pH-responsive polymeric micelles of poly(ethylene glycol)-b-poly(alkyl(meth)acrylate-co-methacrylic acid): influence of the copolymer composition on self-assembling properties and release of candesartan cilexetil.

The objective of the present study was to investigate the influence of chemical structure and molecular weight of pH-sensitive block copolymers on their self-assembling properties, the loading and the release of candesartan cilexetil (CDN). Block copolymers of poly(ethylene glycol) and t-butyl methacrylate, iso-butyl acrylate, n-butyl acrylate or propyl methacrylate were synthesized by atom transfer radical polymerization. pH-sensitivity was obtained by hydrolysis of t-butyl groups. The poorly water-soluble drug CDN was incorporated in the micelles and the in vitro drug release was evaluated as a function of pH. The critical aggregation concentration of hydrolyzed copolymers (pK(a)=6.2-6.6) was higher compared to the unhydrolyzed ones. Dynamic light scattering studies and atomic force microscopy images revealed uniform size micelles with aggregation numbers ranging from 60 to 160. The entrapment efficiency of CDN was generally found to be above 90%, with drug loading levels reaching approximately 20% (w/w). Differential scanning calorimetry studies showed the amorphous nature of entrapped CDN. The release of CDN from pH-sensitive micelles was triggered upon an increase in pH from 1.2 to 7.2. These findings suggest that the PEG-b-poly(alkyl(meth)acrylate-co-methacrylic acid)s can self-assemble to form micelles which exhibit high loading capacities for CDN and release the drug in a pH-dependent fashion.     

Controlled release solid dosage forms using combinations of (meth)acrylate copolymers

Controlled release solid oral dosage forms have been widely used for decades, enabling drugs to be administered more comfortably while at the same time providing a sustained and reproducible method of release. (Meth)acrylate copolymers are one of the options available when considering a sustained release solid form. Due to their different functionalities it is possible to achieve various different release profiles. The electrical character of these copolymers and their pH-dependent solubility can result in new and modified patterns when these polymers are combined. This review sheds light on various studies involving combinations of (meth)acrylate copolymers for use in multi-unit systems and matrix tablets, and also on several analytical methods that help to identify possible interactions between these polymers.     

Controlled Release Solid Dosage Forms Using Combinations of (meth)acrylate Copolymers

Controlled release solid oral dosage forms have been widely used for decades, enabling drugs to be administered more comfortably while at the same time providing a sustained and reproducible method of release. (Meth)acrylate copolymers are one of the options available when considering a sustained release solid form. Due to their different functionalities it is possible to achieve various different release profiles. The electrical character of these copolymers and their pH-dependent solubility can result in new and modified patterns when these polymers are combined. This review sheds light on various studies involving combinations of (meth)acrylate copolymers for use in multi-unit systems and matrix tablets, and also on several analytical methods that help to identify possible interactions between these polymers.     

Application of polyethylene glycol (PEG) to the control of permeability of poly(meth)acrylate coatings

Pellets with pholedrine sulphate are coated by means of a fluid-bed process with poly(meth)acrylate materials (Eudragit RS, Eudragit E 30 D, Scopacryl D 340) and varying portions of PEG 6000. In addition to influencing drug release by change of the thickness it was studied the admixture of PEG to the films. Figure logarithm permeability coefficient vs. the portion of PEG can be used to select a coating composition with wished permeability. By application of aqueous latex dispersions (Eudragit E 30 D, Scopacryl D 340) PEG dissolves completely very fast from the coatings. On the other hand if organic lac solution (Eudragit RS) is used a stagnation of the dissolution process after some min is observed. By leaching out the PEG the structure of the resulting films is loosened and therefore its permeability is increased.     

