxide)-polylactide amphiphilic copolymer nanoparticles

Amphiphilic block copolymers, poly(caprolactone)-poly(ethylene glycol)-poly(lactide) (PCELA), were synthesized by ring opening polymerization of caprolactone and lactide initiated with the hydroxyl groups of poly(ethylene glycol) (PEG). These copolymers could form micelle-like nanoparticles due to their amphiphilic characteristic. From the observation of transmission electron microscopy (TEM), the nanoparticles exhibited a regular spherical shape with core-shell structure. The critical micelle concentrations (CMC) of these nanoparticles in water were decreased as molecular weight of PEG decreased. The particle sizes obtained by dynamic light scattering of these nanoparticles were in the range of 100-200 nm, and increased as the hydrophobic property of the nanoparticles increased. Nimodipine as a model drug was loaded in these nanoparticles to investigate the drug release behavior. It was found that the chemical composition of the nanoparticles was a key factor in controlling nanoparticle size, nanoparticle yields, drug-entrapment efficiency, and drug release behavior. When the PEG content is about 2% (wt), the release profile of PCELA nanoparticles appeared to follow zero-order kinetics.     

In vitro cytotoxicity, hemolysis assay, and biodegradation behavior of biodegradable poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) nanoparticles as potential drug carriers

Nanoparticles based on amorphous poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) (PHB-PEG-PHB) are potential drug delivery vehicles, and so their cytotoxicity and hemolysis assay were investigated in vitro using two kinds of animal cells. The PHB-PEG-PHB nanoparticles showed excellent biocompatibility and had no cytotoxicity on animal cells, even when the concentrations of the PHB-PEG-PHB nanoparticle dispersions were increased to 120 microg/mL. Moreover, no hemolysis was detected with the PHB-PEG-PHB nanoparticles, suggesting that the PHB-PEG-PHB nanoparticles were obviously much hemocompatible for drug delivery applications. In the presence of intracellular enzyme esterase, the biocompatible PHB-PEG-PHB nanoparticles might be hydrolyzed, and their biodegradable behavior was monitored by the fluorescence spectrum and the pH meter. The initial biodegradation rate of the PHB-PEG-PHB nanoparticles was closely related to the enzymatic amount and the PHB block length. Compared with that obtained from the fluorescence determination, the initial biodegradation rate from pH measurement was faster. The biodegraded products mainly consisted of 3HB monomer and dimer, which were the metabolites present in the body.     

Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs

Methoxy poly(ethylene glycol)-poly(lactide) copolymer (MPEG-PLA) was synthesized and used to make nanoparticles by the nanoprecipitation method for clinical administration of antineoplastic drugs. Paclitaxel was used as a prototype drug due to its excellent efficacy and commercially great success. The size and size distribution, surface morphology, surface charge and surface chemistry of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, atomic force microscopy, zeta-potential analyzer and X-ray photoelectron spectroscopy (XPS). The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography. The effects of various formulation parameters were evaluated. The prepared nanoparticles were found of spherical shape with size less than 100 nm. Zeta potential measurement and XPS analysis demonstrated the presence of PEG layer on the particle surface. Viscosity of the organic phase was found to be one of the main process factors for the size determination. The EE was found to be greatly influenced by the drug loading. The drug release pattern was biphasic with a fast release rate followed by a slow one. The particle suspension exhibited good steric stability in vitro. Such a nanoparticle formulation of paclitaxel can be expected to have long-circulating effects in circulation.     

Synthesis, characterization and drug release from three-arm poly(epsilon-caprolactone) maleic acid/poly(ethylene glycol) diacrylate hydrogels

