Folate-conjugated methoxy poly(ethylene glycol)/poly(epsilon-caprolactone) amphiphilic block copolymeric micelles for tumor-targeted drug delivery.

Amphiphilic block copolymers composed of methoxy poly(ethylene glycol) (MPEG) and poly(epsilon-caprolactone) (PCL) were synthesized and then conjugated with folic acid to produce a folate-receptor-targeted drug carrier for tumor-specific drug delivery. Folate-conjugated MPEG/PCL micelles containing the anticancer drug paclitaxel were prepared by micelle formation in aqueous medium. The size of the folate-conjugated MPEG/PCL micelles formed was about 50-130 nm, depending on the molecular weight of block copolymers, and was maintained at less than 150 nm even after loading with paclitaxel. The in vitro release profile of the paclitaxel from the MPEG/PCL micelles exhibited no initial burst release and showed sustained release. Paclitaxel-loaded folate-conjugated MPEG/PCL micelles (PFOL50) exhibited much higher cytotoxicity for cancer cells, such as MCF-7 and HeLa cells, than MPEG/PCL micelles without the folate group (PMEP50). Confocal image analysis revealed that fluorescent paclitaxel-loaded PFOL50 micelles were endocytosed into MCF-7 cells through the interaction with overexpressed folate receptors on the surface of the cancer cells.     

Understanding drug release from poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) gels.

Experimental and mathematical studies were performed to understand the release mechanism of small molecular weight compounds from poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) polymer gels (trademarked Pluronic by BASF Corp.) of various concentrations. Studies of the diffusion coefficient of solutes in the polymer gels were performed using a novel technique to predict movement of drugs within the gel as release occurs. Studies were also performed to determine the diffusion coefficient of water in the polymer gel, as it is this parameter that controls the dissolution rate of the polymer, and in turn, the drug release rate. A model was formulated and solved numerically to determine the controlling release mechanism. By parameter modification, this algorithm for determining the overall mass of drug released from a drug loaded gel can be used for a number of drugs and for a wide range of initial polymer concentrations. Drug release data were obtained with a novel experimental setup and were used to verify the accuracy of the overall solution of the model. The results of the model indicate that although the rate of polymer dissolution ultimately controls the drug release, about 5% of the release is due to diffusion at the gel/liquid interface, giving rise to a slightly non-linear release. It was also found that agitation speed greatly affects the dissolution rates of these polymer gels.     

In vitro release of the mTOR inhibitor rapamycin from poly(ethylene glycol)-b-poly(epsilon-caprolactone) micelles.

An injectable formulation of rapamycin was prepared using amphiphilic block co-polymer micelles of poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-PCL). Drug-loaded PEG-PCL micelles were prepared by a co-solvent extraction technique. Resulting PEG-PCL micelles were less than 100 nm in diameter and contained rapamycin at 7% to 10% weight and >1 mg/mL. PEG-PCL micelles released rapamycin over several days, t50% 31 h, with no burst release; however, physiological concentrations of serum albumin increased the release rate 3-fold. Alpha-tocopherol, vitamin E, was co-incorporated into PEG-PCL micelles and increased the efficiency of rapamycin encapsulation. The addition of alpha-tocopherol also slowed the release of rapamycin from PEG-PCL micelles in the presence of serum albumin, t50% 39 h.     

Lipophilic prodrugs of Hsp90 inhibitor geldanamycin for nanoencapsulation in poly(ethylene glycol)-b-poly(epsilon-caprolactone) micelles.

A solvent and Cremephor free formulation of the anticancer chemotherapeutic geldanamycin was prepared using amphiphilic block co-polymer micelles of poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-b-PCL). Although geldanamycin was not solubilized by PEG-b-PCL micelles, fatty acid prodrugs of geldanamycin were encapsulated in PEG-b-PCL micelles by a co-solvent extraction technique. Resulting PEG-b-PCL micelles were <120 nm in diameter and solubilized >20% w/w geldanamycin prodrugs increasing aqueous solubility to >2 mg/mL. PEG-b-PCL micelles released the geldanamycin prodrugs over several days, t(1/2) 2.2 to 9.6 days. The free prodrugs hydrolyzed rapidly, t(1/2)<6 h, into the geldanamycin analogue 17-beta-hydroxyethylamino-17-demethoxygeldanamycin, which has high activity against MCF-7 breast cancer cells, IC(50) 240 nM.     

