In vitro Evaluation of Lysozyme-loaded Microspheres in Thermosensitive Methylcellulose-based Hydrogel  

作　　者：林莹 孙佳丽 蒋国强 昝佳 丁富新 

机构地区：[1]Department of Chemical Engineering, Tsinghua University, Beijing 100084, China

出　　处：《Chinese Journal of Chemical Engineering》2007年第4期566-572,共7页中国化学工程学报（英文版）

基　　金：Supported by the National Natural Science Foundation of China （No.20576057） and Fundamental Research Foundation of Tsinghua University （JCqn2005033）.

摘　　要：Long-terrn injectable microspheres have some inherent disadvantages such as migration of microspheres from the originalsite an.d the burst effect. In order to avoid these problems, microsphere-loaded thermosensitive, hydrogel system was designed and expected to achieve a zero-order release Of biomolecular drugs in relativehigh initial drug loadings. Lysozyme, an antibacterial protein usually used to reduce prosthetic valve endocarditis,was selected as the model drug. Poly （DL-lactide-co-glycolide） （PLGA） microspheres, prepared by solvent evaporation method, were employee to encapsulate lysozyme and dispersed into thermosensitive pre-gel solution containing methylcellulose （MC）, polyethylene glycol （PEG）, sodium citrate （SC）, and sodium alginate （SA）. The mixture could act asadrug reservoir by.performing sol-gel transition rapidly if the temperature was raised from roomtemperature to 37℃. The in vitro release results showed that the burst effect was avoided due to strengthening ofdiffusion resistance in the gel. The formulation was able.to deliver lysozy.me for over.30 daysin a nearly zero-order release profile with a rate of 32.8μg.d^-1 which exhibits its remarkable potential for effective aoolication in long-term drug delivery.Long-term injectable microspheres have some inherent disadvantages such as migration of micro- spheres from the original site and the burst effect.In order to avoid these problems,microsphere-loaded thermosen- sitive hydrogel system was designed and expected to achieve a zero-order release of biomolecular drugs in relative high initial drug loadings.Lysozyme,an antibacterial protein usually used to reduce prosthetic valve endocarditis, was selected as the model drug.Poly(DL-lactide-co-glycolide)(PLGA)microspheres,prepared by solvent evapo- ration method,were employed to encapsulate lysozyme and dispersed into thermosensitive pre-gel solution con- taining methylcellulose(MC),polyethylene glycol(PEG),sodium citrate(SC),and sodium alginate(SA).The mix- ture could act as a drug reservoir by performing sol-gel transition rapidly if the temperature was raised from room temperature to 37℃.The in vitro release results showed that the burst effect was avoided due to strengthening of diffusion resistance in the gel.The formulation was able to deliver lysozyme for over 30 days in a nearly zero-order release profile with a rate of 32.8μg.d -1 which exhibits its remarkable potential for effective application in long-term drug delivery.

关 键 词：MICROSPHERE thermosensitive hydrogel drug release LYSOZYME METHYLCELLULOSE 

分 类 号：TQ41[化学工程]