title: In vitro and in vivo study of thymosin alpha1 biodegradable in situ forming poly(lactide-co-glycolide) implants.
abstract: The purpose of this study was to develop poly(lactide-co-glycolide) (PLGA) based in situ forming implants (ISFI) for controlled release of thymosin alpha 1 (Talpha1). The ISFI was prepared by dissolving PLGA in N-methyl-2-pyrrolidone (NMP) or mixtures of NMP and triacetin. Talpha1 microparticles, prepared by spray-freeze drying method with chitosan or bovine serum albumin as a protectant, were suspended in PLGA solutions. The effects of Talpha1 pre-encapsulation, PLGA molecular weight, PLGA concentration and organic solvents composition on the in vivo Talpha1 release were evaluated by subcutaneously injecting Talpha1-loaded ISFI into Sprague-Dawley Rats. The pharmacological efficacy of Talpha1-loaded ISFI was examined using immunosuppressive BALB/c mice induced by cyclophosphamide. The ISFI composed of Talpha1 pre-encapsulated with chitosan, higher molecule-weight PLGA at higher concentration and more triacetin showed a lower initial release and a longer sustained release period. The optimal prescription of our study showed a low initial release of 29.3% (24 h), followed by a slow and continuous drug release up to 28 d in vivo. An in vitro release device was designed to mimic the in vivo release of Talpha1, and good correlation was observed between the in vitro and in vivo releases, with the linear correlation coefficient of 0.9899. Talpha1-loaded ISFI showed low cytotoxicity as tested by CCK-8 assay. Talpha1-loaded ISFI significantly increased the thymic index and spleen index of immunosuppressive mice. These results suggest that the ISFI is a suitable system for controlled release of Talpha1.
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Liu
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Guichen
authors.initials: G
authors.lastname: Zhou
authors.forename: Shaobo
authors.initials: S
authors.lastname: Xie
authors.forename: Hao
authors.initials: H
authors.lastname: Zou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yu
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D002417:Cattle; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005612:Freeze Drying; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055616:Microtechnology; D008970:Molecular Weight; D010316:Particle Size; D011098:Polyglactin 910; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents; D000077596:Thymalfasin; D013947:Thymosin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004337:Drug Carriers; D012997:Solvents; D011098:Polyglactin 910; D013947:Thymosin; D000077596:Thymalfasin