Micellar carriers based on block copolymers of poly(epsilon-caprolactone) and poly(ethylene glycol) for doxorubicin delivery.

Diblock copolymers of poly(epsilon-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5-24.7 kDa) in the copolymer composition. Hemolytic studies showed that free DOX caused 11% hemolysis at 200 microg ml(-1), while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37 degrees C demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells.     

Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic)/poly(epsilon-caprolactone) (PCL) amphiphilic block copolymeric nanospheres. I. Preparation and characterization.

Amphiphilic block copolymers based on PEO-PPO-PEO block copolymer (Pluronic) and poly(epsilon-caprolactone) were synthesized by bulk polymerization. The structural analysis of Pluronic/PCL block copolymer was carried out using FT-IR, 1H NMR, GPC, WAXD, DSC and TGA measurements. To prepare copolymeric nanospheres with a micellar structure, Pluronic/PCL amphiphilic block copolymers were dialyzed against water. The size and size distribution of Pluronic/PCL block copolymeric nanospheres were examined by dynamic light scattering measurement. They showed an average diameter of 116 to 196 nm depending on the type of copolymer. All the nanosphere samples exhibited a narrow size distribution. The critical micelle concentrations of Pluronic/PCL amphiphilic block copolymers determined by fluorescence spectroscopy were lower than that of common low molecular weight surfactants. We confirmed the formation of stable copolymeric nanospheres through the solution behavior of amphiphilic block copolymer in selective solvents.     

Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)/poly(epsilon-caprolactone) (PCL) amphiphilic block copolymeric nanospheres. II. Thermo-responsive drug release behaviors.

Amphiphilic block copolymers composed of relatively hydrophilic PEO-PPO-PEO block copolymer (Pluronic) and poly (epsilon-caprolactone) with hydrophobic character were synthesized by ring-opening polymerization of epsilon-caprolactone in the presence of PEO-PPO-PEO block copolymer using stannous octoate as a catalyst. Pluronic/PCL block copolymeric nanospheres with core-shell structure were prepared by dialysis method. They showed the average diameter of 116-196 nm depending on the type of copolymer. All the nanosphere samples exhibited a narrow size distribution. The critical micelle concentrations of Pluronic/PCL amphiphilic block copolymers determined by fluorescence spectroscopy were lower than that of the common low molecular weight surfactant. Their core-shell structure was confirmed by 1H NMR spectroscopy. Pluronic/PCL block copolymeric nanospheres exhibited the reversible change of size depending on the temperature. Release behaviors of indomethacin from Pluronic/PCL block copolymeric nanospheres also showed temperature dependence and a sustained release pattern. In addition, cytotoxicity test using an MTT assay method revealed that these indomethacin-loaded Pluronic/PCL nanospheres could remarkably reduce the cell damage compared with the unloaded free indomethacin.     

Tumor pH-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-histidine)

Polymeric micelles were constructed from poly(l-lactic acid) (PLA; M_n 3K)-b-poly(ethylene glycol) (PEG; M_n 2K)-b-poly(l-histidine) (polyHis; M_n 5K) as a tumor pH-specific anticancer drug carrier. Micelles (particle diameter: ∼ 80 nm; critical micelle concentration (CMC): 2 μg/ml) formed by dialysis of the polymer solution in dimethylsulfoxide (DMSO) against pH 8.0 aqueous solution, are assumed to have a flower-like assembly of PLA and polyHis blocks in the core and PEG block as the shell. The pH-sensitivity of the micelles originates from the deformation of the micellar core due to the ionization of polyHis at a slightly acidic pH. However, the co-presence of pH-insensitive lipophilic PLA block in the core prevented disintegration of the micelles and caused swelling/aggregation. A fluorescence probe study showed that the polarity of pyrene retained in the micelles increased as pH was decreased from 7.4 to 6.6, indicating a change to a more hydrophilic environment in the micelles. Considering that the size increased up to 580 nm at pH 6.6 from 80 nm at pH 7.4 and that the transmittance of micellar solution increased with decreasing pH, the micelles were not dissociated but rather swollen/aggregated. Interestingly, the subsequent decline of pyrene polarity below pH 6.6 suggested re-self-assembly of the block copolymers, most likely forming a PLA block core while polyHis block relocation to the surface. Consequently, these pH-dependent physical changes of the PLA-b-PEG-b-polyHis micelles provide a mechanism for triggered drug release from the micelles triggered by the small change in pH (pH 7.2–6.5).     

