Preparation of biodegradable polymer nanoparticles by miniemulsion technique and their cell interactions

The emulsion/solvent evaporation method and miniemulsion technique were combined and applied in the formulation of biodegradable monodisperse nanoparticles at high solid contents using different biocompatible and biodegradable polymers such as poly(L-lactide) (PLLA), poly[(D,L-lactide)-co-glycolide] 50:50 (PLGA), and poly(epsilon-caprolactone) (PCL). Differences between the results of various polymers are found in terms of the particle size and size distribution as well as in the degradation time. An encapsulated hydrophobic fluorescent dye was used as a model marker in order to study the entrapment efficiency and diffusion yield out of the particle. Cellular uptake of the obtained particles was observed in Jurkat and HeLa cells. In the investigated particle size range of 80-200 nm, the surfactant on the particles' surface had a greater influence than the particle size. Uptake kinetics reveals that the PLLA and PCL particles are endocytosed much faster than polystyrene particles.     

Layer-by-layer polyelectrolyte coating of low molecular weight poly(lactic acid) nanoparticles

Low molecular weight (M(w)) poly(L-lactic acid) (PLA) nanoparticles were coated with polyelectrolytes (PEs) by layer-by-layer (LbL) technique using a filtration approach. Poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) were applied as PEs in coating. LbL coating is aimed to use in producing (nano)particulate drug delivery systems with improved biocompatibility and sustained or targeted release of drug substances. Nanoparticles of rapidly biodegradable polymers, like the low M(w) PLA, open up a possibility to control the release of the encapsulated substance by the coating, but set challenges to the coating process due to increased aggregation tendency and degradation rate of the polymer. When the core PLA nanoparticles were prepared by nanoprecipitation, surface properties of the nanoparticles were affected by solvent selection. Successful LbL coating of the PLA nanoparticles was obtained only with chloroform, but not with dichloromethane as the solvent during nanoprecipitation. Reason for this was found to be the more charged surface of the nanoparticles prepared with chloroform compared to the nanoparticles prepared with dichloromethane.     

Interaction of PLGA nanoparticles with human blood constituents

When nanoparticles are injected into the blood for drug delivery or drug detoxification, detrimental interaction of these particles with blood constituents must be avoided. In previous studies, the adsorption of albumin immunoglobulin G, and fibrinogen from blood plasma to a model hydrophobic polymer like polystyrene was investigated as was decreasing surface hydrophobicity, which quantitatively leads to decreasing amounts of adsorbed proteins on latex particles. However, the uptake of other blood constituents, such as inorganic blood electrolytes, by particles and the dispersion/coagulation characteristics of these particles in the blood stream have not been fully studied. Most importantly, the effect s of these particles on blood coagulation and hemolysis are not well known. In the present study, the poly(lactide-co-glycolide) acid(PLGA) nanoparticles were synthesized by using nanoprecipitation. The uptake of blood electrolytes from simulated blood fluid (SBF) and the stability (dispersion/aggregation) of nanoparticles in SBF was examined by using different loading amounts of PLGA and different contact time between PLGA nanoparticles and SBF. The interaction of particles with the organic components of blood was also studied by using the measurement of red blood cell hemolysis and blood clotting with raw PLGA, surfactant modified PLGA, and PEGylated PLGA.     

PLGA/TiO2纳米药物缓释载体的研究

首先利用硅烷偶联剂(KH550)对纳米二氧化钛表面进行预处理,得到氨基改性的二氧化钛,然后与带有高活性端基的丙交酯-乙交酯共聚物(PLGA)反应,制备纳米药物缓释载体PLGA/TiO2有机-无机杂化材料.通过核磁(1H-NMR)、傅里叶变换红外光谱仪(FTIR)、热重分析(TGA)、扫描电子显微镜(SEM)、透射电子显...     