Interpolymer combinations of chemically complementary grades of Eudragit copolymers: a new direction in the design of peroral solid dosage forms of drug delivery systems with controlled release (review)

Principles of the combination of chemically complementary grades of Eudragit? copolymers in peroral, matrix, and reservoir types of solid dosage forms with modified release [tablets, microspheres, (micro)pellets] and their manufacturing technology (including film coatings) are considered. Modified drug release is achieved due to the interaction between reactive groups of copolymer pairs, which controls the drug release process both inside matrices and within multilayers or combined coatings. Analysis of these processes has key significance for developing (meth)acrylate polycomplexes, which could be synthesized in both aqueous and organic media, as new classes of drug carriers for constructing modern peroral drug delivery systems.     

Thermosensitive mPEG-b-PA-g-PNIPAM Comb Block Copolymer Micelles: Effect of Hydrophilic Chain Length and Camptothecin Release Behavior

Purpose

Block copolymer micelles are extensively used as drug controlled release carriers, showing promising application prospects. The comb or brush copolymers are especially of great interest, whose densely-grafted side chains may be important for tuning the physicochemical properties and conformation in selective solvents, even in vitro drug release. The purpose of this work was to synthesize novel block copolymer combs via atom transfer radical polymerization, to evaluate its physicochemical features in solution, to improve drug release behavior and to enhance the bioavailablity, and to decrease cytotoxicity.

Methods

The physicochemical properties of the copolymer micelles were examined by modulating the composition and the molecular weights of the building blocks. A dialysis method was used to load hydrophobic camptothecin (CPT), and the CPT release and stability were detected by UV–vis spectroscopy and high-performance liquid chromatography, and the cytotoxicity was evaluated by MTT assays.

Results

The copolymers could self-assemble into well-defined spherical core-shell micelle aggregates in aqueous solution, and showed thermo-induced micellization behavior, and the critical micelle concentration was 2.96–27.64 mg L^?1. The micelles were narrow-size-distribution, with hydrodynamic diameters about 128–193 nm, depending on the chain length of methoxy polyethylene glycol (mPEG) blocks and poly(N-isopropylacrylamide) (PNIPAM) graft chains or/and compositional ratios of mPEG to PNIPAM. The copolymer micelles could stably and effectively load CPT but avoid toxicity and side-effects, and exhibited thermo-dependent controlled and targeted drug release behavior.

Conclusions

The copolymer micelles were safe, stable and effective, and could potentially be employed as CPT controlled release carriers.     

Thermosensitive Hydrogels Composed of Hyaluronic Acid and Gelatin as Carriers for the Intravesical Administration of Cisplatin

The aim of this work was to evaluate the use of thermosensitive hydrogels for intravesical cisplatin delivery into the bladder. Poly(N-isopropylacrylamide) (PNIPAM) was grafted onto hyaluronic acid (HA) to synthesize an HPN copolymer, which was further grafted with gelatin to form an HPNG copolymer. A 3% concentration of HPN and HPNG was sufficient to exert a thermosensitive response, whereas a concentration of 8% was needed for PNIPAM to form the hydrogel. The physicochemical and drug delivery properties were examined by scanning electron microscopy (SEM), the lower critical solution temperature (LCST), hydration ratio, and in vitro cisplatin release. The incorporation of HA and gelatin produced a different microstructure compared to the parent PNIPAM hydrogel. Gelatin conjugation increased the fibrous structure in the matrix. The LCSTs of PNIPAM, HPN, and HPNG were 32.3, 32.0, and 30.7°C, respectively. The copolymers showed an eightfold increase in the hydration capacity compared to PNIPAM, with no significant difference in values between HPN and HPNG. The release of cisplatin from an aqueous solution (control) was nearly complete after 8 h, compared to 85, 80, and 52% release from PNIPAM, HPN, and HPNG, respectively. In vivo evaluation of cisplatin levels in bladder tissues was performed following intravesical instillation in rats. When the dwell time was extended to 6 h, PNIPAM showed a sevenfold enhancement in the drug concentration in the bladder wall. HPNG also showed a twofold increase in the drug concentration. The administration of cisplatin by the HPN carrier did not change the drug accumulation compared to the control. Confocal laser scanning microscopic results confirmed the trend of drug absorption from various systems. A histological examination showed no adverse change in the urothelium with HPN or HPNG application. PNIPAM caused partial desquamation of umbrella cells. The thermosensitive hydrogels prepared in this study may be promising carriers for targeted drug delivery to the bladder.     

