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A 7%w/w ectoine formula, from natural source, is formulated to reduce melanomagenesis, enhance penetration by 3D printed microneedles (MNs), with specified length, diameter and tip to ensure painless effect. Ectoine gel formulations were prepared using Carbopol 940 and Pluronic (F127). The effect of the polymers on pH, viscosity, spreadability, and the  in vitro ,  ex vivo  release profiles was obtained. The physiochemical investigation showed uniform gel formulations. The formulations’  in vitro  and  ex vivo  drug release displayed a controllable drug release pattern, reaching 63.7–96% and 73–94.7% after 24 h. The permeation study of the  in vitro  and  ex vivo  release revealed that the drug release from gels followed diffusion mechanism. The selected formula was used, 3D printed MN array was applied to treat melanoma. Male rats were used for induction of melanoma using 0.5% of 7,12-dimethylbenz[a]anthracene three times weekly for 12 weeks, histopathology was applied to ensure development of carcinoma then rats were treated using the selected formula. Following treatment for continuous 6 weeks, histopathology showed a change in anatomy of skin, which started to return to its normal structure. The anti-melanogenesis activity of optimum formula of ectoine gel, enhanced by 3D printed MN, was found to be effective in reducing the severity of skin cancer reinforcing the efficacy of the promising treatment.

Ectoine gel transdermal formulation as a novel therapeutic approach in melanoma using 3D printed microneedles