Mechanism insight on drug skin delivery from polyurethane hydrogels: Roles of molecular mobility and intermolecular interaction.

Though polyurethane (PU) hydrogel had great potential in topical drug delivery system, drug skin delivery behavior from hydrogel and the underlying molecular mechanism were still unclear. In this study, PU and Carbomer (CP as control) hydrogels were prepared with lidocaine (LID) and ofloxacin (OFX) as model drugs. In vitro skin permeation and tissue distribution study were conducted to evaluate the drug delivery behaviors. The underlying molecular mechanisms were characterized by drug release with octanol as release medium, rheological study, ATR-FTIR, NMR, and molecular simulation. The results showed that the skin permeation amount of LID-PU (45.50 ± 7.12 μg) was lower than LID-CP (45.50 ± 7.12 μg). And the LID diffusion coefficient of PU (26.21 μg/h0.5) was also lower than CP (31.30 μg/h0.5), which attributed to H-bonding between LID (-CONH) and PU (-NHCOO). However, the OFX-PU showed a higher skin permeation amount (10.06 ± 1.29 μg) than OFX-CP (5.28 ± 1.39 μg). And the OFX-PU also showed a higher diffusion coefficient (30.0 μg/h0.5) than OFX-CP (21.37 μg/h0.5), which was caused by increased mobility of hydrogel when interaction action site was C-O-C in PU. In conclusion, drug skin delivery behavior from PU hydrogel was controlled by molecular mobility and intermolecular interaction, which clarified the influence of the functional group of PU hydrogel on drug skin delivery behavior and broadened our understanding of PU hydrogel application in topical drug delivery system.