Natural cationic polymer-derived injectable hydrogels for targeted chemotherapy

Injectable hydrogels have the potential to revolutionize therapeutics. Therapeutic hydrogels exhibit distinctive physicochemical properties, including flexible porous structure, binding affinity for biological fluids, porous structural configuration, higher water content, high flexibility, biodegradability, and biocompatibility. These technologies have had tremendous clinical implications, specifically for the site-specific and sustained delivery of chemotherapeutic drugs. Drug-encapsulated injectable hydrogels showcase significant superiority over conventional therapeutics, such as minimized adverse effects, enhanced therapeutic efficacy, augmented pharmacological profile, and superior patient compliance. Conventional approaches mainly include intravenous chemotherapy, which can potentially cause adverse effects such as myelosuppression, nephro- or hepatic dysfunction, and neurotoxicity. The injectable hydrogel is a potent approach to overcome these impediments by releasing the chemotherapeutic drugs at specific tumor sites after topical administration. Moreover, the therapeutic efficiency of cancer immunotherapy is majorly dependent upon the tumor microenvironment, which can be targeted with chemotherapeutic drug-loaded injectable hydrogels for improved cancer therapy. In addition, natural cationic polymers such as chitosan, cyclodextrins, gelatin, cellulose, dextran, and others have received substantial attention from investigators in drug delivery due to their easy obtainability, high encapsulation efficiency, improved bioavailability, sustained drug release properties, biodegradability, and biocompatibility. This review summarizes the mainstream approaches for synthesizing injectable hydrogels and the biological properties of different natural cationic polymers. We have also focused on the notable studies of cationic polymers used definitively to fabricate hydrogel-mediated systems for anticancer drug delivery. Further, the therapeutic approaches, molecular insights, pharmacological actions, and clinical significance have been discussed.