Dual-Drug Loaded γ-Polyglutamic Acid Hydrogel with Hydrophilic Doxorubicin and Hydrophobic Camptothecin for Enhanced Tumor Therapy

A dual-drug-loaded γ-polyglutamic acid (γ-PGA) hydrogel was synthesized, integrating third-generation dendrimers (G3) as cross-linkers for the simultaneous encapsulation of hydrophilic doxorubicin (DOX) and hydrophobic camptothecin (CPT). This hydrogel, formed via an efficient EDC/NHS-mediated reaction, demonstrated a biocompatible, porous, and pH-responsive network. The hydrophobic core of G3 significantly enhanced CPT loading, while γ-PGA facilitated effective DOX incorporation. Controlled drug release was observed, with DOX releasing faster in acidic tumor-like environments, optimizing therapeutic impact at the tumor site. In vitro studies highlighted the hydrogel's high biocompatibility and synergistic anticancer efficacy, reducing CT26 colon cancer cell viability more effectively than single-drug systems. In vivo experiments confirmed substantial tumor suppression, prolonged survival, and the absence of systemic toxicity in murine models. These results underscore the potential of this dual-drug delivery platform as a robust, multifunctional system for cancer therapy. The biocompatibility, degradability, and tailored drug release characteristics make this hydrogel a promising candidate for clinical translation, offering a novel solution for enhancing cancer treatment efficacy while minimizing side effects.