Kim H K, Park T G
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Kusong-dong Yusong-gu, 305-701, Taejon, South Korea.
Int J Pharm. 2001 Oct 23;229(1-2):107-16. doi: 10.1016/s0378-5173(01)00852-3.
For the sustained release formulation of recombinant human growth hormone (rhGH), dissociable rhGH aggregates were microencapsulated within poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles. rhGH aggregates were first produced by adding a small volume of aqueous rhGH solution into a partially water miscible organic solvent phase (ethyl acetate, EtAc) containing PLGA. These rhGH aggregates were then microencapsulated within PLGA polymer phase by extracting EtAc into an aqueous phase pre-saturated with EtAc. Release profiles of rhGH from these microparticles were greatly affected by changing the volume of incubation medium. The released rhGH species consisted of mostly monomeric form having a correct conformation. This study reveals that sustained rhGH release could be achieved by microencapsulating reversibly dissociable protein aggregates within biodegradable polymers.
对于重组人生长激素（rhGH）的缓释制剂，可解离的rhGH聚集体被微囊化在聚（D，L-乳酸-共-乙醇酸）（PLGA）微粒中。rhGH聚集体首先通过将少量rhGH水溶液加入含有PLGA的部分与水混溶的有机溶剂相（乙酸乙酯，EtAc）中制备。然后通过将EtAc萃取到预先用EtAc饱和的水相中，将这些rhGH聚集体微囊化在PLGA聚合物相中。通过改变孵育介质的体积，rhGH从这些微粒中的释放曲线受到很大影响。释放的rhGH种类主要由具有正确构象的单体形式组成。这项研究表明，通过将可逆解离的蛋白质聚集体微囊化在可生物降解的聚合物中，可以实现rhGH的持续释放。
