The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo

CALIENNI, MARIA NATALIA; MAZA VEGA, DANIELA; TEMPRANA, C. FACUNDO; IZQUIERDO, MARÍA CECILIA; YBARRA, DAVID E.; BERNABEU, EZEQUIEL; MORETTON, MARCELA; ALVIRA, FERNANDO C.; CHIAPPETTA, DIEGO; ALONSO, SILVIA DEL VALLE; PRIETO, MARÍA JIMENA; MONTANARI, JORGE

Pharmaceutics

MDPI

Año: 2021 vol. 13

Abstract: Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its dailyoral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities.Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems werethe most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformableliposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can beloaded in several delivery systems for topical application. These findings may be also useful for theconsideration of topical delivery of other drugs with a low water solubility