A highly beneficial Rose Bengal intradermal delivery system has been developed.

Rose Bengal is formulated in transfersomes loaded into trilayer microneedle array.

Transfersomes into dissolving microneedles assist the melanoma surgical 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.

Rose Bengal

Water-soluble drug

Transfersome

Microneedle

Melanoma

Intradermal delivery

active pharmaceutical ingredient

percentage drug content

dynamic light scattering

percentage height reduction

phase analysis light scattering

Rose Bengal loaded trilayer dissolving microneedles

Rose Bengal transfersomes loaded trilayer dissolving microneedles

Rose Bengal loaded transfersomes

trilayer dissolving microneedles

transmission electron microscopy

© 2022 The Author(s). Published by Elsevier B.V.