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Int. J. Mol. Sci. 2016, 17(4), 364; doi:10.3390/ijms17040364

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

School of Bioscience and Technology, Weifang Medical University, Wei Fang 261053, Shandong, China
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Academic Editor: Már Másson
Received: 19 January 2016 / Revised: 28 February 2016 / Accepted: 7 March 2016 / Published: 30 March 2016
(This article belongs to the Special Issue Drug Delivery and Antimicrobial Agents)
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Abstract

The tumor targetability and stimulus responsivity of drug delivery systems are crucial in cancer diagnosis and treatment. In this study, hepatoma-targeting mixed micelles composed of a hyaluronic acid–glycyrrhetinic acid conjugate and a hyaluronic acid-l-histidine conjugate (HA–GA/HA–His) were prepared through ultrasonic dispersion. The formation and characterization of the mixed micelles were confirmed via 1H-NMR, particle size, and ζ potential measurements. The in vitro cellular uptake of the micelles was evaluated using human liver carcinoma (HepG2) cells. The antitumor effect of doxorubicin (DOX)-loaded micelles was investigated in vitro and in vivo. Results indicated that the DOX-loaded HA–GA/HA–His micelles showed a pH-dependent controlled release and were remarkably absorbed by HepG2 cells. Compared with free DOX, the DOX-loaded HA–GA/HA–His micelles showed a higher cytotoxicity to HepG2 cells. Moreover, the micelles effectively inhibited tumor growth in H22 cell-bearing mice. These results suggest that the HA–GA/HA–His mixed micelles are a good candidate for drug delivery in the prevention and treatment of hepatocarcinoma. View Full-Text
Keywords: hepatoma-targeting; glycyrrhetinic acid; hyaluronic acid; micelle hepatoma-targeting; glycyrrhetinic acid; hyaluronic acid; micelle
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Wu, J.-L.; Tian, G.-X.; Yu, W.-J.; Jia, G.-T.; Sun, T.-Y.; Gao, Z.-Q. pH-Responsive Hyaluronic Acid-Based Mixed Micelles for the Hepatoma-Targeting Delivery of Doxorubicin. Int. J. Mol. Sci. 2016, 17, 364.

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