Sun Sang-Wook, Jeong Young-Il, Kim Sung-Ho
College of Pharmacy, Chosun University, Gwangju 501-759, Korea.
Arch Pharm Res. 2003 Jun;26(6):504-10. doi: 10.1007/BF02976871.
The aim of this study is to prepare biodegradable microspheres without the use of surfactants or emulsifiers for a novel sustained delivery carriers of protein drugs. A poly(epsilon-caprolactoney poly(ethylene glycol)/poly(epsilon-caprolactone) (CEC) triblock copolymer was synthesized by the ring-opening of epsilon-caprolactone with dihydroxy poly (ethylene glycol) to prepare surfactant-free microspheres. When dichloromethane (DCM) or ethyl formate (EF) was used as a solvent, the formation of microspheres did not occur. Although the microspheres could be formed prior to lyophilization under certain conditions, the morphology of microspheres was not maintained during the filtration and lyophilization process. Surfactant-free microspheres were only formed when ethyl acetate (EA) was used as the organic solvent and showed good spherical microspheres although the surfaces appeared irregular. The content of the protein in the microsphere was lower than expected, probably because of the presence of water channels and pores. The protein release kinetics showed a burst release until 2 days and after that sustained release pattern was showed. Therefore, these observations indicated that the formation of microsphere without the use of surfactant is feasible, and, this the improved process, the protein is readily incorporated in the microsphere.
本研究的目的是制备用于蛋白质药物新型缓释载体的、不使用表面活性剂或乳化剂的可生物降解微球。通过用二羟基聚乙二醇使ε-己内酯开环合成聚（ε-己内酯）/聚（乙二醇）/聚（ε-己内酯）（CEC）三嵌段共聚物，以制备无表面活性剂微球。当使用二氯甲烷（DCM）或甲酸乙酯（EF）作为溶剂时，未形成微球。尽管在某些条件下冻干前可形成微球，但在过滤和冻干过程中微球的形态无法保持。仅当使用乙酸乙酯（EA）作为有机溶剂时才形成无表面活性剂微球，尽管表面看起来不规则，但呈现出良好的球形微球。微球中蛋白质的含量低于预期，可能是由于存在水通道和孔隙。蛋白质释放动力学显示，在2天前呈突释，之后呈现缓释模式。因此，这些观察结果表明，不使用表面活性剂形成微球是可行的，并且在这种改进的工艺中，蛋白质易于掺入微球中。
