Macro-to-nano dynamic hydrogels in sustained transdermal therapy of diffuse ocular surface malignancies

Conjunctival melanoma (CοΜ) is of high malignancy that diffusely impacts the ocular surface, which is challenging to surgically remove and pose a life-threatening risk. As one of the most suitable treatment options, drug dropping drugs to the eye surface, however, is limited in its clinical application for CoM treatment due to low drug utilization. Using BRAF/MEK inhibitors (BRAF/MEKi) as model drugs, this study proposes a long-lasting eyedrop based on BRAF/MEK dual-targeted liposome-doped dynamic hydrogels with drugs (B/MLDDHs), which can overcome the tear flushing to succeed in effective ocular surface drug delivery. B/MLDDHs encapsulate drugs within lipid bilayers, enhancing drug bioavailability and biocompatibility. The aldehyde dextran and protonated chitosan-based injectable hydrogel system facilitates drug retention on the ocular surface exerting a sustained liposome release, which significantly enhances the drug bioavailability. In therapeutics, this study demonstrates significantly enhanced <i>in vivo</i> therapeutic effect on orthotopic mouse model of CoM. Given their ability to fulfill permeable and long-term release of hydrophobic drugs, B/MLDDHs may serve as a promising platform for non-invasive delivery of various drug molecules, thereby improving therapeutic outcomes for CoM.