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Open AccessArticle

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
Int. J. Mol. Sci. 2016, 17(4), 364; https://doi.org/10.3390/ijms17040364
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)
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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MDPI and ACS Style

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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