To achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activity of the optimal ethosomal preparation when applied topically to chemically induced skin cancer in mice. We utilized a statistical Box–Behnken experimental design and applied three variables at three levels: lecithin concentration, cholesterol concentration and a mixture of ethanol and isopropyl alcohol concentrations. All formulations were prepared to calculate the entrapment efficiency %, zeta potential, size of the vesicles and drug release % after 1, 2, 4, 8 and 24 h. The size of the vesicles for the formulations was between 124 ± 14.2 nm and 560 ± 127 nm, while the entrapment efficiency was between 97.8 ± 0.23% and 99.4 ± 0.24%, and the drug release % after 8 h was between 38 ± 0.82% and 66 ± 0.52%. All formulations were introduced into the Box–Behnken software, which selected three formulations; then, one was assigned as an optimal formula. The in vivo antitumor activity of metformin-loaded ethosomal gel on skin cancer was greater than the antitumor activity of the gel preparation containing free metformin. Lower lecithin, high ethanol and isopropyl alcohol and moderate cholesterol contents improved the permeation rate. Overall, we can conclude that metformin-loaded ethosomes are a promising remedy for treating skin cancers, and more studies are warranted to approve this activity in other animal models of skin cancers.

The purpose of drug administration through the skin is to treat skin disorders on a topical level or to deliver drugs to the systemic circulation via transdermal absorption due to the variability in peak plasma concentration following oral and parenteral delivery. Ethosomes lipid-based nanovesicles with improved softness, deformability, and elasticity, are the most investigated vesicular system. Ethanol, cholesterol, and lecithin are used to prepare ethosomes. The loose hair follicles and Stratum Corneum (SC) percutaneous route allowed the ethosomes to permeate the epidermis. During percutaneous penetration, the vesicles were released into the superficial layer of the skin, allowing the therapeutic substances to penetrate while the phospholipids remained in the upper epidermis. Skin physiology, drug physicochemical factors, and the delivery system determine the frequency and degree of drug absorption through the skin. The present transdermal dosage forms, such as patches, ointments, and creams, are associated with several limitations. One of the most unpleasant side effects of transdermal patches is skin irritation, caused by their occlusive properties, which block sweat ducts, preventing water drainage from the skin surface. Other disadvantages include difficulties applying to curved surfaces, pain while peeling away, and a lack of aesthetic appeal

Background/Objectives: An observed increase in fungal infection incidence over the past two decades underscores the limitations of conventional topical treatments for deep infections, primarily due to the skin’s stratum corneum barrier. This has driven the development of advanced topical preparations. This study evaluated the encapsulation of oxiconazole utilizing novasomes to enhance its topical delivery. Methods: Oxiconazole-loaded novasomes were synthesized by the ethanol injection technique and subsequently characterized using key physicochemical parameters, including encapsulation efficiency (EE%), vesicle size (VS), zeta potential (ZP), polydispersity index (PDI), and percentage drug release (DR%). The optimized formulation underwent comprehensive evaluation employing Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and transmission electron microscopy (TEM). Moreover, its activity was evaluated through in vitro penetration studies and in vivo assessments. Results: R9 was identified as the optimal candidate, demonstrating an encapsulation efficiency of 94.63 ± 1.60%, a vesicle size of 174 ± 1.15 nm, a zeta potential of −46.5 ± 1.61 mV, a polydispersity index of 0.184 ± 0.01, and a drug release rate of 51 ± 0.50% within 8 h. This optimal formula achieved 94 ± 1.75% permeation of oxiconazole within 24 h. FTIR examination affirmed the interaction of oxiconazole and the excipients, while DSC analysis verified the thermal durability of oxiconazole. In vivo histopathological examination demonstrated the superior efficacy of the optimal formula in treating Candida albicans infection. Conclusions: Novasomes emerge as a promising and efficacious system for oxiconazole encapsulation, holding significant potential for the effective and prolonged management of topical fungal infections.