title: Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration.
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 Cmax 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.
authors.affiliation: a Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University , Beijing , P. R. China and.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Han
authors.affiliation: a Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University , Beijing , P. R. China and.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University , Beijing , P. R. China and.
authors.forename: Manyuan
authors.initials: M
authors.lastname: Wang
authors.affiliation: a Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University , Beijing , P. R. China and.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: a Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University , Beijing , P. R. China and.
authors.forename: Yongsong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: a Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University , Beijing , P. R. China and.
authors.forename: Rui
authors.initials: R
authors.lastname: He
authors.affiliation: a Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University , Beijing , P. R. China and.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guan
authors.affiliation: b Beijing YouAn Hospital, Capital Medical University , Beijing , P. R. China.
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Yue
authors.affiliation: a Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University , Beijing , P. R. China and.
authors.forename: Muxin
authors.initials: M
authors.lastname: Gong
mesh_terms: D000284:Administration, Oral; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods; D006034:Glycyrrhetinic Acid / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008823:Micelles; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008823:Micelles; D012838:Silymarin; D000077385:Silybin; D006820:Hyaluronic Acid; D006034:Glycyrrhetinic Acid
keywords: Amphiphilic conjugate; glycyrrhetinic acid; hyaluronic acid; oral bioavailability; targeting drug delivery