Injectable, self-healing chimeric catechol-Fe(III) hydrogel for localized combination cancer therapy

Abstract

Conventional intravenous or oral administration of a combination of chemotherapeutics displays poor bioavailability and induces undesirable systemic toxicity. Therefore, localized delivery of such chemotherapeutic combinations using polymeric hydrogels is expected to help in enhancing drug efficacy and reducing systemic toxicity. In this manuscript, we have utilized a chitosan-catechol based hydrogel (CAT-Gel) assembled through catechol-Fe(III) coordinative interactions for localized combination therapy in murine lung and breast cancer models. CAT-Gel offers a unique blend of material properties such as injectability and self-healing along with useful biological attributes like their noncytotoxic and nonhemolytic nature. The amphipathic nature of this hydrogel enabled us to incorporate a recipe of hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic docetaxel (DTX) anticancer drugs. Rheology studies confirmed the self-healing nature of this chimeric hydrogel even after drug loading. CAT-Gel was retained for more than 40 days in mice upon subcutaneous injection. The sequential and sustained release of the entrapped DOX and DTX from the hydrogel resulted in synergistic therapeutic effect with increased median survival against murine lung and breast cancer models. Therefore, CAT-Gel provides a new coordinatively assembled biocompatible scaffold for localized delivery of chemotherapeutic drugs.