Octyl succinic anhydride-modified chitosan/oxidized sodium alginate Schiff base hydrogel loaded with terbinafine hydrochloride: pH-responsive, self-repairing, antifungal properties.

The application of hydrogels to drug delivery limited by the difficulty of encapsulating hydrophobic drugs; therefore, the development of novel composite hydrogels for the delivery of hydrophobic drugs is urgently needed. In this study, terbinafine hydrochloride/hydroxypropyl-β-cyclodextrin inclusion complexes (TFH/HP-β-CD ICs) were added to a Schiff base hydrogel matrix containing octenyl succinic anhydride-modified chitosan (OSA-CS) and sodium alginate (OIA) to prepare a TFH composite hydrogel (TFH GEL). The results revealed that the solubility of TFH in water within TFH/HP-β-CD IC reached 32.13 mg/mL. The TFH GEL successfully encapsulated the IC without any drug leakage and exhibited excellent acid pH responsiveness. Moreover, the hydrogels were mechanically stable, self-healing, and injectable. Haemocompatibility and cytotoxicity tests confirmed the excellent biocompatibility of the TFH GEL. Importantly, TFH GEL effectively inhibited Microsporum canis growth in vitro and in vivo. In summary, a novel composite hydrogel was developed by combining a modified natural polymer hydrogel with a complexing agent to deliver the hydrophobic antifungal drug TFH, this study provides a new strategy for treating fungal skin infections.