Versatile polyion complex micelles for peptide and siRNA vectorization to engineer tolerogenic dendritic cells

Dendritic cells (DCs) are professional antigen-presenting cells that play a critical role in maintaining the balance between immunity and tolerance and, as such are a promising immunotherapy tool to induce immunity or to restore tolerance. The main challenge to harness the tolerogenic properties of DCs is to preserve their immature phenotype. We recently developed polyion complex micelles, formulated with double hydrophilic block copolymers of poly(methacrylic acid) and poly(ethylene oxide) blocks and able to entrap therapeutic molecules, which did not induce DC maturation. In the current study, the intrinsic destabilizing membrane properties of the polymers were used to optimize endosomal escape property of the micelles in order to propose various strategies to restore tolerance. On the first hand, we showed that high molecular weight (Mw) copolymer-based micelles were efficient to favor the release of the micelle-entrapped peptide into the endosomes, and thus to improve peptide presentation by immature (i) DCs. On the second hand, we put in evidence that low Mw copolymer-based micelles were able to favor the cytosolic release of micelle-entrapped small interfering RNAs, dampening the DCs immunogenicity. Therefore, we demonstrate the versatile use of polyionic complex micelles to preserve tolerogenic properties of DCs. Altogether, our results underscored the potential of such micelle-loaded iDCs as a therapeutic tool to restore tolerance in autoimmune diseases.     

Increasing entrapment of peptides within poly(alkyl cyanoacrylate) nanoparticles prepared from water-in-oil microemulsions by copolymerization

Low molecular hydrophilic actives such as peptides are typically poorly encapsulated within poly(alkyl cyanoacrylate) nanoparticles when prepared from micellar or microemulsion templates. The aim of the present study was to investigate whether the entrapment of peptides within poly(alkyl cyanoacrylate) nanoparticles could be increased by functionalizing the peptide so that it could copolymerize with the alkyl cyanoacrylate monomer. Peptide and acryloyl functionalized peptide representing the antigenic epitope of the lymphocytic choriomeningitis virus glycoprotein (LCMV(33-41)) were synthesized using solid-phase peptide synthesis. Poly(alkyl cyanoacrylate) nanoparticles were prepared to encapsulate either peptide or functionalized peptide using both an aqueous micellar and a water-in-oil microemulsion polymerization template. Using the micellar template, nanoparticles could not be produced in the presence of acryloyl peptide. Rather an agglomerated mass formed on the stirrer. In contrast, nanoparticles could be prepared using both acryloyl and parent peptide using the water-in-oil microemulsion template. Encapsulation efficiency was more than twofold greater for functionalized peptide, being greater than 90%. Encapsulation efficiency of functionalized peptide was also observed to increase with increasing the amount of alkyl cyanoacrylate monomer used for polymerization. A biphasic release profile was observed for the nanoparticles entrapping the non-functionalized peptide with greater than 50% of peptide being released during the first 10min and with around 90% being released at 6h. In contrast, less than 10% of the total amount of acryloyl LCMV(33-41) entrapped within the nanoparticles was detected in the release media following the initial 10min, and no further release of peptide was observed up to the termination of the release study at 360min. The difference in entrapment and release kinetics between the parent and functionalized peptide strongly supports the presumption that most of the acryloyl peptide actually intervened in the copolymerization with alkyl cyanoacrylate monomer and was covalently bound within the nanoparticles instead of being physically entrapped or adsorbed which appeared to be the case for the parent peptide. Thus, functionalizing a peptide so that it can copolymerize with the alkyl cyanoacrylate monomer is a strategy which can be used to increase the entrapment efficiency of peptides within poly(alkyl cyanoacrylate) nanoparticles and also maintain the peptide associated with nanoparticles so that the benefits of nanoparticulate delivery can be exploited.     