Poly(ethylene oxide)-modified poly(beta-amino ester) nanoparticles as a pH-sensitive biodegradable system for paclitaxel delivery.

The main objective of this study was to develop and characterize a pH-sensitive biodegradable polymeric nanoparticulate system for tumor-selective paclitaxel delivery. A representative hydrophobic poly(beta-amino ester) (poly-1) was synthesized by conjugate addition of 4,4'-trimethyldipiperidine with 1,4-butanediol diacrylate. Poly-1 (M(n) 10,000 daltons) nanoparticles were prepared by the controlled solvent displacement method in an ethanol-water system in the presence of Pluronic) F-108, a poly(ethylene oxide) (PEO)-containing non-ionic surfactant. Control and PEO-modified nanoparticles were characterized by Coulter counter, scanning electron microscopy (SEM), zeta potential measurements, and electron spectroscopy for chemical analysis (ESCA). Polymer degradation studies were performed in phosphate-buffered saline (PBS, pH 7.4) at 37 degrees C. Paclitaxel loading capacities and efficiencies were determined and release studies were performed in Tween)-80 (0.1%, w/v)-containing PBS at 37 degrees C. Control and PEO-modified nanoparticles, labeled with rhodamine-123, were incubated with BT-20 cells to examine the uptake and cellular distribution as a function of time. PEO-modified nanoparticles with an average size of 100-150 nm and a positive surface charge of 37.0 mV were prepared. SEM analysis showed distinct smooth, spherical particles. The ether (-C-O-) peak of the C(1s) envelope in ESCA confirmed the surface presence of PEO chains. Polymer biodegradation studies showed that almost 85% of the starting material degraded after 6 days. The maximum paclitaxel loading efficiency attained was 97% at 1.0% (w/w) of the drug. Paclitaxel release studies showed that approximately 10% was released in the first 24 h, 80% after 3 days, and the entire content was released in approximately 5 days. After 1 h of incubation, a large fraction of the administered control and PEO-modified poly-1 nanoparticles was internalized in BT-20 cells. Results of this study demonstrate that PEO-modified poly-1 nanoparticles could provide increased therapeutic benefit by delivering the encapsulated drug to solid tumors.     

Micelles self-assembled from poly(ethylene oxide)-block-poly(N-hexyl stearate L-aspartamide) by a solvent evaporation method: effect on the solubilization and haemolytic activity of amphotericin B.

The goal of this study was to assess a solvent evaporation method for the encapsulation of amphotericin B (AmB) in poly(ethylene oxide)-block-poly(N-hexyl stearate L-aspartamide) (PEO-b-PHSA) micelles. By the solvent evaporation method, PEO-b-PHSA self-assembled into small spherical micelles with a high AmB content based on transmission electron microscopy, size exclusion chromatography and absorption spectroscopy. The encapsulation of AmB was slightly better than an earlier method based on dialysis. Importantly, AmB in PEO-b-PHSA micelles encapsulated by the solvent evaporation method was non-haemolytic at 15 microg/ml, whereas AmB in PEO-b-PHSA micelles encapsulated by the dialysis method caused 50% haemolysis at the level of 3.8 microg/ml, and AmB itself caused 100% haemolysis at 1.0 microg/ml. Thus, PEO-b-PHSA micelles could effectively encapsulate AmB, increase the overall water solubility of AmB and reduce the toxicity of the membrane-acting drug, particularly by a solvent evaporation method.     

Evaluation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) gels as a release vehicle for percutaneous fentanyl.

