Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration

Abstract

Muxin Gong (2016) Liver-targeting self-assembled hyaluronic acidglycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration, Drug Delivery, 23:5, 1818-1829, DOI: 10.3109/10717544.2015 AbstractIn 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 silybinloaded 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 CCl 4 , 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.

Preparation and Characterization of Hyaluronic Acid-Polycaprolactone Copolymer Micelles for the Drug Delivery of Radioactive Iodine-131 Labeled Lipiodol

“…Comparing with other recently reported PCL-base micelles [23, 34–36], we found that HA-g-PCL copolymer encapsulated 131 I-lipiodol well and showed relatively low leakage of the micelles loaded with 131 I-lipiodol over time in vitro. On the other hand, HA-g-PCL copolymers also showed low leaking encapsulation of 131 I-lipiodol in our study, which was superior to other recently reported HA-based micelles/nanoparticles for differential drug deliveries [37–40]. Thus, HA-g-PCL copolymers and 131 I-lipiodol may be a particular suitable carrier-drug pair; for example, the HA-g-PCL copolymers are by nature a good micellar carrier for the 131 I-lipiodol while the loading of 131 I-lipiodol potentially upholds the stability of the formed micelles.…”

pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin

“…Chemical shifts corresponding to HA (2.0 and 3.3–4.7 ppm) were observed, and the characteristic peaks at 0.64–1.37 ppm were assigned to the typical protons of the GA moiety. The successful introduction of GA into HA was indicated by the presence of characteristic peaks at 0.6–1.4 ppm [ 27 , 33 ]. The degree of substitution (DS) was determined by comparing the average number of GA molecules attached per 100 HA molecules.…”

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

“…Dual pH/redox responsive and CD44 receptor targeting [355] Death receptor-5 antibody conjugate HA conjugate Targeted treatment of liver metastasis [356] Lanthanum HA-Pt Chemotherapeutic HA-Pt Chemotherapeutic agent HA-Pt to track In Vivo distribution of HA-Pt [357] Silybin HA-glycyrrhetinic acid micelles Liver targeted hepato protection [358] Trastuzumab. HA-tyramine sustained release hydrogels HA-tyramine sustained release hydrogels for trastuzumab.…”