Dual drug delivery system based on high toughness PAM/Gel hydrogel blended with chitosan microsphere

Abstract

In this study, chitosan (CS) microspheres incorporated with polyacrylamide (PAM)/gelatin (Gel) hydrogel were fabricated using sodium tripolyphosphate (TPP) as cross-linking agent. The addition of TPP based on the optimal CS microsphere concentration, significantly enhanced hydrogel mechanical properties. Specifically, the composite hydrogel exhibited an elongation at break and tensile strength of 900% and 268.26 kPa, respectively, compared to 135.56 kPa and 419.03% for the PAM/Gel hydrogel. Furthermore, compressive strength at 70% strain was 2.1 times greater than that of the unmodified hydrogel. The composite hydrogel's network structure, rich in non-covalent bonds such as electrostatic interactions, hydrogen bonds, π-π interactions, and metal coordination bonds, exhibits excellent self-healing and self-adhesion properties. Following 18 hours of self-healing at room temperature, 92.2% of the original tensile strength was recovered. Additionally, the PAM/Gel/CS hydrogels exhibited powerful self-adhesive ability. Even after five bonding cycles to porcine skin, a substantial adhesion strength of 36.43 kPa was maintained, corresponding to 54% of the initial strength. Finally, in vitro studies revealed a controlled and sustained release profile for both 5-Fluorouracil (5-FU) and Tetracycline hydrochloride (TH) from the composite hydrogel. The observed increase in water uptake under acidic conditions of PAM and chitosan further accelerate drug release. Therefore, this dual-drug delivery hydrogel system, exhibiting excellent mechanical properties, suggests promise for pH-responsive therapeutic applications.