Frauke Pistel K, Breitenbach A, Zange-Volland R, Kissel T
Department of Pharmaceutics and Biopharmacy, Philipps-University, Ketzerbach 63, D-35032, Marburg, Germany.
J Control Release. 2001 May 18;73(1):7-20. doi: 10.1016/s0168-3659(01)00231-0.
Brush-like branched polyesters, obtained by grafting poly(lactic-co-glycolic acid), PLGA, onto water-soluble poly(vinyl alcohol) (PVAL) backbones, were investigated regarding their utility for the microencapsulation of proteins. Poly(vinyl alcohol)-graft-poly(lactic-co-glycolic acid), PVAL-g-PLGA, offers additional degrees of freedom to manipulate properties such as e.g. molecular weight, glass transition temperature and hydrophilicity. PLGA chain length was varied at a constant molecular weight (M(w)) of the PVAL backbone and secondly M(w) of the PVAL backbone was varied keeping the PLGA chain lengths constant. The most striking feature of these polymers is their high M(w). Microencapsulation of hydrophilic macromolecules, such as bovine serum albumin, ovalbumin, cytochrome c and FITC-dextran using a w/o/w double emulsion technique was investigated. Surface morphology, particle size, encapsulation efficiencies and protein release profiles were characterized as well. Microencapsulation of model compounds was feasible at temperatures of 0-4 degrees C with yields typically in the range of 60-85% and encapsulation efficiencies of 70-90%. Both, encapsulation efficiency and initial protein release (drug burst) were strongly affected by the glass transition temperature, T(g), of the polymer in contact with water, whereas the in vitro protein release profile depended on the PVAL-g-PLGA structure and composition. In contrast to PLGA, protein release patterns were mostly continuous with lower initial drug bursts. Shorter PLGA chains increased drug release in the erosion phase, whereas initial pore diffusion was affected by the M(w) of PVAL backbone. Release profiles from 2 to 12 weeks could be attained by modification of composition and molecular weight of PVAL-g-PLGA and merit further investigations under in vivo conditions. The in vitro cytotoxicity of PVAL-g-PLGA is comparable to PLGA and therefore, this new class of biodegradable polyesters has considerable potential for parenteral drug delivery systems.
通过将聚（乳酸 - 乙醇酸共聚物）（PLGA）接枝到水溶性聚乙烯醇（PVAL）主链上获得的刷状支化聚酯，就其在蛋白质微囊化中的应用进行了研究。聚乙烯醇 - 接枝 - 聚（乳酸 - 乙醇酸共聚物）（PVAL - g - PLGA）提供了额外的自由度来操控诸如分子量、玻璃化转变温度和亲水性等性质。在PVAL主链分子量（M(w)）恒定的情况下改变PLGA链长，其次在保持PLGA链长恒定的情况下改变PVAL主链的M(w)。这些聚合物最显著的特征是它们的高M(w)。使用水包油包水双乳液技术对亲水性大分子如牛血清白蛋白、卵清蛋白、细胞色素c和FITC - 葡聚糖进行微囊化研究。还对表面形态、粒径、包封效率和蛋白质释放曲线进行了表征。在0 - 4摄氏度的温度下对模型化合物进行微囊化是可行的，产率通常在60 - 85%的范围内，包封效率为70 - 90%。包封效率和初始蛋白质释放（药物突释）都受到与水接触的聚合物的玻璃化转变温度T(g)的强烈影响，而体外蛋白质释放曲线取决于PVAL - g - PLGA的结构和组成。与PLGA相比，蛋白质释放模式大多是连续的，初始药物突释较低。较短的PLGA链增加了侵蚀阶段的药物释放，而初始孔隙扩散受PVAL主链的M(w)影响。通过改变PVAL - g - PLGA的组成和分子量可以获得2至12周的释放曲线，值得在体内条件下进一步研究。PVAL - g - PLGA的体外细胞毒性与PLGA相当，因此，这类新型可生物降解聚酯在肠胃外给药系统中具有相当大的潜力。
