Effect of Excipients on Stability and Structure of rhCuZn-SOD Encapsulated in PLGA Microspheres  

作　　者：LIU Ling 1,2 ,GE Yu 1 and YUAN Qin-sheng 1 1. State Key Laboratory of Bioreactor Engineering and Institute of Biochemistry,East China University of Science and Technology,Shanghai 200237,P. R. China 2. Public Health School,Nanjing Medical University,Nanjing 210029,P. R. China 

出　　处：《Chemical Research in Chinese Universities》2004年第3期323-327,共5页高等学校化学研究（英文版）

摘　　要：When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic solvent and a polymer may cause the denaturation of the protein. In this study,we investigated the enzymatic activity change and the effect of the excipients on the stability of recombinant human Cu,Zn-superoxide dismutase(rhCu,Zn-SOD) during the emulsification. The specific activity recovery was found to be concentration dependent and the excipients involved such as PEG 600 and Tween 20,and trehalose were shown to increase the stability of rhCu,Zn-SOD. The protein structural integrity within the microspheres was analyzed by FTIR. The structure of rhCu,Zn-SOD within PLGA microspheres containing trehalose was found to be similar to that of the native solid state,whereas the protein encapsulated during the preparation in the absence of any excipient changed due to the possible hydrophobic interaction with the polymer. The results suggest that a rational stability strategy for protein to be encapsulated into microspheres should aim at different processes.When a protein is encapsulated into poly( DL -lactide-co-glycolide)(PLGA) microspheres by means of the double-emulsion method,the harsh microspheres formation process including ultrasonification,exposure to an organic solvent and a polymer may cause the denaturation of the protein. In this study,we investigated the enzymatic activity change and the effect of the excipients on the stability of recombinant human Cu,Zn-superoxide dismutase(rhCu,Zn-SOD) during the emulsification. The specific activity recovery was found to be concentration dependent and the excipients involved such as PEG 600 and Tween 20,and trehalose were shown to increase the stability of rhCu,Zn-SOD. The protein structural integrity within the microspheres was analyzed by FTIR. The structure of rhCu,Zn-SOD within PLGA microspheres containing trehalose was found to be similar to that of the native solid state,whereas the protein encapsulated during the preparation in the absence of any excipient changed due to the possible hydrophobic interaction with the polymer. The results suggest that a rational stability strategy for protein to be encapsulated into microspheres should aim at different processes.

关 键 词：Poly( DL -lactide-co-glycolide)(PLGA) microsphere Recombinant human Cu Zn-superoxide dismutase(rhCu Zn-SOD) Fourier transform infrared(FTIR) spectroscopy Protein stability EXCIPIENT 

分 类 号：O629[理学—有机化学]