The primary objective of this study was to investigate the feasibility of PEO-PPO-PEO copolymer gel as a release vehicle for percutaneous administration of fentanyl in vitro and in vivo. A cellulose membrane and nude mouse skin with series concentrations of PEO-PPO-PEO block copolymers were used to examine the sustained-release pattern and permeation of fentanyl. The in vivo percutaneous absorption was examined using rabbits to evaluate the preliminary pharmacokinetics of fentanyl with 46% PEO-PPO-PEO copolymer formulation patches. The micelle formation ability of this block copolymer and the penetration ability of PEO-PPO-PEO copolymer over time were also studied by pyrene fluorescence probe methods and the dynamic light scattering test. At a concentration of 46% at 37 degrees C, PEO-PPO-PEO copolymers formed a gel and showed a pseudo-zero-order sustained-release profile. With increasing concentration of copolymer in the cellulose membrane transport, the apparent release flux of fentanyl (200 microgram/ml) decreased to 1. 09+/-0.19 microgram cm(-2) h(-1). Assessment of the effect of the copolymer on nude mouse skin also showed a decrease in the apparent permeability coefficient [(P(H(2)O))=2.24+/-0.47x10(-6) cm s(-1) vs. (P(46% block copolymer))=0.93+/-0.23x10(-7) cm s(-1)]. The preliminary pharmacokinetics of the fentanyl patch was shown to be in steady state within 24 h, and this was maintained for at least 72 h with an elimination half-life (t(1/2)) of 10.5+/-3.4 h. A fluorescence experiment showed polymeric micelle formation of PEO-PPO-PEO copolymers at 0.1% (w/w) within 50 nm micelle size and the PEO-PPO-PEO copolymers were able to penetrate nude mouse skin within 24 h. Thus, it appears that fentanyl preparations based on PEO-PPO-PEO copolymer gel might be practical for percutaneous delivery.     

Thermoreversible gelation of biodegradable poly(epsilon-caprolactone) and poly(ethylene glycol) multiblock copolymers in aqueous solutions.

The multiblock copolymers composed of poly(ethylene glycol)s (PEGs) and biodegradable poly(epsilon-caprolactone)s (PCLs) were synthesized through one-step condensation copolymerization with hexamethylene diisocyanate (HDI) as a coupling agent. The typical phase diagram of these multiblock copolymers in aqueous solution displayed a critical gel concentration (CGC) and an upper phase-transition temperature, which were mainly determined by the PEG/PCL block ratio, the PEG or PCL block lengths and the molecular weight. With decreasing PEG/PCL block ratio, the CGC decreased with an elevated sol-gel transition temperature on account of the enhanced hydrophobicity. The HDI/Diols ratio was used to control the molecular weight. At high molecular weights, the CGC decreased, related to the enhanced aggregation of PCL blocks and physical crosslinkage between PCL block domains due to the increased number of PCL blocks in each molecule. For the sample containing the long PCL(2000) block (M(n), 2000), the CGC dropped dramatically due to the high hydrophobicity and the poor compatibility between PCL and PEG. The dynamic phase transition process was observed by combining optical microscopy (OM) and differential scanning calorimetry (DSC) in a certain heating/cooling rate. Finally, a possible phase separation-induced gelation mechanism is suggested.     

Polycaprolactone-b-poly(ethylene oxide) copolymer micelles as a delivery vehicle for dihydrotestosterone.

Block copolymer micelles formed from copolymers of poly(caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) were investigated as a drug delivery vehicle for dihydrotestosterone (DHT). The physical parameters of the PCL-b-PEO micelle-incorporated DHT were measured, including the loading capacity of the micelles for DHT, the apparent partition coefficient of DHT between the micelles and the external medium and the kinetics of the release of DHT from the micelle solution. The MTT survival assay was used to assess the in vitro biocompatibility of PCL-b-PEO micelles in HeLa cell cultures. The biological activity of the micelle-incorporated DHT was evaluated in HeLa cells which had been co-transfected with the expression vectors for the androgen receptor and the MMTV-LUC reporter gene. The PCL-b-PEO micelles were found to have a high loading capacity for DHT and the release profile of the drug from the micelle solution was found to be a slow steady release which continued over a 1-month period. The biological activity of the micelle-incorporated DHT was found to be fully retained.     

