Nano-formulation for topical treatment of precancerous lesions: skin penetration, in vitro, and in vivo toxicological evaluation

TEKINAY, AYSE BEGUM; ALONSO, SILVIA DEL VALLE; PRIETO, MARIA JIMENA; MONTANARI, JORGE; PAOLINO, DONATELLA; MONTANARI, JORGE; FRESTA, MASSIMO; CALIENNI, MARIA NATALIA; FRESTA, MASSIMO; TEMPRANA, CARLOS FACUNDO; TEKINAY, AYSE BEGUM; TEMPRANA, CARLOS FACUNDO; ALONSO, SILVIA DEL VALLE; PRIETO, MARIA JIMENA; PAOLINO, DONATELLA; CALIENNI, MARIA NATALIA

Drug Delivery and Translational Research

Springer

Lugar: New York; Año: 2017 vol. 8 p. 496 - 514

2190-393X

With the aim of improving the topical delivery of theantineoplastic drug 5-fluorouracil (5FU), it was loaded into ultradeformable liposomescomposed of soy phosphatidylcholine and sodium cholate (UDL-5FU). The liposomepopulations had a mean size of 70 nm without significant changes in 56 days,and the ultradeformable formulations were up to 324-fold more elastic than conventionalliposomes. The interaction between 5FU and the liposomal membrane was studiedby three methods, and also release profile was obtained. UDL-5FU did penetratethe stratum corneum of human skin. At in vitro experiments, theformulation was more toxic on a human melanoma-derived than on a humankeratinocyte-derived cell line. Cells captured liposomes by metabolicallyactive processes. In vivo toxicity experiments were carried out in zebrafish (Danio rerio) larvae by studying the swimming activity,morphological changes, and alterations in the heart rate after incubation.UDL-5FU was more toxic than free 5FU. Therefore, this nano-formulation could beuseful for topical application in deep skin precancerous lesions with advantagesover current treatments. This is the first work that assessed the induction ofapoptosis, skin penetration in a Saarbrücken penetration model, and thetoxicological effects in vivo of an ultradeformable 5FU-loaded formulation.