Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies  

作　　者：Ting Zhang Xian-yan Qin Xi Cao Wen-hao Li Tao Gong Zhi-rong Zhang 

机构地区：[1]Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China [2]Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China

出　　处：《Acta Pharmacologica Sinica》2019年第4期514-521,共8页中国药理学报（英文版）

基　　金：National Natural Science Foundation of China (81690261 and 81673359).

摘　　要：Thymope ntin (TP5) is an effective immuno modulatory age nt for autoimm une disease that has bee n used clin ically for decades. However, its application is greatly limited by its extremely short half-life in vivo, poor membrane permeability and extensive metabolism in gastrointestinal tract, resulting in repeated injection and poor patient complianee. In the present study, we developed a TP5-loaded, phospholipid-based phase separation gel (PPSG) to achieve sustained drug release profile and longlasting therapeutic effects. We firstly demonstrated the physiochemical characteristics of PPSG before and after phase transition by examining the viscosity and morphology change caused by the phase transition. Moreover, the PPSG exerted a low cytotoxicity in L929 cells and HUVECs, suggesting the biocompatibility of PPSG. A month-long drug release profile of TP5 PPSG was observed both in vitro and in vivo, revealing its sustai ned and con trolled drug release property. Most importa ntly, in cyclophosphamide-i nduced immunosuppressive rats, a single dose of TP5 PPSG (15 mg/kg, sc) injected could normalize their T-SOD levels and CD4+/CD8+ ratio;such an immuno regulatory effect was comparable to that produced by repeated injectio n of TP5 soluti on (0.6 mg/kg per day, sc) for 14 consecutive days. Thus, TP5 PPSG has a great potential for sustained delivery of TP5 in clinical use because of its simple man ufacture process, good biocompatibility and long-lasti ng immuno modulatory efficacy, which could greatly improve pati ent complia nee.

关 键 词：THYMOPENTIN phospholipid-based PHASE separation gel (PPSG) PHASE transition SUSTAINED drug release pharmacokinetics immunoregulatory effect 

分 类 号：R[医药卫生]