Mussel-inspired quaternary composite hydrogels with high strength and high tissue adhesion for transdermal drug delivery: Synergistic hydrogen bonding and drug release mechanism

Low adhesion to skin remains a significant challenge for most hydrogel based transdermal drug delivery systems. Meanwhile, most of the methods to improve bio-adhesion often ignore the effect of the cohesion. Inspired by the adhesion mechanism of natural mussels and the synergistic balance theory based on cohesion and adhesion, we designed a poly (acrylamide-co-hydroxyethyl acrylate)-polydopamine-polyvinylpyrrolidone (PAHDP) quaternary composite hydrogel to enhance the cohesion and adhesion through the synergistic effect of multiple hydrogen bonds to achieve strong bio-adhesion to skin. The structure of PAHDP was characterized by FTIR, 1H NMR, SEM and TGA. The peeling adhesion force of PAHDP on porcine skin was improved by 9-fold compared with PAH hydrogel. At the same time, the adhesion force of drug-loaded PAHDP was 1.3 times that of Voltaren (R) EX. The rheological test further demonstrated that the synergistic hydrogen bonding can significantly improve the PAHDP cohesion. In addition, in vitro release, skin permeation and pharmacokinetics test of PAHDP hydrogel containing diclofenac sodium (DIC) showed that monomer dopamine (DA) could promote drug release. FTIR and molecular modeling were utilized to further demonstrate the enhanced drug release mechanism of DA. MTT assay, H&E staining and skin erythema analysis demonstrated that PAHDP was non-irritant to the skin. In conclusion, the innovatively prepared PAHDP hydrogel exhibits high skin adhesion, excellent mechanical properties, non-irritation and high drug release ability. This study also provides a simple and efficient strategy and theoretical basis for the preparation of high adhesion and high drug release hydrogels for transdermal drug delivery system.