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

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

Drug Delivery and Translational Research

Springer verlag

Año: 2017 vol. 8 p. 496 - 514

2190-393X

With the aim of improving the topical delivery of the antineoplastic drug 5-fluorouracil (5FU), it was loaded into ultradeformableliposomes composed of soy phosphatidylcholine and sodium cholate (UDL-5FU). The liposome populations had a mean size of70 nm without significant changes in 56 days, and the ultradeformable formulations were up to 324-fold more elastic thanconventional liposomes. The interaction between 5FU and the liposomal membrane was studied by three methods, and alsorelease 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 bymetabolically active processes. In vivo toxicity experiments were carried out in zebrafish (Danio rerio) larvae by studying theswimming activity, morphological changes, and alterations in the heart rate after incubation. UDL-5FU was more toxic than free5FU. Therefore, this nano-formulation could be useful for topical application in deep skin precancerous lesions with advantagesover current treatments. This is the first work that assessed the induction of apoptosis, skin penetration in a Saarbrückenpenetration model, and the toxicological effects in vivo of an ultradeformable 5FU-loaded formulation.