In vivo gene delivery into ocular tissues by eye drops of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles.

The primary objective of this study was to investigate the feasibility of using PEO-PPO-PEO non-ionic copolymeric micelles as a carrier for eye-drop gene delivery of plasmid DNA with lacZ gene in vivo. Using pyrene fluorescence probe methods, zeta potential, and dynamic light scattering test (DLS), the ability of micelle formation of these block copolymers with plasmid was studied. Gene expressions were visualized by both the quality of enzymatic color reaction using X-gal staining and by the quantification of the substrate chlorophenol red galactopyranoside (CPRG) in enucleated eyes on day 2 after gene transfer. In addition, microscopy to identify the types of cell showing uptake and expression of the transferred gene was used. We found that the block polymeric micelles were formed above 0.1% (w/v) of block copolymer with a size of 160 nm and a zeta potential of -4.4 mV. After 2 days of topically delivery three times a day, the most intense gene expression was observed on days 2 and 3. Reporter expression was detected around the iris, sclera, conjunctiva, and lateral rectus muscle of rabbit eyes and also in the intraocular tissues of nude mice upon in vivo topical application for 48 h with a DNA/polymeric micelle formulation. Furthermore, after two enhancement treatments, the transport mechanisms of the block copolymeric micelles were found through endocytosis in tissues by enhancement through the tight junction pathway. Thus, efficient and stable transfer of the functional gene could be achieved with PEO-PPO-PEO polymeric micelles through topical delivery in mice and rabbits. These in vivo experiments indicate the possible potential use of block copolymers for DNA transfer.     

New segmented copolymers containing poly(epsilon-caprolactone) and etheramide segments for the controlled release of bioactive compounds.

Segmented poly(ether-ester-amide)s (PEEAs) derived from poly(epsilon-caprolactone) oligomers, sebacoyl chloride, hydrophilic diamide-diamines based on short sequences of ethylenoxy groups and containing amino acids, were used to produce matrix systems intended for the delivery of metronidazole in the periodontal pocket. PEEAs are soluble in chloroform and insoluble in water and show M(n) values in the range 8.5-18.6 kDa. The melting temperatures (53-59 degrees C) are close to that of poly(epsilon-caprolactone) (PCL) with a similar M(n). The water absorption of PEEAs is improved if compared with that of pure PCL and depends on both the length of oxyethylene sequences and the amino acid number, as well as on copolymer composition. Loaded-films containing 20% (w/w) of metronidazole were prepared by compression-molding. The release rate was diffusive in the first stage, whereas also other mechanisms, probably polymer degradation, contributed to the slower second phase. The rate of medium penetration within the film depended on PEEA hydrophilicity and crystallinity and was the main determinant governing the drug release rate. The opportunity to control effectively drug release rates by modulating the composition, and in turn the properties, of PEEAs is an attracting feature for their use in a number of drug delivery systems.     