Tunable self-assembled stereocomplexed-polylactic acid nanoparticles as a drug carrier

In this study, a model hydrophilic drug (porphyrin) was encapsulated within hydrophobic polylactic acid (PLA) nanoparticles (NPs) with different crystallinity and the relevant release behaviors were investigated. The crystalline modification was done using a modified nanoprecipitation method, where homo and stereocomplexed PLA NPs with different average diameters based on varying polymer concentrations and solvent/nonsolvent ratios (S/N) were prepared. Entrapment efficiency and drug release of sterocomplexed-PLA NPs were compared with neat poly(l -lactic acid) (PLLA) NPs. Furthermore, to get the more sustained release, porphyrin-loaded NPs were immobilized within electrospun poly(d ,l -lactide-co-glycolide (PLGA) nanofibers (NFs). Outcomes revealed that solution concentration and solvent/nonsolvent ratio play significant roles in the formation of homo and stereocomplexed NPs. On the other hand, it was found that the formation of stereocrystals did not significantly affect the size and morphology of NPs compared with neat NPs. With regard to the entrapment efficiency and drug content, stereocomplexd-PLA NPs behave relatively the same as neat PLLA NPs while the more sustained release was observed for stereocomplexed NPs. Also, it was observed that electrospinning of PLGA solution loaded by NPs led to the uniform distribution of NPs into PLGA fibers. Encapsulating the drug-loaded NPs into nanofibers decreased the rate of drug release by 50% after 24 h, compared with direct loading of drug into PLGA NFs. We conclude that it is possible to tune the entrapment efficiency and modify the release rate of the drug by giving small changes in the process parameters without altering the physical properties of the original drug substance and polymer.     

XPS and wettability characterization of modified poly(lactic acid) and poly(lactic/glycolic acid) films

Poly(lactic acid) (PLA) and poly(lactic/glycolic acid) copolymers (PLGA) are biodegradable drug carriers of great importance, although successful pharmaceutical application requires adjustment of the surface properties of the polymeric drug delivery system to be compatible with the biological environment. For that reason, reduction of the original hydrophobicity of the PLA or PLGA surfaces was performed by applying a hydrophilic polymer poly(ethylene oxide) (PEO) with the aim to improve biocompatibility of the original polymer. PEO-containing surfaces were prepared by incorporation of block copolymeric surfactants, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic), into the hydrophobic surface. Films of polymer blends from PLA or PLGA (with lactic/glycolic acid ratios of 75/25 and 50/50) and from Pluronics (PE6800, PE6400, and PE6100) were obtained by the solvent casting method, applying the Pluronics at different concentrations between 1 and 9.1% w/w. Wettability was measured to monitor the change in surface hydrophobicity, while X-ray photoelectron spectroscopy (XPS) was applied to determine the composition and chemical structure of the polymer surface and its change with surface modification. Substantial reduction of surface hydrophobicity was achieved on both the PLA homopolymer and the PLGA copolymers by applying the Pluronics at various concentrations. In accordance with the wettability changes the accumulation of Pluronics in the surface layer was greatly affected by the initial hydrophobicity of the polymer, namely, by the lactide content of the copolymer. The extent of surface modification was also found to be dependent on the type of blended Pluronics. Surface activity of the modifying Pluronic component was interpreted by using the solubility parameters.     

Enhanced gentamicin loading and release of PLGA and PLHMGA microspheres by varying the formulation parameters

The purpose of this study was to develop a suitable formulation for gentamicin sulfate (GS) that gives a sustained release of the drug. Therefore this drug was loaded into poly(D,L-lactide-co-glycolide) (PLGA) and poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres. The effects of various formulation parameters (ethanol, surfactant, osmotic value of the external phase, polymer type and concentration) on particle characteristics (size, loading and release) were investigated. The GS loaded microspheres were prepared using a double emulsion evaporation technique. The results demonstrate that neither ethanol nor surfactants had beneficial effects on the drug loading efficiency (around 4-10%). However, an increase in buffer concentration (and thus osmotic pressure) of the external phase resulted in a substantial increase of GS-loading (from 10 to 28%). Further, an increase of concentration of PLGA in DCM from 10% to 15/20% caused a 4-time increase of the drug loading. The best formulation identified in this study had a loading efficiency of around 70% resulting in PLGA microspheres with a 6% (w/w) loading. The particles showed a burst release of the drug depending on their porosity, followed by a phase of 35 days where hardly any release occurred. The drug was then slowly released for around 25 days likely due to degradation of the microspheres. The drug loading efficiency of GS in PLHMGA was not significantly different from PLGA microspheres (64%). The release of GS from PLHMGA microspheres was faster than that of PLGA because the degradation rate of PLHMGA is more rapid than PLGA. This study shows that prolonged release of gentamicin can be obtained by loading this drug into microspheres made of biodegradable aliphatic polyesters.     