Amino acid based amphiphilic copolymer micelles as carriers of non-steroidal anti-inflammatory drugs: solubilization, in vitro release and biological evaluation

Three novel amino acid based anionic amphiphilic copolymers poly(sodium N-acryloyl-l-valinate-co-alkylacrylamide) (where, alkyl=octyl and dodecyl) with either 9 or 16 mol% hydrophobic substitution were synthesized. These hydrophobically modified polyelectrolytes (HMPs), above a critical concentration, self-assemble in aqueous solution through inter-chain hydrophobic aggregation, forming micelle-like aggregates having hydrodynamic diameter in the range of 50-200 nm. The HMPs were found to undergo conformational changes with the change in solution pH, electrolyte and additive concentration, and temperature. The polymeric micelles were observed to be stable under biological conditions (pH 7.4, [NaCl]=150 mM and temperature (37°C)). The solubilization capacity of the polymeric micelles for six important non-steroidal anti-inflammatory drugs of different hydrophobicity was evaluated. Depending upon the hydrophobicity the solubilities of the drugs were observed to increase ca. 2-10 times in the presence of 1.0 g/L copolymers. The in vitro release kinetics of the loaded drug was studied under physiological pH. To explore their potential application in pharmaceutical industries hemocompatibility and cytotoxicity studies were carried out using hemolytic and MTT assay, respectively. The anionic HMPs were found to be not directly toxic to mammalian cells.     

Dunkerque City air pollution particulate matter-induced cytotoxicity, oxidative stress and inflammation in human epithelial lung cells (L132) in culture.

Exposure to urban airborne particulate matter (PM) has been associated with adverse health effects. In this work, we focused our attention on the capacity of air pollution PM to induce cytotoxic, oxidative stress, and inflammatory responses in human epithelial lung cells (L132) in culture. PM were collected in Dunkerque, a French seaside city, and their physical and chemical characteristics were carried out. Their size distribution showed that 92.15% of the PM were equal or smaller than 2.5 and their specific surface area was 1 m2/g. Inorganic (i.e. Fe, Al, Ca, Na, K, Mg, Pb, etc.) and organic (i.e. VOC, PAH, etc.) chemicals were found in PM. Physical and chemical properties of Dunkerque City's PM suggested that much of the collected PM derived from wind-borne dust from the industrial complex and the heavy motor vehicle traffic. Their cytotoxicity, as evaluated by survival rate determination, lactate dehydrogenase activity, and mitochondrial dehydrogenase activity showed concentration and time-dependent effects in L132 cells (LC10 = 18.84 microg PM/ml; LC50 = 75.36 microg PM/ml). Moreover, in PM-exposed L132 cells, there were concentration- and time-dependent changes in lipid peroxidation, superoxide dismutase activity, 8-hydroxy-2'-deoxyguanosine formation, and poly(ADP-ribosyl)ation, on the one hand, and in tumor necrosis factor-alpha secretion, inducible nitric oxide synthase activity, and nitric oxide release, on the other hand. Taken together, these findings suggested that oxidative stress and inflammatory responses proceeded cytotoxicity in PM-exposed L132 cells.     