A biodegradable polymer network hydrogel with both hydrophobic and hydrophilic components was synthesized and characterized. The hydrophobic and hydrophilic components were a three-arm poly(epsilon-caprolactone) maleic acid (PGCL-Ma, as the hydrophobic constituent) and poly(ethylene glycol) diacrylate macromer (PEGDA, as a hydrophilic constituent), respectively. These two polymers were chemically photo-crosslinked to generate a three-dimensional network structure, which were characterized by FT-IR, DSC and SEM. The swelling property of the networks was studied in phosphate-buffered saline (PBS, pH 7.4). The results of this study showed that a wide-range swelling property was obtained by changing the composition ratio of PGCL-Ma to PEGDA. The in vitro release of bovine serum albumin (BSA) from these hydrogels as a function of the PEGDA to PGCL-Ma composition ratio and incubation time was examined and we found that the incorporation of PEGDA into PGCL-Ma increased the initial burst release of BSA. As the PEGDA component increased, the rate of formation of a loose three-dimensional (3D) network structure increased; consequently, the sustained rate and extent of BSA release increased. We suggest that the release of BSA was controlled by both diffusion of BSA through swelling of the hydrophilic phase during an early stage and degradation of the hydrophobic phase during a late stage; and that the relative magnitude of diffusion versus degradation controlled release depended on composition ratio and immersion time.     

Osteogenic potential of poly(ethylene glycol)-poly(dimethylsiloxane) hybrid hydrogels

Growth factors have been shown to be potent mediators of osteogenesis. However, their use in tissue-engineered scaffolds not only can be costly but also can induce undesired responses in surrounding tissues. Thus, the ability to specifically induce osteogenic differentiation in the absence of exogenous growth factors through manipulation of scaffold material properties would be desirable for bone regeneration. Previous research indicates that addition of inorganic or hydrophobic components to organic, hydrophilic scaffolds can enhance multipotent stem cell (MSC) osteogenesis. However, the combined impact of scaffold inorganic content and hydrophobicity on MSC behavior has not been systematically explored, particularly in three-dimensional (3D) culture systems. The aim of the present study was therefore to examine the effects of simultaneous increases in scaffold hydrophobicity and inorganic content on MSC osteogenic fate decisions in a 3D culture environment toward the development of intrinsically osteoinductive scaffolds. Mouse 10T? MSCs were encapsulated in a series of novel scaffolds composed of varying levels of hydrophobic, inorganic poly(dimethylsiloxane) (PDMS) and hydrophilic, organic poly(ethylene glycol) (PEG). After 21 days of culture, increased levels of osteoblast markers, runx2 and osteocalcin, were observed in scaffolds with increased PDMS content. Bone extracellular matrix (ECM) molecules, collagen I and calcium phosphate, were also elevated in formulations with higher PDMS:PEG ratios. Importantly, this osteogenic response appeared to be specific in that markers for chondrocytic, smooth muscle cell, and adipocytic lineages were not similarly affected by variations in scaffold PDMS content. As anticipated, the increase in scaffold hydrophobicity accompanying increasing PDMS levels was associated with elevated scaffold serum protein adsorption. Thus, scaffold inorganic content combined with alterations in adsorbed serum proteins may underlie the observed cell behavior.     

Preparation and characterization of poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) microspheres for controlled release of paclitaxel

Microspheres of a new kind of copolymer, poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA), are proposed in the present work for clinical administration of an antineoplastic drug paclitaxel with hypothesis that incorporation of a hydrophilic PEG segment within the hydrophobic PLA might facilitate the paclitaxel release. Paclitaxel-loaded PLA-PEG-PLA microspheres of various compositions were prepared by the solvent extraction/evaporation method. Characterization of the microspheres was then followed to examine the particle size and size distribution, the drug encapsulation efficiency, the colloidal stability, the surface chemistry, the surface and internal morphology, the drug physical state and its in vitro release behavior. The effects of polymer types, solvents and drug loading were investigated. It was found that in the microspheres the PEG segment was homogeneously distributed and caused porosity. Significantly faster release from PLA-PEG-PLA microspheres resulted in comparison with the PLGA counterpart. Incorporation of water-soluble solvent acetone in the organic solvent phase further increased the porosity of the PLA-PEG-PLA microspheres and facilitated the drug release. A total of 49.6% sustained release of paclitaxel within 1 month was achieved. Potentially, the presence of PEG on the surface of PLA-PEG-PLA microspheres could improve their biocompatibility. PLA-PEG-PLA microspheres could thus be promising for the clinical administration of highly hydrophobic antineoplastic drugs such as paclitaxel.     