Characterization and release of triptolide-loaded poly (d,l-lactic acid) nanoparticles

Triptolide (TP), which has immunosuppressive effect, anti-neoplastic activity, anti-fertility function and severe toxicities on digestive, urogenital, blood circulatory system, was used as a model drug in this study. TP-loaded poly (d,l-lactic acid) (PLA) nanoparticles were prepared by the modified spontaneous emulsification solvent diffusion method (modified-SESD method). Dynamic light scattering system (DLS), transmission electron microscope (TEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), X-ray powder diffractometry and Fourier transform infra-red spectroscopy (FT-IR) were employed to characterize the nanoparticles fabricated for size and size distribution, surface morphology, the physical state of drug in nanoparticles, and the interaction between the drug and polymer. Encapsulation efficiency (EE) and the in vitro release of TP in nanoparticles were measured by the reverse phase high-performance liquid chromatography (RP-HPLC). The produced nanoparticles exhibited a narrow size distribution with a mean size of approximately 150 nm and polydispersity index of 0.088. The morphology of the nanoparticles exhibited a fine spherical shape with smooth surfaces without aggregation or adhesion. TP-entrapped in nanoparticles was found in the form of amorphous or semicrystalline. It was found that a weak interaction existed between the drug and polymer. In all experiments, more than 65% of EE were obtained. The in vitro release profile of TP from nanoparticles exhibited a typical biphasic release phenomenon, namely initial burst release and consequently sustained release. In this case, the particle size played an important role for the drug release. The modified-SESD method was a potential and advantage method to produce an ideal polymer nanoparticles for drug delivery system (DDS).     

Poly(alkylcyanoacrylate) colloidal particles as vehicles for antitumour drug delivery: a comparative study

Because of the fundamental importance of new therapeutic routes for cancer treatment, a number of systems based on colloidal particles as vehicles for the delivery of chemotherapeutic agents have been devised. The target is always to provide the proper dose of the antitumour agent only at the desired locus of action, thus reducing the unwanted side effects. The systems studied in this work are nanospheres of the biodegradable polymers poly(ethyl-2-cyanoacrylate), poly(butylcyanoacrylate), poly(hexylcyanoacrylate) and poly(octylcyanoacrylate), all suitable for parenteral administration, as vehicles for 5-fluorouracil, a well studied drug used for the treatment of solid tumours. Two loading methods have been analyzed: the first one is based on drug addition during the process of generation of the particles, by an anionic emulsion/polymerization procedure, and the subsequent drug trapping in the polymeric network. The second method is based on surface adsorption in already formed nanoparticles, after incubation in the drug solution. A detailed investigation of the capabilities of the polymer particles to load this drug is described. The main factors determining the drug incorporation to the polymer network were the type of monomer, the pH and the drug concentration. The release kinetics of 5-fluorouracil is found to be controlled by the pH of the release medium, the type of drug incorporation and the type of polymer.     

Preparation, characterization and application of pyrene-loaded methoxy poly(ethylene glycol)–poly(lactic acid) copolymer nanoparticles

Pyrene-loaded biodegradable polymer nanoparticles were prepared by incorporating pyrene into the polymer nanoparticles formulated from amphiphilic diblock copolymer, methoxy poly(ethylene glycol)–poly(lactic acid) (MePEG–PLA). Their morphological structure and physical properties were characterized by nuclear magnetic resonance (NMR), dynamic light scattering, fluorescence spectroscopy, transmission electronic microscopy and zeta potential measurements. Further, MePEG–PLA nanoparticles containing pyrene as fluorescent marker were administered intranasally to rats, and the distribution of nanoparticles in the nasal mucosa and the olfactory bulb were visualized by fluorescence microscopy. NMR results confirmed that MePEG–PLA copolymer can form nanoparticles in water, and hydrophilic PEG chains were located on the surface of the nanoparticles. The particle size, zeta potential and pyrene loading efficiency of MePEG–PLA nanoparticles were dependent on the PLA block content in the copolymer. Following nasal administration, the absorption of nanoparticles across the epithelium was rapid, with fluorescence observed in the olfactory bulb at 5 min, and a higher level of fluorescence persisted in the olfactory mucosa than that in the respiratory mucosa. These results show that pyrene could serve as a useful fluorescence probe for incorporation into polymer nanoparticles to study tissue distribution and MePEG–PLA nanoparticles might have a great potential as carriers of hydrophobic drugs.     

