Comparative Evaluation of Covalent Conjugates and Non-Covalent Complexes of Inulin-Based Polymeric Systems for Doxorubicin Delivery

Abstract

Polymer-based drug delivery systems offer a promising approach to overcome the limitations of conventional anticancer chemotherapy. In this study, two inulin-derived systems for doxorubicin delivery were developed using covalent conjugation with dialdehyde inulin and non-covalent complexation with sodium carboxymethyl inulin. Physicochemical characterization confirmed successful polymer modification and drug incorporation. The covalent conjugates exhibited higher structural stability and a more compact morphology than the corresponding non-covalent complexes. Under acidic conditions, the conjugates showed sustained drug release, reaching approximately 82% after 72 h, consistent with the acid-sensitive hydrolysis of Schiff base linkages. In vitro studies using HeLa cells demonstrated that the conjugates retained anticancer activity comparable to free doxorubicin despite lower drug loading. Acute toxicity studies further revealed a marked reduction in systemic toxicity, with no mortality observed at doses up to 6000 mg kg-1 (median lethal dose (LD50) > 6000 mg kg-1). Overall, the findings indicate that covalent immobilization of doxorubicin onto dialdehyde inulin is a promising strategy for developing safer polymer-based drug delivery systems and supports the potential of inulin-derived conjugates for further anticancer applications.