pH-Responsive Freeze-Thawed Polyvinyl Alcohol/Chitosan Hydrogels for Topical Delivery of Anti-Inflammatory, Antioxidant, and Antibacterial Piper betle Leaf Extract Toward Wound Healing Applications

Abstract

Piper betle leaf extract (BLE) shows strong anti-inflammatory, antioxidant, and antibacterial activities. However, its application is limited due to poor water solubility, oxidative instability, and rapid clearance from the application site. To address these challenges, a crosslinker-free polyvinyl alcohol/chitosan (PVA/CS) hydrogel encapsulating BLE was developed via repeated freeze-thaw cycles. The hydrogel exhibited an interconnected porous structure, enabling stable incorporation of BLE without phase separation. As a result, the PVA/CS/BLE hydrogel achieved a high gel fraction of 89.6–94.0%, a substantial swelling capacity of 208–220%, and favorable mechanical properties, including a tensile modulus of 122.00 kPa, a tensile strength of 672.00 kPa, and an elongation at break of 242.89%. Notably, BLE release was pH-responsive, with accelerated release under simulated acute wound conditions (pH 6.5), allowing for an initial burst release of BLE to combat early-stage infections and inflammation, followed by sustained release to support wound healing. Overall, these features indicate that the PVA/CS/BLE hydrogel patch exhibits tunable structure, robust mechanical properties, and pH-responsive release behavior, highlighting its potential as a platform for delivering BLE topically in wound-healing applications.