Controlled release of protein drugs from newly developed amphiphilic polymer-based microparticles composed of nanopcarticles
Controlled release of protein drugs from newly developed amphiphilic polymer-based microparticles composed of nanopcarticles
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DOI：
10.1016/j.jconrel.2009.09.024
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发表时间：
2010-02-25
影响因子：
10.8
通讯作者：
Ida, Nobuo
中科院分区：
文献类型：
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作者：
Kakizawa, Yoshinori;Nishio, Reiji;Ida, Nobuo
开发了一种可生物降解的微粒的新型配方，以持续释放肽和蛋白质药物。微粒是通过蛋白质纳米颗粒通过油中的（w/o）乳液 - 脊髓化和随后的水中固体（S/O/W）乳液溶剂蒸发形成的。将两亲性共聚物用作乳液和微粒基质中的乳化剂。在所研究的各种共聚物中，根据封装效率和体外释放概况，选择了聚（乳酸 - 乙二醇）晶状葡萄糖（DEX-G-PLGA）作为最佳候选者人类生长激素（HGH）的显着初始爆发。 HGH的释放速率可通过更改DEX-G-PLGA的组成来控制。使用正常小鼠的体内释放研究表明，将HGH的血浆浓度保持1周而没有明显的初始爆发。通过测量降低小鼠的IGF-1浓度和体重来证实HGH生物学活性通过持续释放的增强。这些结果表明，新开发的微粒具有持续释放生物药物的高潜力。 （c）2009 Elsevier B.V.保留所有权利。
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 1 week 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. (C) 2009 Elsevier B.V. All rights reserved.