Probing the mechanism of release process from metal coordination-based acrylic pressure-sensitive adhesives: Synergistic effect of coordination and hydrogen bonding for controlled drug release.

Hydrogen bonding, ionic interactions, and dipole-dipole interactions have been extensively studied to control drug release from patches. However, metal coordination bonding has not been fully explored for the control of transdermal drug release. In this study, metal coordination-based acrylic pressure-sensitive adhesives (PSAs) were designed and synthesized in order to systemically elucidate the effect of metal coordination on drug release from acrylic PSAs. Ketoprofen (KET) and donepezil (DNP) were selected as model drugs. Results showed that the burst release rate of KET was controlled by N-[tris(hydroxymethyl)methyl]acrylamide (NAT) and Fe3+, while the DNP release rate had no significant changes. It was found that the PSA-drug interaction, rather than the molecular mobility of PSA, played a dominant role in the controlled release process of KET. The hydrogen bond interaction between NAT and KET controlled the release process, while the coordination bond interaction between Fe3+ and KET further slowed down the release of KET. In conclusion, it was found that the controlled release of KET was achieved by the synergistic effect of coordination bonding and hydrogen bonding, which opens up a facile but powerful avenue for the design of brand-new controlled release systems and new opportunities for their application in transdermal drug delivery.