Hierarchically Reinforced Gelatin/Phytic Acid Composite Sponges with Electrostatic Affinity for Long-Term Sustained Release of Cationic Drugs

Natural polymer-based sustained-release drug delivery systems are often hampered by insufficient structural stability and weak intermolecular affinities between the drug and the polymeric matrix. To overcome these limitations, herein, we engineered a covalently/non-covalently crosslinked porous gelatin sponge using a chemical crosslinker and polyanionic phytic acid (PA). PA reinforced the gelatin backbone and provided abundant electronegative phosphate groups as drug-anchoring sites, creating a high-affinity microenvironment. Using differently charged model drugs, the sponges exhibited prolonged release, with the release kinetics fitting the Higuchi model. Notably, in vitro release of cationic drugs extended beyond 200 h. These results translated into in vivo therapeutic efficacy, as validated in local anesthesia models using bupivacaine and wound repair models with polyhexamethylene biguanide. In summary, this designed porous framework offers a promising paradigm for fabricating natural polymer-based sustained-release drug delivery systems.