In vitro and in vivo study of thymosin alpha1 biodegradable in situ forming poly(lactide-co-glycolide) implants

International Journal of Pharmaceutics
Qingfeng LiuYanqiang Zhong

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...Continue Reading

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Jul 26, 2013·Therapeutic Delivery·Luis Solorio, Agata A Exner
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