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

Abstract

With the aim of improving the topical delivery of the antineoplastic 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 was 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.

Comparative skin penetration profiles of formulations including ultradeformable liposomes as potential nanocosmeceutical carriers

“…Nevertheless, rheological and viscoelastic properties of the vehiculatled formulations should be assessed along time, together with longer stability studies, in order to determine the shelf life of final products. UDL prepared under very similar conditions has been proved to be stable in aqueous suspension for at least 2 months 19 …”

“…After incubation, some skin explants were fixed with pins on a polystyrene block, and then, 20 sequential samples from the SC of each skin piece were obtained by tape stripping 18 . In this technique, an adhesive tape is charged with 2 kg for 10 seconds on the skin sample and then retired to obtain a portion of SC 19 . The remaining skin, that is viable epidermis and dermis (VED), was ground.…”

Nanoferulic: From a by‐product of the beer industry toward the regeneration of the skin

“…After incubation (24 hours at 37°C), cell monolayers were washed twice with PBS and cytotoxicity was determined by the MTT assay, which measures the mitochondrial succinate dehydrogenase activity of cells 24 to find a nontoxic range of work. Empty ultradeformable liposomes (ie, NF without FA) were used as control 25 …”

Zebrafish (Danio rerio) model as an early stage screening tool to study the biodistribution and toxicity profile of doxorubicin-loaded mixed micelles

“…The heart rate and morphological changes were assessed at 72 hpi as described by Calienni et al, (Calienni et al, 2017b…”

“…Regarding antitumoral drugs, the zebrafish model allows to determinate parameters such as lethal dose, acute toxicity, teratogenicity and specific-organ toxicity, in particular of the heart and the nervous system (Calienni et al, 2017b;Raldúa and Piña, 2014). Also, the transparent body of zebrafish allows studying the biodistribution of actives and drug delivery systems by diverse imaging techniques (Lillo et al, 2018).…”