Bae Soon Eon, Son Jun Sik, Park Kwideok, Han Dong Keun
Biomaterials Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
J Control Release. 2009 Jan 5;133(1):37-43. doi: 10.1016/j.jconrel.2008.09.006. Epub 2008 Sep 19.
Poly(lactic-co-glycolic acid) (PLGA) microsphere has been a useful tool in delivering therapeutic drugs and biologically active proteins. In this study, a covered porous PLGA microsphere was manufactured using W(1)/O/W(2) double emulsion solvent evaporation method, utilizing hydrogen peroxide as a novel porogen. An enzymatic reaction between hydrogen peroxide and catalase produced oxygen bubbles and thus many internal pores within microsphere were naturally developed. When different molar ratios between lactide and glycolide in PLGA were examined, the ratio, 50:50 showed the most organized porous microstructure. Higher molecular weight of PLGA seemed to be favorable in creating a porous structure. By testing various concentrations of hydrogen peroxide, it was found that rather concentrated one was more efficient in developing a porous network in the microspheres. The source of the skin layer that covers the whole surface of the microsphere was found to be PLGA, not polyvinyl alcohol (PVA). The residual amount of hydrogen peroxide was negligible after a thorough evaporation of PLGA microsphere. When release profiles of dexamethasone (Dex) with morphologically different microspheres such as, nonporous, covered porous, and porous, were investigated for up to 28 days in vitro, their release patterns were found to be significantly different on a temporal basis. The present work demonstrated that the covered porous PLGA microspheres could be successfully fabricated using hydrogen peroxide and that the covered skin layer on the PLGA microsphere played an important role in determining the characteristic release profiles of Dex.
聚乳酸-乙醇酸共聚物（PLGA）微球一直是递送治疗性药物和生物活性蛋白的有用工具。在本研究中，采用W(1)/O/W(2)双乳液溶剂蒸发法，以过氧化氢作为新型致孔剂，制备了包覆多孔PLGA微球。过氧化氢与过氧化氢酶之间的酶促反应产生了氧气泡，从而在微球内部自然形成了许多孔隙。当研究PLGA中丙交酯和乙交酯的不同摩尔比时，50:50的比例显示出最规整的多孔微观结构。较高分子量的PLGA似乎有利于形成多孔结构。通过测试不同浓度的过氧化氢，发现浓度较高的过氧化氢在微球中形成多孔网络方面更有效。发现覆盖微球整个表面的皮层来源是PLGA，而非聚乙烯醇（PVA）。PLGA微球彻底蒸发后，过氧化氢的残留量可忽略不计。当对形态不同的微球（如无孔、包覆多孔和多孔微球）进行地塞米松（Dex）体外释放曲线研究长达28天时，发现它们的释放模式在时间上有显著差异。目前的工作表明，使用过氧化氢可以成功制备包覆多孔PLGA微球，并且PLGA微球上的包覆皮层在确定Dex的特征释放曲线方面起着重要作用。
