Trilayer dissolving polymeric microneedle array loading Rose Bengal transfersomes as a novel adjuvant in early-stage cutaneous melanoma management

Melanoma remains a global concern, but current therapies present critical limitations pointing out the urgent
need for novel strategies. Among these, the cutaneous delivery of drugs selectively damaging cancer cells is
highly attractive. Rose Bengal (RB) is a dye exhibiting selective cytotoxicity towards melanoma, but the high
water solubility and low permeability hinder its therapeutic potential. We previously developed RB-loaded
transfersomes (RBTF) to mediate the RB dermal delivery; however, a platform efficiently delivering RBTF in
the deepest strata is essential for a successful therapeutic activity. In this regard, dissolving microneedles release
the encapsulated cargo up to the dermis, painlessly piercing the outmost skin layers. Therefore, herein we
developed and characterised a trilayer dissolving microneedle array (RBTF-TDMNs) loading RBTF to maximise
RBTF intradermal delivery in melanoma management. RBTF-TDMNs were proven strong enough to pierce
excised porcine skin and rapidly dissolve and deposit RBTF intradermally while maintaining their physicochemical properties. Also, 3D visualisation of the system itself and while penetrating the skin was performed by
multi-photon microscopy. Finally, a dermatokinetic study showed that RBTF-TDMNs offered unique delivery
efficiency advantages compared to RBTF dispersion and free drug-loaded TDMNs. The proposed RBTF-TDMNs
represent a valuable potential adjuvant tool for the topical management of melanoma.