Biophysical characterization of Vismodegib-loaded ultradeformable liposomes: drug-membrane interaction

ALONSO, S. DEL V.; LLOVERA, R.; CALIENNI, M. NATALIA; MONTANARI, JORGE

Varadero

Workshop; IUBMB-IUPAB Advanced School and Workshop; 2018

IUPAB

Vismodegib is a new generation drug recently approved by the FDA, used to treat adults with basal cell carcinoma, but it has several secondary effects when is administered parenterally. Therefore, the encapsulation of Vismodegib into a nano-drug delivery system enables to reduce the side effects and to achieve a specific-site delivery. Ultradeformable liposomes (UDL) were selected as nanocarrier because they can penetrate the limiting barrier of the human skin: the stratum corneum, and release their content into the viable epidermis.UDL were prepared with Soy Phosphatidylcholine, Sodium Cholate and Vismodegib (51.6:17:3, molar ratio). Vesicles were extruded, passing through a membrane with pores of 100 nm, to reduce in size and lamellarity.The formulation was characterized in size and the presence of instability phenomena over time were determined by Dynamic Light Scattering, ζ potential, Turbiscan Lab® Expert analysis, and Transmission Electron Microscopy. Drug-lipid ratio and encapsulation efficiency were also determined. The interaction between Vismodegib and the liposomal membrane was studied thoroughly by DSC, FT-IR, and by Laurdan and Merocyanine 540 probes. Finally, the effect of the encapsulation of Vismodegib into the liposomal membrane on its elastic properties was assessed, determining deformability parameters of the Vismodegib-loaded UDL in comparison to empty UDL and conventional (non-flexible) liposomes.