Effects of ethylene oxide gas sterilization on physical properties of poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) microspheres

The aggregation of poly(alpha-hydroxy acid) microspheres during ethylene oxide (EO) gas sterilization makes it difficult for the microspheres to be used in clinical applications. In this study, six kinds of PLLA-PEG-PLLA triblock copolymers (TriPLE) were synthesized with various composition ratios of PEG/PLLA in the range of 0.012 to 0.103. TriPLE microspheres were prepared by the oil-in-water emulsion method. TriPLE microspheres were characterized by using 1H-NMR, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). After sterilization by EO gas at 55 degrees C, the microspheres were analyzed by scanning electron microscope (SEM), laser diffractometry, standard sieves, X-ray diffraction (XRD), GPC, and DSC. When the composition ratio of PEG/PLLA was above 0.02, the initial crystallinity of TriPLE in microspheres was as high as 50%, and the microspheres were suitable to be sterilized by EO gas. On the other hand, TriPLE microspheres, which had composition ratios of PEG/PLLA below 0.02, had low initial crystallinities of about 30%, and aggregated during EO gas sterilization. For these microspheres, crystallinity increased up to 50% during the sterilization, whereas other TriPLE microspheres did not show any changes in crystallinity. Therefore, the aggregation of TriPLE microspheres during EO gas sterilization was markedly reduced as the initial crystallinity of TriPLE in the microspheres was increased.     

Amphotericin B-loaded poly(ethylene glycol)-poly(lactide) micelles: preparation, freeze-drying, and in vitro release

Polymeric micelles prepared from a series of poly(ethylene glycol)-poly(lactide) (PEG-PLA) diblock copolymers with various PLA chain lengths were designed as drug carriers for water insoluble drug amphotericin B (AmB). Physicochemical properties of AmB-loaded micelles were evaluated. Micelles were freeze-dried to obtain long-time stable formulations. The redispersibility of the freeze-dried samples was poor when the weight ratio of PLA block was bigger than the PEG block of the copolymer. Various types of lyoprotectants including saccharides and PEGs with different molecular weight were tested to improve the redispersion performance of the freeze-dried samples. PEG was proved to be more effective than saccharides on stabilizing the micelles during lyophilization when the weight ratio of PLA block was bigger than PEG block. The sustained release in vitro of AmB was evidenced. About 80% of AmB was released in 80 h. The in vitro release behavior could be best described by the first-order equation. The release rate was reduced as enhancing PLA chain length due to the stronger interaction between poorly water-soluble AmB and longer hydrophobic chain length of PLA.     

Synthesis and characterization of poly(ethylene glycol)-poly(D,L-lactide-co-glycolide) poly(ethylene glycol) tri-block co-polymers modified with collagen: a model surface suitable for cell interaction

This study focused on the synthesis and characterization of poly(ethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) tri-block co-polymer (PEG-PDLLG-PEG), and its modification with type-I collagen. To this aim, a PEG-PDLLG-PEG tri-block co-polymer was synthesized in two steps by reacting poly(ethylene glycol)bis(carboxymethyl)ether with thionyl chloride to obtain an acyl-halide-terminated poly(ethylene glycol) and subsequently coupling this compound to hydroxyl-terminated poly(D,L-lactide-co-glycolide) (PDLLG). The new carboxyl endgroups of PEG-PDLLG-PEG were subsequently reacted with N-hydroxysuccinimide (NHS) in the presence of the hetero-bifunctional cross-linking agent dicyclohexylcarbodiimide (DCC) in order to activate the co-polymer for coupling with collagen. PEG-PDLLG-PEG and its activated form PEG-PDLLG-NHS were characterized by Fourier transform infrared (FT-IR) and 1H-NMR spectroscopy. Molecular weights of the polymeric products were determined by SEC. Type-I collagen in phosphate buffer was reacted with PEG-PDLLG-NHS. The resultant product, PEG-PDLLG-Col, was characterized by FT-IR. This biopolymer was used for preparation of a suitable surface for cell growth experiment. To measure the degree of cell proliferation, the films prepared with PDLLG, PEG-PDLLG-NHS and PEG-PDLLG-Col were seeded with L929 mouse fibroblasts. Cell growth was followed by SEM photography and quantitated by the neutral red uptake assay. It was shown that the attachment of collagen significantly increased the number of cells on the co-polymers.     

