Vitamin A - modified Betulin polymer micelles with hepatic targeting capability for hepatic fibrosis protection

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(V_A) chemically attached for delivering betulin(Bt)specifically to HSCs. The manufacture and characterisation of V_A modified poly (ethylene glycol) -poly (lactide-co-glycolide) block copolymer micelles loaded with Bt (Bt/ V_APPMs) and their potential therapeutic benefits in vitro and in vivo are described in this paper. Bt/V_APPMs were made in a nearly spherical core-shell configuration with diameters under 200nm.In vitro release study showed that Bt/V_APPMs exhibited steady and continuous release for over 168 hours. Bt/V_APPMs 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/V_APPMs exhibited an instinctive liver- targeting capability to focus on activated HSCs. Efficacy tests revealed that administering Bt/V_APPMs 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/V_APPMs is a promising drug delivery system that possesses specific HSCs targeting ability for treating hepatic fibrosis.