New Frontiers Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
J Control Release. 2010 Feb 25;142(1):8-13. doi: 10.1016/j.jconrel.2009.09.024. Epub 2009 Oct 3.
A novel formulation of biodegradable microparticles was developed for the sustained release of peptide and protein drugs. The microparticles were formed by the aggregation of protein nanoparticles through water-in-oil (W/O) emulsion-lyophilization and subsequent solid-in-oil-in-water (S/O/W) emulsion-solvent evaporation. Amphiphilic copolymers were used as an emulsifier in the W/O emulsion and matrix of the microparticles. Among the various copolymers investigated, poly(lactide-co-glycolide)-grafted dextran (Dex-g-PLGA) was chosen as the best candidate on the basis of the encapsulation efficiency and in vitro release profile, the near zero-order release without a significant initial burst, of human growth hormone (hGH). The release rate of hGH was controllable by changing the composition of Dex-g-PLGA. The in vivo release studies using normal mice revealed that the plasma concentration of hGH was maintained for 1week without a significant initial burst. The enhancement of biological activity of hGH by sustained release was confirmed by measuring the IGF-1 concentration and body weight of hypophysectomized mice. These results suggest the high potential of the newly developed microparticles for the sustained release of biopharmaceuticals.
一种新型的可生物降解微球制剂被开发用于肽类和蛋白质类药物的缓释。微球通过油包水（W/O）乳液-冷冻干燥和随后的固-油-水（S/O/W）乳液-溶剂蒸发使蛋白质纳米颗粒聚集形成。两亲性共聚物在 W/O 乳液和微球基质中用作乳化剂。在所研究的各种共聚物中，基于包封效率和体外释放曲线，选择聚（乳酸-共-乙醇酸）接枝葡聚糖（Dex-g-PLGA）作为最佳候选物，其具有接近零级释放而没有明显的初始突释，用于人生长激素（hGH）。通过改变 Dex-g-PLGA 的组成可以控制 hGH 的释放速率。使用正常小鼠进行的体内释放研究表明，hGH 的血浆浓度在没有明显初始突释的情况下维持 1 周。通过测量去垂体小鼠的 IGF-1 浓度和体重来确认 hGH 通过持续释放提高生物活性。这些结果表明，新开发的微球在生物制药的缓释方面具有很高的潜力。
