A transdermal drug delivery system based on hydrogel patches was explored, leveraging their sustainable release properties for hydrophilic drugs. Despite these advantages, conventional hydrogels often lacked proper adhesion to the skin. In response, we designed skin-adhesive hydrogels using polyacrylamide/polydopamine (PMA/PDA) formulations, with polydopamine derived from mussel shells known for its excellent adhesive properties. Comparative analysis revealed that PMA/PDA hydrogels exhibited a higher swelling ratio than those without PDA. These hydrogels were incorporated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the hydrophobic component vitamin E. The resulting hydrogel system demonstrated sustained release of vitamin E under physiological conditions, presenting a promising avenue for transdermal delivery of vitamin E.