Biocompatible Fe 3+ and Ca 2+ DualCross-Linked G‑Quadruplex Hydrogels as Effective Drug DeliverySystem for pH-Responsive Sustained Zero-Order Release of Doxorubicin

The ultimate aim in developing controlled drug delivery systems is to derive formulations to achieve drug release at a constant rate over a long duration. The drug release profile that follows zero-order kinetics is crucial for reduction in the drug administration frequency, reduced cytotoxicity, and improved convenience and compliance of patients. Designed drug delivery systems for achieving zero-order release are often complex, expensive, and difficult to manufacture. Herein, we demonstrate that a supramolecular hydrogel formed through the self-assembly of guanosine monophosphate (GMP) into highly ordered G-quadruplex structure and cross-linked through Fe3+ and Ca2+ ions exhibits potential for the pH-responsive controlled zero-order drug release of doxorubicin, a model chemotherapeutic drug. The fibril formation is initiated by the self-assembly of GMP into a quadruplex complex, which is cross-linked through the complexation of the phosphate groups with Fe(III) ions, resulting in a spontaneous hydrogel ...