Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration. (12th June 2016)

• Record Type: Journal Article
• Authors: Han, Xiaofeng; Wang, Zhe; Wang, Manyuan; Li, Jing; Xu, Yongsong; He, Rui; Guan, Hongyu; Yue, Zhujun; Gong, Muxin
• Is Part Of: Drug delivery. Volume 23:Number 5(2016:Jul.)
• Page Start: 1818
• Page End: 1829
• Publication Date: 2016-06-12
• Subjects: Amphiphilic conjugate -- glycyrrhetinic acid -- hyaluronic acid -- oral bioavailability -- targeting drug delivery; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.3109/10717544.2015.1108374
• Languages: English
• ISSNs: 1071-7544

Abstract

Abstract: In order to enhance oral bioavailability and liver targeting delivery of silybin, two amphiphilic hyaluronic acid derivatives, hyaluronic acid-deoxycholic acid (HA-adh-DOCA) and hyaluronic acid-glycyrrhetinic acid (HA-adh-GA) conjugates, were designed and synthesized. Silybin was successfully loaded in HA-adh-DOCA and HA-adh-GA micelles with high drug-loading capacities (20.3% ± 0.5% and 20.6% ± 0.6%, respectively). The silybin-loaded micelles were spherical in shape with the average size around 130 nm. In vitro release study showed that two silybin-loaded micelles displayed similar steady continued-release pattern in simulated gastrointestinal fluids and PBS. Single-pass intestinal perfusion studies indicated that silybin-loaded micelles were absorbed in the whole intestine and transported via a passive diffusion mechanism. Compared with suspension formulation, silybin-loaded HA-adh-DOCA and HA-adh-GA micelles achieved significantly higher AUC and C max level. Moreover, liver targeting drug delivery of micelles was confirmed by in vivo imaging analysis. In comparison between the two micellar formulations, HA-adh-GA micelles possessed higher targeting capacity than HA-adh-DOCA micelles, owing to the active hepatic targeting properties of glycyrrhetinic acid. In the treatment of acute liver injury induced by CCl4, silybin-loaded HA-adh-GA micelles displayed better effects over suspension control and silybin-loaded HA-adh-DOCA micelles. Overall, pharmaceutical and pharmacological indicators suggested that the HA-adh-GA conjugates can be successfully utilized for liver targeting of orally administered therapeutics.