'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption

Nanoparticles possessing poly(ethylene glycol) (PEG) chains on their surface have been described as blood persistent drug delivery system with potential applications for intravenous drug administration. Considering the importance of protein interactions with injected colloidal dug carriers with regard to their in vivo fate, we analysed plasma protein adsorption onto biodegradable PEG-coated poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(-caprolactone) (PCL) nanoparticles employing two-dimensional gel electrophoresis (2-D PAGE). A series of corona/core nanoparticles of sizes 160–270 nm were prepared from diblock PEG-PLA, PEG-PLGA and PEG-PCL and from PEG-PLA:PLA blends. The PEG Mw was varied from 2000–20 000 g/mole and the particles were prepared using different PEG contents. It was thus possible to study the influence of the PEG corona thickness and density, as well as the influence of the nature of the core (PLA, PLGA or PCL), on the competitive plasma protein adsorption, zeta potential and particle uptake by polymorphonuclear (PMN) cells. 2-D PAGE studies showed that plasma protein adsorption on PEG-coated PLA nanospheres strongly depends on the PEG molecular weight (Mw) (i.e. PEG chain length at the particle surface) as well as on the PEG content in the particles (i.e. PEG chain density at the surface of the particles). Whatever the thickness or the density of the corona, the qualitative composition of the plasma protein adsorption patterns was very similar, showing that adsorption was governed by interaction with a PLA surface protected more or less by PEG chains. The main spots on the gels were albumin, fibrinogen, IgG, Ig light chains, and the apolipoproteins apoA-I and apoE. For particles made of PEG-PLA45K with different PEG Mw, a maximal reduction in protein adsorption was found for a PEG Mw of 5000 g/mole. For nanospheres differing in their PEG content from 0.5 to 20 wt %, a PEG content between 2 and 5 wt % was determined as a threshold value for optimal protein resistance. When increasing the PEG content in the nanoparticles above 5 wt % no further reduction in protein adsorption was achieved. Phagocytosis by PMN studied using chemiluminescence and zeta potential data agreed well with these findings: the same PEG surface density threshold was found to ensure simultaneously efficient steric stabilization and to avoid the uptake by PMN cells. Supposing all the PEG chains migrate to the surface, this would correspond to a distance of about 1.5 nm between two terminally attached PEG chains in the covering ‘brush’. Particles from PEG5K-PLA45K, PEG5K-PLGA45K and PEG5K-PCL45K copolymers enabled to study the influence of the core on plasma protein adsorption, all other parameters (corona thickness and density) being kept constant. Adsorption patterns were in good qualitative agreement with each other. Only a few protein species were exclusively present just on one type of nanoparticle. However, the extent of proteins adsorbed differed in a large extent from one particle to another. In vivo studies could help elucidating the role of the type and amount of proteins adsorbed on the fate of the nanoparticles after intraveinous administration, as a function of the nature of their core. These results could be useful in the design of long circulating intravenously injectable biodegradable drug carriers endowed with protein resistant properties and low phagocytic uptake.     

Sustained release of nucleic acids from polymeric nanoparticles using microemulsion precipitation in supercritical carbon dioxide

A general approach for producing biodegradable nanoparticles for sustained nucleic acid release is presented. The nanoparticles are produced by precipitating a water-in-oil microemulsion in supercritical CO(2). The microemulsion consists of a transfer RNA aqueous solution (water phase), dichloromethane containing poly(l-lactic acid)-poly(ethylene glycol) (oil phase), the surfactant n-octyl β-D-glucopyranoside, and the cosurfactant n-butanol.     

Plasma surface modification of poly (l-lactic acid) and poly (lactic-co-glycolic acid) films for improvement of nerve cells adhesion

Radio frequency (RF) plasma treatment in O₂ was applied to modify the surface of poly (l-lactic acid) (PLLA) and poly (d,l-lactic acid-coglycolic acid) (PLGA) as biodegradable polymers. The surface structure, morphology, wettability and surface chemistry of treated films were characterized by water drop contact angle measurement, scanning electron microscope (SEM), optical invert microscope, differential scanning calorimetry (DSC) and ATIR–FTIR spectroscopy. The cell affinity of the oxygen plasma treated film was evaluated by nervous tissue B65 cell culture in stationary conditions. The results showed that the hydrophilicity increased greatly after O₂ plasma treatment. The results showed that improved cell adhesion was attributed to the combination of surface chemistry and surface wettability during plasma treatment. Cell culture results showed that B65 nervous cell attachment and growth on the plasma treated PLLA was much higher than an unmodified sample and PLGA. Surface hydrophilicity and chemical functional groups with high polar component play an important role in enhancing cell attachment and growth.     

