Next Article in Journal
Identification of Serum Peptidome Signatures of Non-Small Cell Lung Cancer
Next Article in Special Issue
Design and Application of Antimicrobial Peptide Conjugates
Previous Article in Journal
Thymoquinone Modulates Blood Coagulation in Vitro via Its Effects on Inflammatory and Coagulation Pathways
Previous Article in Special Issue
Biomaterials with Antibacterial and Osteoinductive Properties to Repair Infected Bone Defects
Article Menu
Issue 4 (April) cover image

Export Article

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
Authors to whom correspondence should be addressed.
Academic Editor: Már Másson
Int. J. Mol. Sci. 2016, 17(4), 364;
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)
PDF [3115 KB, uploaded 30 March 2016]


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

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top