IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Design and biophysical characterization of 5-fluorouracil-loaded nanosystem for topical skin cancer therapy: in vitro, ex vivo and in vivo studies
Autor/es:
CALIENNI, M. NATALIA; MONTANARI, JORGE; ALONSO, S. DEL VALLE; PRIETO MJ
Lugar:
San Miguel de Tucumán
Reunión:
Congreso; III Latin American Federation of Biophysical Societies (LAFeBS) - IX IberoAmerican Congress of Biophysics - XLV Reunion Anual SAB 2016; 2016
Resumen:
Ultradeformable liposomes (UL) are a drugdelivery nanosystem with an elastic modulus lower than conventional liposomes.UL are capable to penetrate the stratum corneum (SC) of the skin and releasetheir content into the viable epidermis, where neoplastic events occur in skincancer. 5-Fluorouracil (5FU) is an antineoplastic drug, administeredparenterally, with severe side effects. Therefore, the incorporation of 5FU inUL improves specific-site delivery and aims to reduce side effects.UL wereprepared by resuspension with a 5FU solution of a thin lipid film (soyphosphatidylcholine and sodium cholate as border activator), formed by vacuumrotary evaporation. Vesicles were sonicated to reduce in size and lamellarity.Non-encapsulated 5FU was removed by molecular exclusion chromatography. Sizewas determined by DLS and NTA and the stability by ζ potential. The interactiondrug-lipid was assessed by DSC, using Laurdan and MC540 probes. Drug-lipidratio, encapsulation efficiency and release in the time were determined. Sizeand lamellarity were also corroborated by AFM and TEM. In order to study theelastic properties, force distance measurements by AFM and a deformability testin an automated extruder were performed. Free radical scavenging activity wasevaluated using DPPH free radical.In vitro cytotoxicity studies were carriedout in HaCaT and SK-Mel-28 human cell-lines by MTT, Crystal Violet and NeutralRed. Cellular uptake at 4º and 37ºCwas assessed by fluorescent microscopy. Ex vivo penetration studies wereperformed on a Saarbrücken Penetration Model device with human skin explants.Intact skin and transversal sections were studied by confocal microscopy andpenetration profile was quantified in the SC after tape stripping.Finally, invivo nanotoxicological and teratogenic studies were carried out in the animalmodel zebrafish (Danio rerio). ReferencesCevc (1992). Biochim BiophysActa.Montanari (2007). Int J Pharm.Montanari (2010). J Control Release.