Dacarbazine-loaded bilayer dissolving microneedle array patch for localized delivery in cutaneous melanoma

Melanoma is a highly aggressive skin cancer that accounts for only ~ 1% of all skin cancer cases but is responsible for most skin cancer-related deaths. Despite advances in systemic therapies, localized treatment options remain limited. Dacarbazine (DCB), the only FDA-approved chemotherapeutic agent for melanoma, is administered intravenously and is associated with systemic toxicity, poor patient compliance, and nonspecific drug distribution. This study presents a bilayer dissolving microneedle array patch (dMAP) for localized, minimally invasive delivery of DCB to the skin, offering a potential alternative for treating cutaneous melanoma. The tip-casting gel formulation was optimized to ensure sharp, defect-free MAP tips with uniform drug distribution. The optimized bilayer dMAP exhibited strong mechanical properties (< 10% needle deformation) and effective insertion capability, reaching approximately 390 µm in depth within the Parafilm® M model. Ex vivo evaluations using full-thickness neonatal porcine skin demonstrated the complete dissolution of bilayer dMAP tips within 60 min and effective pore formation, as confirmed by methylene blue staining. In ex vivo setup, the bilayer dMAP formulation demonstrated 3.93-fold increase in permeability and a 3.02-fold increase in DCB deposition compared with those of the suspension. Furthermore, bilayer dMAP maintained complete drug stability over 8 days at room temperature under light-protected conditions, whereas free DCB showed approximately 7.5% degradation in aqueous media over the same duration. Therefore, bilayer dMAP provides a stable, minimally invasive, and efficient platform for localized drug delivery to the skin, highlighting its potential as a promising alternative to conventional topical formulations for the treatment of cutaneous melanoma.