Preparation and characterization of pH-responsive polymeric micelles for the delivery of photosensitizing anticancer drugs

pH-responsive polymeric micelles (PM) consisting of random copolymers of N-isopropylacrylamide (NIPA), methacrylic acid (MAA), and octadecyl acrylate (ODA) were prepared and characterized. The critical aggregation concentration, as determined by a fluorescence probe technique, was approximately 10 mg/L in water and phosphate-buffered saline. Phase transition pH was estimated at 5.7. The decrease in pH was accompanied by the destruction of hydrophobic clusters. Micelle size was dependent on temperature and the nature of the aqueous medium. The micelles were successfully loaded with a substantial amount of a photoactive anticancer drug, namely, aluminum chloride phthalocyanine (AlClPc). pH-responsive PM loaded with AlClPc were found to exhibit higher cytotoxicity against EMT-6 mouse mammary cells in vitro than control Cremophor EL formulation. These results show the potential of poly(NIPA-co-MAA-co-ODA) for in vivo administration of water-insoluble, photosensitizing anticancer drugs.     

Design of sustained release fine particles using two-step mechanical powder processing: Particle shape modification of drug crystals and dry particle coating with polymer nanoparticle agglomerate

We attempted to prepare sustained release fine particles using a two-step mechanical powder processing method; particle-shape modification and dry particle coating. First, particle shape of bulk drug was modified by mechanical treatment to yield drug crystals suitable for the coating process. Drug crystals became more rounded with increasing rotation speed, which demonstrates that powerful mechanical stress yields spherical drug crystals with narrow size distribution. This process is the result of destruction, granulation and refinement of drug crystals. Second, the modified drug particles and polymer coating powder were mechanically treated to prepare composite particles. Polymer nanoparticle agglomerate obtained by drying poly(meth)acrylate aqueous dispersion was used as a coating powder. The porous nanoparticle agglomerate has superior coating performance, because it is completely deagglomerated under mechanical stress to form fine fragments that act as guest particles. As a result, spherical drug crystals treated with porous agglomerate were effectively coated by poly(meth)acrylate powder, showing sustained release after curing. From these findings, particle-shape modification of drug crystals and dry particle coating with nanoparticle agglomerate using a mechanical powder processor is expected as an innovative technique for preparing controlled-release coated particles having high drug content and size smaller than 100 μm.     

Isobornyl acrylate: an impurity in alkyl glucosides

Context: Alkyl glucosides and alkyl poly-glucosides are widely used as wetting agents, surfactants and emulsifiers in several industrial and cosmetic products. They are known as well-tolerated and are usually added to the primary surfactants in order to reduce the irritating potential of the main foaming agents.

Objective: Recently, some authors suggested that allergic contact dermatitis to alkyl glucosides might be more frequent than suspected. On the other hand, the chemical structures of glucosides do not show potentially allergenic chemical groups or strongly polarized structures. The aim of our study is to investigate alkyl glucosides carrying out a detailed chemical analysis on samples of raw materials to identify potentially allergenic impurities or by-products contained in commercial samples of alkyl glucosides.

Materials and methods: We chemically analyzed samples of cocoyl glucoside, decyl glucoside and lauryl glucoside by three different analytical methods, in order to identify any undesired or polluting substances.

Result: In each of the three samples, we detected the presence of isobornyl acrylate. Its approximate content in the tested samples is 500?ng/g of the product.

Discussion: Isobornyl acrylate is not used in the synthesis of alkyl glucosides, but as a plasticizer in many plastic materials. It can be easily released to materials flowing over these surfaces when they have high extraction power, as glucosides.

Conclusion: Isobornyl acrylate may play a role as hidden allergen, in the form of an impurity collected during the industrial process, explaining some cases of allergic reaction to alkyl glucosides.     

Nanostructure formation in aqueous solution of amphiphilic copolymers of 2-(N,N-dimethylaminoethyl)methacrylate and alkylacrylate: Characterization, antimicrobial activity, DNA binding, and cytotoxicity studies

