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

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

Drug Delivery and Translational Research

Springer

Año: 2018 p. 496 - 514

2190-393X

With the aim of improving the topical delivery of the anti-neoplastic drug 5-fluorouracil (5FU), it was loaded into ultradeformable liposomes composed of soy phosphatidylcholine and sodium cholate (UDL-5FU). The liposome populations 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 conventional liposomes. The interaction between 5FU and the liposomal membrane was studied by three methods, and also release profile was obtained. UDL-5FU did penetrate the stratum corneum of human skin. At in vitro experiments, the formulation was more toxic on a human melanoma-derived than on a human keratinocyte-derived cell line. Cells captured liposomes by metabolically active 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 were more toxic than free 5FU. Therefore, this nano-formulation could be useful for topical application in deep skin precancerous lesions with advantages over current treatments. This is the first work that assessed the induction of apoptosis, skin penetration in a Saarbrücken Penetration Model, and the toxicological effects in vivo of an ultradeformable 5FU-loaded formulation.