Study of the Air-Water Interfacial Properties of Biodegradable Polyesters and Their Block Copolymers with Poly(ethylene glycol)

It has been reported that the surface pressure-area isotherm of poly(d,l-lactic acid-ran-glycolic acid) (PLGA) at the air-water interface exhibits several interesting features: (1) a plateau at intermediate compression levels, (2) a sharp rise in surface pressure upon further compression, and (3) marked surface pressure-area hysteresis during compression-expansion cycles. To investigate the molecular origin of this behavior, we conducted an extensive set of surface pressure and AFM imaging measurements with PLGA materials having several different molecular weights and also a poly(d,l-lactic acid-ran-glycolic acid-ran-caprolactone) (PLGACL) material in which the caprolactone monomers were incorporated as a plasticizing component. The results suggest that (i) the plateau in the surface pressure-area isotherm of PLGA (or PLGACL) occurs because of the formation (and collapse) of a continuous monolayer of the polymer under continuous compression; (ii) the PLGA monolayer becomes significantly resistant to compression at high compression because under that condition the collapsed domains become large enough to become glassy (such behavior was not observed in the nonglassy PLGACL sample); and (iii) the isotherm hysteresis is due to a coarsening of the collapsed domains that occurs under high-compression conditions. We also investigated the monolayer properties of PEG-PLGA and PEG-PLGACL diblock copolymers. The results demonstrate that the tendency of PLGA (or PLGACL) to spread on water allows the polymer to be used as an anchoring block to form a smooth biodegradable monolayer of block copolymers at the air-water interface. These diblock copolymer monolayers exhibit protein resistance.     

聚乳酸载药微球制备及释药性能研究最新进展

对可生物降解材料聚乳酸作为药物载体制备微球制剂的研究状况进行了综述。针对目前限制聚乳酸微球制剂临床应用存在的问题,重点介绍了降低药物突释,提高药物包封率,改善多肽和蛋白药物微球释药性能等方面研究的最新进展。聚乳酸载药微球在药物传输中有着广阔的研究和应用前景。     

PEG-PLA block copolymer as potential drug carrier: preparation and characterization

Diblock and multiblock copolymers composed of a poly(D,L-lactide) (PLA) or poly(trimethylene carbonate) (PTMC) core with a hydrophilic chain of poly(ethylene glycol) (PEG) were prepared. These copolymers, in which the core is connected to PEG through a polyfunctional molecule such as citric, mucic, or tartaric acid, may be used to form nanoparticles for drug delivery applications. Branched copolymers were prepared by direct amidation between the polyfunctional acid and methoxy PEGamine, followed by ring-opening polymerization of lactide or trimethyl carbonate to form the PLA and PTMC block copolymers. In addition, a complex multiblock copolymer of biotin-PEG-poly[lactic-co-(glycolic acid)] (PLGA) for application in an avidin-biotin system was prepared for possible design of nanospheres with targeting properties. Studies of drug release from polymeric systems containing multiblock copolymers and studies of polymer degradation were also performed.     

Study of types and mixture ratio of organic solvent used to dissolve polymers for preparation of drug-containing PLGA microspheres

The effects of the types and the ratios of various organic solvents used as a mixtures to dissolve poly (lactide-co-glycolide) (PLGA) by using a solvent evaporation method, a technique used to prepare polymer particles, were carefully studied in order to investigate their advantages in developing drug delivery system (DDS) formulations for the prepared microspheres. The particle size and drug loading efficiency of drug-containing PLGA microspheres were found to be dependent on the types of solvent used due to the interfacial tension between the organic solvent and water phase. The drug loading efficiency of monodisperse microspheres prepared by using a membrane emulsification technique employing organic solvents and high interfacial tension for dissolving the PLGA was increased in a controlled manner. The organic solvents with high interfacial tension in the water phase used for the preparation of polymer particles by means of the solvent evaporation method were found to be suitable in terms of improvement in the properties of DDS formulations.     

