Optimization and evaluation of curcumin-loaded zein microneedles for potential treatment of melanoma

Treatment of melanoma is challenging due to limited bioavailability of chemotherapeutic drugs, side effects, and poor patient compliance with conventional intravenous administration. We evaluated the potential of synthesizing zein microneedles (ZMNs) using curcumin (Cur) as an anticancer model compound as a non-invasive approach for the local treatment of melanoma. A QbD approach was employed to create ZMNs with optimal mechanical strength and membrane penetrability, using zein as the matrix and PVP as a plasticizer at a concentration of 50% (w/v) and 20% (w/v), respectively. ZMNs loaded with Cur at 0.5% drug loading (Cur-ZMNs) demonstrated suitable mechanical properties, desirable membrane insertion, and sustained Cur release in vitro up to 76.17% over 24 h. Ex vivo permeation studies with excised porcine skin showed significantly higher permeation of Cur from Cur-ZMNs (59.75 %) when compared to free Cur (11%). Cur-ZMNs efficiently killed A375 melanoma cells and reduced cell viability by 44%, which was comparable to that of free Cur. The membrane damage of melanoma cells, measured by lactate dehydrogenase (LDH) assay, further supported the cytotoxic effect of Cur-ZMNs against treated cells, while showing no toxic effect against normal fibroblasts, indicating the potential of prepared Cur-ZMNs for effective treatment of melanoma.