Synthesis and polymerization of poly(ethylene glycol) fumarates

Fumaric esters of poly(ethylene glycol) ( 1a–d ) were prepared as macromonomers. The halfesters 1a and 1c were obtained by interaction of maleic anhydride with the monoethers of poly(ethylene glycol) ( 2a and 2b ) in the presence of 4-dimethylaminopyridine, and the diesters 1b and 1d by esterification of methyl hydrogen fumarate ( 13 ) with the monoethers of poly(ethylene glycol) ( 2a and 2b ). The macromonomers were found to homopolymerize and to copolymerize with styrene and methyl methacrylate following a radical polymerization mechanism.     

Functionalization of poly(ethylene glycol) and monomethoxy-poly(ethylene glycol)

Simple methods are described for the substitution of poly(ethylene glycol) and monomethoxy-poly(ethylene glycol) substitution. Affinity ligands, coenzymes, or enzymes can be covalently attached to the substitution product or they can be used as liquid ionexchangers.     

The in vivo and in vitro degradation behavior of poly(trimethylene carbonate)

The in vivo and in vitro degradation behavior of poly(trimethylene carbonate) (PTMC) polymers with number average molecular weights of 69 x 10(3), 89 x 10(3), 291 x 10(3) and 457 x 10(3)g/mol (respectively abbreviated as PTMC(69), PTMC(89), PTMC(291) and PTMC(457)) was investigated in detail. PTMC rods (3mm in diameter and 4mm in length) implanted in the femur and tibia of rabbits degraded by surface erosion. The mass loss of high molecular weight PTMC(457) specimens was 60wt% in 8 wks, whereas the mass loss of the lower molecular weight PTMC(89) specimens in the same period was 3 times lower. PTMC discs of different molecular weights immersed in lipase solutions (lipase from Thermomyces lanuginosus) degraded by surface erosion as well. The mass and thickness of high molecular weight PTMC(291) discs decreased linearly in time with an erosion rate of 6.7 microm/d. The erosion rate of the lower molecular weight PTMC(69) specimens was only 1.4mum/d. It is suggested that the more hydrophilic surface of the PTMC(69) specimens prevents the enzyme from acquiring a (hyper)active conformation. When PTMC discs were immersed in media varying in pH from 1 to 13, the non-enzymatic hydrolysis was extremely slow for both the high and low molecular weight samples. It can be concluded that enzymatic degradation plays an important role in the surface erosion of PTMC in vivo.     

Nanoparticles of poly(D,L-lactide)/methoxy poly(ethylene glycol)-poly(D,L-lactide) blends for controlled release of paclitaxel

Paclitaxel is one of the best antineoplastic drugs found in nature in the past decades, which has excellent therapeutic effects against a wide spectrum of cancers. Because of its high hydrophobicity, Cremophor EL has to be used as adjuvant in its clinical dosage form (Taxol), which has been found to cause serious side effects. Nanoparticles of biodegradable polymers may provide an ideal solution. In this research, paclitaxel-loaded nanoparticles of poly(D,L-lactide)/methoxy poly(ethylene glycol)-polylactide (PLA/MPEG-PLA) blends of various blend ratio 100/0, 75/25, 50/50, 25/75, and 0/100 were formulated by the nanoprecipitation method for controlled release of paclitaxel. It was found that increasing the proportion of MPEG-PLA component in the blend from 0 to 100% resulted in a progressive decrease of the particle size from 230.6+/-11.1 nm to 74.8+/-14.0 nm. The zeta potential of the drug-loaded nanoparticles was increased accordingly from -19.60+/-1.13 mV to a nearly neutral, that is, -0.33+/-0.28 mV, which indicates the gradual enrichment of PEG segments on the particle surface. The findings were further confirmed by X-Ray Photoelectron Spectroscopy (XPS) analysis. Differential scanning calorimetry (DSC) analysis showed that the glass transition temperature of PLA was significantly decreased from 58.7 to 52.1 degrees C with an increase of MPEG-PLA proportion from 0 to 75%, suggesting the miscibility of PLA and MPEG-PLA. The pure PLA nanoparticles (100/0) exhibited the slowest drug-release rate with 37.3% encapsulated drug released from the nanoparticles for 14 days while the MPEG-PLA nanoparticles (0/100) achieved the fastest drug release with 95.9% drug release in the same period.