生物可降解材料聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物与人脐静脉内皮细胞的相容性

背景:聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物膜片材料在构建组织工程支架上具有良好的应用前景,内皮细胞能否在该材料上存活和稳定生长将直接影响其作为载内皮细胞载体支架表面可降解材料的应用.目的:观察聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物与人脐静脉内皮细胞的相容性.设计;随机对照观察.单位:吉林大学第二临床医学院.材料:本实验于2006-02/10于吉林大学基础医学院病理生理教研室完成.长约20 cm脐带来自吉林大学第二医院妇产科1名正常足月分娩的新生儿,标本采集经新生儿家属知情同意,本实验经过医院伦理委员会批准.聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物膜片由中国科学院长春应用化学研究所提供.倒置显微镜及相差显微镜为日本Olympus公司产品.方法:将从脐带中分离培养的稳态生长的人脐静脉内皮细胞接种于聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物膜片上培养作为实验组,对照组为未放聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物膜片的培养皿.①以相差显微镜下观察细胞生长情况评价人脐静脉内皮细胞与聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物膜片的细胞相容性.②采用MTT法检测细胞种植后1,3,5及7 d的细胞增殖指数.主要观察指标:①人脐静脉内皮细胞与聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物膜片的细胞相容性.②细胞种植后1,3,5及7 d的细胞增殖指数.结果:①人脐静脉内皮细胞与聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物膜片的细胞相容性:相差显微镜下种植在聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物膜片上的细胞4～6 h后即开始贴壁、伸展,3 d后细胞开始呈集落样生长,生长较快,5 d后细胞集落开始融合,呈现特征性的鹅卵石样形态,经多次传代后,细胞呈长梭形或多角形,与对照组相比无明显差异.扫描电镜下观察在聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物膜片上培养15 d的人脐静脉内皮细胞嵌入膜片间隙生长,但没有连接成片铺在膜片上.②细胞增殖指数:MTT法检测结果显示实验组及对照组实验后1,3,5及7 d的细胞增殖指数差异无显著性意义(P＞0.05).结论:内皮细胞在聚乙二醇-聚乳酸-聚谷氨酸三嵌段共聚物上生长良好,两者具有良好的细胞相容性.     

Development of an injection molded poly(epsilon-caprolactone) intravaginal insert for the delivery of progesterone to cattle.

This paper reports experiments conducted to research, develop and clinically evaluate an injection molded intravaginal insert manufactured from the biodegradable polyester poly(epsilon-caprolactone). The study demonstrated that it is possible to engineer poly(epsilon-caprolactone) into a shape that is well retained, and can be used as a platform for the controlled delivery of progesterone via the vagina of cows. Field evaluation showed that the poly(epsilon-caprolactone) intravaginal inserts containing 10% (w/w) progesterone were at least as effective clinically as the commercially available CIDR intravaginal insert.     

Bioadhesive poly(methyl methacrylate) microdevices for controlled drug delivery.

Oral delivery is the preferred route of drug administration. However, the breakdown of molecules and low levels of absorption in the gastrointestinal system render the oral delivery of proteins and peptides ineffective. Bioadhesive delivery devices can be used to circumvent these problems by protecting the drug from gastrointestinal denaturation, localizing and prolonging a drug at a specific target site, and maintaining direct contact with the intestinal cells, thereby increasing the drug concentration gradient. Microfabrication technology may offer some potential advantages over conventional delivery technologies. The benefits of microfabrication include the ability to tailor the size, shape, reservoir volume, and surface characteristics of the drug delivery vehicle. In this study, bioadhesive properties were introduced to microfabricated poly(methyl methacrylate) (PMMA) microdevices by attachment of lectins, a group of proteins capable of specifically targeting cells in the gastrointestinal tract. In this process, the PMMA microdevices were chemically modified by aminolysis to yield amine-terminated surfaces. Avidin molecules were covalently bound to the surface of the particles using a hydroxysuccinimide catalyzed carbodiimide reagent and then incubated in an aqueous solution of biotinylated lectin. The lectin-modified microdevices were examined in vitro in terms of their bioadhesive characteristics.     

Novel design of microreservoir-dispersed matrices for drug delivery formulations: Regulative drug release from poly(ethylene oxide)- and poly(tetramethylene oxide)-based segmented polyurethanes

Drug release from the monolithic devices of segmented polyether-poly(urethane-urea) (PEUU)s based on both poly (tetramethylene oxide) (PTMO) and poly (ethylene oxide) (PEO) as their soft segments were thoroughly investigated in terms of the relationship between their microdomain structure and the drug release profiles. These PEUUs exhibited diverse microdomain structure depending upon the differences in the solubility parameter of constituting segments and their weight fractions in the polymers. The drug release profiles of these PEUUs were closely connected with the mode of microdomain structure composed of the PTMO, PEO, and hard segments. That is, the formation of distinct microdomains of the PTMO and hard segments dispersed in the PEO matrices allowed the definite regulation of both release rate and transport mode of drug release in the monolithic devices of highly water-swollen PEUUs. These results indicate that the design consisting of microdomains has distinct function as a drug reservoir and transport channel and is a promising way for regulating the release profile of drugs with a variation of solubility parameters from highly water swollen polymeric formulations.