Encapsulation of anti-bacterial Piper betle leaf extract in thermo-sensitive and biodegradable chitosan hydrogels: synthesis, characterization and release kinetics

Betel leaf extract (BLE) is well-known for its anti-bacterial, anti-inflammatory, and anti-oxidant activities as well as wound healing effects. For the first time, the ethanolic BLE has been successfully encapsulated into thermo-sensitive chitosan hydrogels to deliver the extract to infected wounds while preserving its biological activities. Morphologies, sol–gel transition, chemical structure, and pH of the hydrogels are comprehensively studied under the variation in the initial loading BLE concentration. Release kinetics of the hydrogels are evaluated in different environmental conditions to determine the BLE release behavior and the suitable mathematical model. The hydrogels exhibit sol–gel transition at 37.0–40.0 °C, a gelation time of 9.5–13.0 min at 37 °C, a neutral pH, and a hollow structure self-crosslinked by chitosan with both surface and internal adhesion of BLE. The BLE release from the hydrogels is affected by pH, temperature, and the BLE loading concentration and is governed by a controlled diffusion following the Korsmeyer-Peppas model. The hydrogels release 50.91–60.29% of their initial loading content and the release solutions demonstrate potent antibacterial activity against E. coli and S. aureus evidenced by the inhibition rate of 70.67–99.94%. Moreover, the chitosan hydrogels encapsulating BLE are biodegradable with a remarkably high degradability of 76.92–79.74% after 14 days of exposure to lysozyme under simulated physiological conditions. Based on the findings, the developed hydrogels are considered a potential delivery system to handle open skin wounds via local subcutaneous injection.