Three amphiphilic random copolymers poly(2-(dimethylaminoethyl)methacrylate-co-alkylacrylate) (where, alkyl = hexyl, octyl, dodecyl) with 16 mol% hydrophobic substitution were synthesized. Surface tension, viscosity, fluorescence probe, dynamic light scattering (DLS), as well as transmission electron microscopic (TEM) techniques were utilized to investigate self-assembly formation by the hydrophobically modified polymers (HMPs) in pH 5. Formation of hydrophobic domains through inter-polymer chain interaction of the copolymer in dilute solution was confirmed by fluorescence probe studies. Average hydrodynamic diameter of the copolymer aggregates at different polymer concentration was measured by DLS studies. The copolymer with shorter hydrophobic chain exhibits larger hydrodynamic diameter in dilute solution, which decreased with either increase of concentration or increase of hydrophobic chain length. TEM images of the dilute solutions of the copolymers with shorter as well as with longer hydrophobic chain exhibit spherical aggregates of different sizes. The antimicrobial activity of the copolymers was evaluated by measuring the minimum inhibitory concentration value against one Gram-positive bacterium Bacillus subtilis and one Gram-negative bacterium Escherichia coli. The copolymer with the octyl group as pendent hydrophobic chain was found to be more effective in killing these microorganisms. The interaction of the cationic copolymers with calf-thymus DNA was studied by fluorescence quenching method. The polymer-DNA binding was found to be purely electrostatic in nature. The hydrophobes on the polymer backbone were found to have a significant influence on the binding process. Biocompatibility studies of the copolymers in terms of cytotoxicity measurements were finally performed at different concentrations of the HMPs to evaluate their potential application in biomedical fields.     

Poly(ethylene oxide) based copolymers: solubilisation capacity and gelation

It is thought that almost half of potentially useful drug candidates fail to progress to formulation development because of their low aqueous solubility and associated poor or erratic absorption characteristics. A response to this challenge has been the development of a variety of colloidal delivery systems in which the therapeutic agent is encapsulated in nanosized particles. In this review, attention is focussed on colloidal vectors based on amphiphilic block copolymers, the micelles of which can accommodate a wide range of water-insoluble guest molecules, and particularly on copolymers with poly(oxyethylene) as the hydrophilic block and with poly(oxyalkylene) or polyester hydrophobic blocks, taking advantage of the 'stealth' properties of the poly(oxyethylene) corona of their micelles. Although copolymers of this type have been commercially available for several decades in the form of the Pluronic (BASF) polyols, which have a poly(oxypropylene) hydrophobic block, they have not found wide application for drug solubilisation, primarily because of their low solubilisation capacity. In attempts to achieve greater drug loading, recent work has concentrated on copolymers in which the core-forming blocks are designed to be more hydrophobic and more compatible with the drug to be encapsulated. Progress in this area has been reviewed and recent developments in the design of block copolymers of this type that combine high drug loading capacity with thermally reversible gelation characteristics in the temperature range suitable for potential application as in situ gelling vehicles following subcutaneous injection have also been discussed.     

Nano-scaled pH-responsive polymeric vesicles for intracellular release of doxorubicin

Polymeric vesicles produced by spontaneous self-association of poly(acrylic acid-co-distearin acrylate) (poly(AAc-co-DSA)) with varying ratios of AAc and DSA units in aqueous solution of pH 5.0 exhibit the pH-regulated drug release behavior. Through the electrostatic interaction with ionized AAc residues, doxorubicin (DOX) molecules can be highly accommodated onto either the inner or outer surfaces of vesicles when the pH is adjusted from 5.0 to 7.4. The extent of DOX encapsulation is dependent largely on the structural transition of vesicles in response to the pH change. While the pH-evolved drug release profile varies to some extent with the distribution of DOX molecules within vesicles, the drug release from vesicles is accelerated significantly via the disruption of the electrostatic interaction of DOX species with ionized AAc moieties at pH 5.0. The DOX-loaded polymeric vesicles show promoted cellular uptake and cytotoxicity comparable to free DOX for HeLa cells. This indicates that they are probably taken up by the cells via the lipid raft-mediated endocytosis.     

Relationship of film properties to drug release from monolithic films containing adjuvants.

