Nanokaolin-reinforced chitosan/poly(vinyl alcohol) hydrogels as transdermal patches with superior anti-swelling, adhesion, and drug release.

Abstract

Hydrogel patches are promising platforms for transdermal drug delivery; however, their clinical applicability is often limited by excessive swelling, which compromises adhesion stability and may provoke tissue inflammation. Herein, we report the incorporation of kaolin nanosheets (NKLS) and kaolin nanoscrolls (NKLC) into chitosan/poly(vinyl alcohol) (CS/PVA)-based hydrogels to concurrently suppress swelling, augment interfacial interactions, and reconstruct drug storage microdomains. Compared to the pristine CS/PVA control, the CS/NKLC/PVA patch demonstrated a 139.91% higher BET surface area and a significantly lower swelling ratio of 18.74% in PBS (pH 6.0), which corresponds to a 63.59% reduction. Both CS/NKLS/PVA and CS/NKLC/PVA patches exhibited excellent mechanical properties. Compared with the pristine CS/PVA control, their adhesive stress was increased by 26.48% and 16.55%, respectively, and both patches maintained stable adhesion after 10 peeling-adhesion cycles. Drug release rates reached 82.37% and 86.78% for the respective patches, with Fickian diffusion identified as the dominant release mechanism. The incorporation of nanokaolin resulted in a denser crosslinked network that restricted chain relaxation and subsequent swelling. Additionally, NKLS introduced additional interfaces and adsorption sites, increasing the tortuosity of drug diffusion pathways, while the hollow tubular structure of NKLC provided enhanced drug storage space and diffusion channels. Furthermore, both CS/NKLS/PVA and CS/NKLC/PVA patches exhibited excellent antibacterial activity against Staphylococcus aureus and Escherichia coli. In conclusion, these nanokaolin-modified hydrogel patches demonstrate substantial potential for transdermal drug delivery and wound dressing applications.