Injectable hyaluronic acid-tyramine hydrogels incorporating interferon-α2a for liver cancer therapy.

Abstract

We report an injectable hydrogel system that incorporates interferon-α2a (IFN-α2a) for liver cancer therapy. IFN-α2a was incorporated in hydrogels composed of hyaluronic acid-tyramine (HA-Tyr) conjugates through the oxidative coupling of Tyr moieties with hydrogen peroxide (H2O2) and horseradish peroxidase (HRP). IFN-α2a-incorporated HA-Tyr hydrogels of varying stiffness were formed by changing the H2O2 concentration. The incorporation of IFN-α2a did not affect the rheological properties of the hydrogels. The activity of IFN-α2a was furthermore well-maintained in the hydrogels with lower stiffness. Through the caspase-3/7 pathway in vitro, IFN-α2a released from HA-Tyr hydrogels inhibited the proliferation of liver cancer cells and induced apoptosis. In the study of the pharmacokinetics, a higher concentration of IFN-α2a was shown in the plasma of mice treated with IFN-α2a-incorporated hydrogels after 4h post injection, with a much higher amount of IFN-α2a delivered at the tumor tissue comparing to that of injecting an IFN-α2a solution. The tumor regression study revealed that IFN-α2a-incorporated HA-Tyr hydrogels effectively inhibited tumor growth, while the injection of an IFN-α2a solution did not demonstrate antitumor efficacy. Histological studies confirmed that tumor tissues in mice treated with IFN-α2a-incorporated HA-Tyr hydrogels showed lower cell density, with more apoptotic and less proliferating cells compared with tissues treated with an IFN-α2a solution. In addition, the IFN-α2a-incorporated hydrogel treatment greatly inhibited the angiogenesis of tumor tissues.

• Authors: Keming Xu, Fan Lee, Shu Jun Gao, Joo Eun Chung, Hirohisa Yano, Motoichi Kurisawa
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 166 Issue 3 Pg. 203-10 (Mar 28 2013) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 23328125 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Hydrogels
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Hyaluronic Acid
• Tyramine

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Carriers (chemical synthesis, chemistry)
• Female
• Humans
• Hyaluronic Acid (chemistry)
• Hydrogels (chemistry)
• Injections, Subcutaneous
• Interferon alpha-2
• Interferon-alpha (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Liver Neoplasms (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Recombinant Proteins (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Solubility
• Tyramine (chemistry)
• Xenograft Model Antitumor Assays