The rate of drug release from a polymeric matrix system was influenced by the physical and chemical properties of the monolithic films. The model drugs, salicylic acid and chlorpheniramine maleate, and two poly(methyl methacrylate) copolymers of different permeabilities (Eudragit RL and Eudragit RS), with and without additional adjuvants, were used to form monolithic matrix films for controlled drug release. Adjuvants, including polyethylene glycols (PEG 400 and PEG 8000) and poly(vinylpyrrolidones) (PVP-K15 and PVP-K90), were incorporated into films of Eudragit RL PM and Eudragit RS PM. The moisture permeation constant, glass transition temperature (Tg), tensile strength, and drug release profiles were determined for each acrylic resin slab to correlate the physicochemical and physicomechanical film properties to observed drug release. Faster rates of drug diffusion were observed with the addition of PEG 400 to the films, because of its plasticizing effect and the resultant increased moisture permeability of the matrix. An exception existed with the Eudragit RL PM film containing salicylic acid where drug-polymer interactions inhibited drug diffusion. The small changes in moisture permeability, Tg, and tensile strength observed with incorporation of the PVPs had an insignificant influence on the dissolution results for salicylic acid from Eudragit RS PM films. Increases in the tensile strength and Tg after addition of PVP to the Eudragit RS PM matrix support the observed decreased rate of diffusion for chlorpheniramine maleate. The pores formed by migration of the hydrophilic adjuvants from the films altered the diffusion kinetics of the matrix, compared with that of the nonporous polymer, when only the antihistamine was present.     

温度敏感性生物材料研究进展

目的：总结近年来温度敏感性生物材料（简称温敏材料）的研究进展,为后续温敏材料的进一步研究提供参考。方法：通过文献研究,总结目前常用的几种温敏材料的组成、原理,并介绍其在药物释放方面的应用。结果：温敏材料具有良好的生物相容性与低细胞毒性,常见的有壳聚糖聚合物、聚N-异丙基丙烯酰胺聚合物等,其温敏性决定了在药物释放中的作用,提高了药物靶向性。结论：温敏材料可受环境因素影响发生体积相变,是药物缓控释的优秀材料。设计性能优良的温敏材料并成功应用于临床将是未来的研究方向之一。     

The characterization of paclitaxel-loaded microspheres manufactured from blends of poly(lactic-co-glycolic acid) (PLGA) and low molecular weight diblock copolymers

Paclitaxel-loaded biodegradable drug delivery systems manufactured from poly(lactic-co-glycolic acid) (PLGA) are known to release the drug at extremely slow rates. The objective of this study was to characterize paclitaxel-loaded microspheres composed of blends of PLGA with low molecular weight ampipathic diblock copolymers. The encapsulation and release of a series of poly(epsilon-caprolactone) (PCL)- or poly(D,L-lactic acid) (PDLLA)-co-methoxypolyethylene glycol (MePEG) diblock copolymers was measured using quantitative gel permeation chromatography. Polymeric miscibility was determined by glass transition temperature measurements using differential scanning calorimetry and paclitaxel release was measured using HPLC methods. The PCL- and PDLLA-based diblock copolymers encapsulated at high efficiency and were miscible in PLGA microspheres (30-120m microm size range). The burst phase of paclitaxel release was increased up to 20-fold by the inclusion of diblock copolymers in PLGA microspheres. Approximately 10% of the more hydrophobic PCL-based copolymers released from the microspheres in a short burst over 3 days followed by very slow release over the following 10 weeks. Only the PDLLA-based copolymer released from the PLGA microspheres in a controlled manner over 10 weeks. All microspheres containing PEG were found to have more hydrophilic surfaces (as measured by contact angle) with improved biocompatibility (reduced neutrophil activation) compared to PLGA only microspheres. These results indicate that low molecular weight polyester-based diblock copolymers may be effectively encapsulated in PLGA microspheres to increase paclitaxel release (probably through a micellization process) and improve biocompatibility.