Hydrolytic degradation of poly(rac‐lactide) and poly[(rac‐lactide)‐co‐glycolide] at the air–water interface

The understanding of the simultaneous transport and chain‐scission phenomena involved in the hydrolysis of bulk‐degrading polymers requires the experimental separation of chain cleavage and water diffusion. The hydrolytic chain cleavage of poly(rac‐lactide) rac‐(PLA) and poly[(rac‐lactide)‐co‐glycolide] (PLGA) is analysed on the basis of monolayer degradation experiments combined with an improved data reduction procedure. Different, partly contradictory models of the hydrolytic degradation and erosion mechanism of PLA and PLGA, namely random chain scission and chain‐end scission, are discussed in the literature. The instantaneous linear area reduction observed for the polymer Langmuir films indicates a chain‐end scission mechanism. As monolayers of end‐capped and non‐end‐capped polymers degrade with exactly the same rate, the observed differences in the degradation kinetics of bulk samples do clearly result from differences in the water penetration into these polymers. A pronounced ‘auto‐inhibition’ effect is observed for the polymers degraded at initially high pH of the aqueous subphase in the absence of buffers. Copyright © 2007 John Wiley & Sons, Ltd.     

Thermosensitive polylactide‐glycolide delivery systems for treatment of narcotic addictions

Environmental switches may be fabricated for the controlled release of pharmaceutical drug using a thermally responsive polymer with the intrinsic chemical and physical nature of stimuli‐sensitive smart materials. Particularly, much attention has been paid to the biomedical applications of poly(N‐isopropyl acrylamide) (PNIPAAm) because of its unique reversible transition at a specific lower critical solution temperature (LCST).Thermally sensitive block copolymers, poly(N‐isopropyl acrylamide‐b‐poly(L ‐lactide‐co‐glycolide) (PNIPAAm‐b‐PLGA), and polyethylene glycol‐poly (lactide‐co‐glycolide) (PEG‐PLGA) triblock copolymers with different compositions and length of PLGA block were synthesized via ring‐opening polymerization of lactide and glycolide in the presence of OH‐terminated PNIPAAm or PEG. The composition and structure of the polymer were determined by NMR and FTIR. The effect of important factors, such as ionic strength, pH, and polymer concentration on the phase transition behavior of temperature‐sensitive polymers, were investigated by cloud point measurements. The resulting thermosensitive polymers were used for the entrapment of a narcotic antagonist drug, naltrexone, as the model drug. The loading efficiency and drug release behavior of naltrexone‐loaded hydrogels were investigated. The naltrexone loaded thermosensitive polymers were able to sustain the release of naltrexone for different periods of time, depending on the polymer composition, and concentration. In vitro release studies showed that these thermosensitive polymers are able to deliver naltrexone in biologically active forms at a controlled rate for 3–8 weeks. Copyright © 2009 John Wiley & Sons, Ltd.     

Preparation of insulin-loaded PLA/PLGA microcapsules by a novel membrane emulsification method and its release in vitro

Uniform-sized biodegradable PLA/PLGA microcapsules loading recombinant human insulin (rhI) were successfully prepared by combining a Shirasu Porous Glass (SPG) membrane emulsification technique and a double emulsion-evaporation method. An aqueous phase containing rhI was used as the inner water phase (w1), and PLA/PLGA and Arlacel 83 were dissolved in a mixture solvent of dichloromethane (DCM) and toluene, which was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w1/o primary emulsion. The primary emulsion was permeated through the uniform pores of a SPG membrane into an outer water phase by the pressure of nitrogen gas to form the uniform w1/o/w2 droplets. The solid polymer microcapsules were obtained by simply evaporating solvent from droplets. Various factors of the preparation process influencing the drug encapsulation efficiency and the drug cumulative release were investigated systemically. The results indicated that the drug encapsulation efficiency and the cumulative release were affected by the PLA/PLGA ratio, NaCl concentration in outer water phase, the inner water phase volume, rhI-loading amount, pH-value in outer water phase and the size of microcapsules. By optimizing the preparation process, the drug encapsulation efficiency was high up to 91.82%. The unique advantage of preparing drug-loaded microcapsules by membrane emulsification technique is that the size of microcapsules can be controlled accurately, and thus the drug cumulative release profile can be adjusted just by changing the size of microcapsules. Moreover, much higher encapsulation efficiency can be obtained when compared with the conventional mechanical stirring method.