Abstract
Targeting hepatic stellate cells (HSCs) can improve the therapeutic efficacy of medicines used to treat hepatic fibrosis. The present work aimed to study the feasibility of homing devices with vitamin A(VA) chemically attached for delivering betulin(Bt)specifically to HSCs. The manufacture and characterisation of VA modified poly (ethylene glycol) -poly (lactide-co-glycolide) block copolymer micelles loaded with Bt (Bt/ VAPPMs) and their potential therapeutic benefits in vitro and in vivo are described in this paper. Bt/VAPPMs were made in a nearly spherical core-shell configuration with diameters under 200nm.In vitro release study showed that Bt/VAPPMs exhibited steady and continuous release for over 168 hours. Bt/VAPPMs had good biocompatibility at the cellular level, according to the safety evaluation, and elicited no inflammatory response in mice. More importantly, as uptake behavior studied in cells and bioimaging experiments in vivo, Bt/VAPPMs exhibited an instinctive liver- targeting capability to focus on activated HSCs. Efficacy tests revealed that administering Bt/VAPPMs effectively inhibits collagen I expression in LX-2 cells in vitro, and this effect was also seen in a mouse model of liver fibrosis. Overall, results demonstrated that Bt/VAPPMs is a promising drug delivery system that possesses specific HSCs targeting ability for treating hepatic fibrosis.
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