Multilayered mucoadhesive hydrogel films based on thiolated hyaluronic acid and polyvinylalcohol for insulin delivery.

A multilayered hydrogel film system based on hyaluronic acid-cysteamine (HA-Cym) and polyvinylalcohol (PVA) was fabricated. It contained a drug-impermeable backing layer, a supporting layer preventing direct contact between the loaded drug and the backing layer, a drug-loading layer and a mucoadhesive layer. Scanning electron microscopy demonstrated the presence of the distinct layers. The composition and preparation procedure of the films influenced their mucoadhesion, swelling, in vitro release of insulin and loaded insulin stability. Vacuum drying and crosslinked PVA with glutaraldehyde might reduce mucoadhesion, and they partially decreased the bioactivity of loaded insulin. Lyophilized hydrogel film with uncrosslinked PVA as a mucoadhesive layer possessed high mucoadhesion and showed no influence on the bioactivity of loaded insulin. The application of vacuum-dried PVA-crosslinked HA-Cym/PVA hydrogel film as a drug-impermeable backing layer would provide a controllable unidirectional insulin release. Therefore, such a multilayered hydrogel film system could be a promising mucoadhesive delivery system for controlled macromolecular drug release.