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Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies.
Zhang, Ting; Qin, Xian-Yan; Cao, Xi; Li, Wen-Hao; Gong, Tao; Zhang, Zhi-Rong.
Afiliação
  • Zhang T; Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
  • Qin XY; Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, China.
  • Cao X; Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
  • Li WH; Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
  • Gong T; Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
  • Zhang ZR; Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China. gongtaoy@126.com.
Acta Pharmacol Sin ; 40(4): 514-521, 2019 Apr.
Article em En | MEDLINE | ID: mdl-30002492
Thymopentin (TP5) is an effective immunomodulatory agent for autoimmune disease that has been used clinically 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 compliance. In the present study, we developed a TP5-loaded, phospholipid-based phase separation gel (PPSG) to achieve sustained drug release profile and long-lasting 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 sustained and controlled drug release property. Most importantly, in cyclophosphamide-induced 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 immunoregulatory effect was comparable to that produced by repeated injection of TP5 solution (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 manufacture process, good biocompatibility and long-lasting immunomodulatory efficacy, which could greatly improve patient compliance.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipídeos / Timopentina / Células Endoteliais da Veia Umbilical Humana / Fatores Imunológicos Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfolipídeos / Timopentina / Células Endoteliais da Veia Umbilical Humana / Fatores Imunológicos Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article