CONICET | Buscador de Institutos y Recursos Humanos

The aim of this work was to obtain a Vismodegib-loaded nanoformulation for topical treatment of skin precancerous lesions. Vismodegib (Vis) is a new generation drug, recently approved by the FDA for the treatment of basal cell carcinoma, with several secondary effects. Encapsulation into ultradeformable liposomes (UL) could be useful to reduce the side effects by specific-site delivery. UL were selected because are capable to penetrate the stratum corneum (SC) of the human skin. UL were prepared with Soy Phosphatidylcholine, Sodium Cholate and Vismodegib by rotary evaporation. Vesicles were extruded and non-encapsulated Vismodegib was removed by molecular exclusion chromatography. Size and stability in the time of UL-Vis were determined by DLS, zeta potential and Turbiscan Lab® Expert analysis. Lamellarity was corroborated by TEM. The interaction drug-lipid was assessed by DSC and Merocyanine 540 probe. Drug-lipid ratio and encapsulation efficiency were determined. A test of deformability was performed to study the elastic properties. Ex vivo penetration studies were performed on a Saarbrücken Penetration Model device with human skin explants. Penetration profile was quantified in the SC after tape stripping. Intact skin and transversal sections of 20 µm were studied by CLSM. A unimodal population of UL-Vis with a mean size of 116.40 ± 2.09 nm and zeta potential of -19.30 ± 0.76 mV, without significant variation up to 30 days, was obtained. There were not observed events of coalescence, sedimentation or creaming, thus the formulation was stable in time. Vismodegib was retained in the liposomal membrane and modified its deformability and temperature and enthalpy of lipid transition. UL-Vis was capable to penetrate the SC of intact human skin. These results allow to continue in the design of a future topical therapy, maximizing the availability of Vismodegib in the area of the lesion and reducing systemic side effects.