CONICET | Buscador de Institutos y Recursos Humanos

Characterization and skin penetration of 5-fluorouracil-loaded ultradeformable liposomes for topical delivery 1. Objectives To characterize physico-chemically a novel formulation of ultradeformable liposomes for skin delivery of 5-fluorouracil antitumoral drug and to evaluate the skin penetration ex vivo.2. IntroductionUltradeformable liposomes (UL) are capable to penetrate the stratum corneum impelled by the dehydration pressure caused by the transdermal humidity gradient. Their lower elastic modulus in comparison to conventional liposome formulations is the key to that particular feature that allows them to release their content into the viable epidermis, where neoplasic events occur in skin cancer. The incorporation of drugs in UL improves specific-site delivery and aims to reduce the collateral effects, increase the half-life of the drug and reduce the effective dose. 5-Fluorouracil is a pyrimidine analogue used for oncologic treatment over 40 years. 3. Materials and Methods5-fluorouracil-loaded ultradeformable liposomes were prepared by resuspension of a thin lipid film (soy phosphatidylcholine and sodium cholate as border activator) in a 5-fluorouracil solution in Tris Buffer, followed by size and lamellarity reduction by sonication. Size was determined by dynamic light scattering, stability by zeta potential and the interaction drug-lipid by differential scanning calorimetry. Size and lamellarity were corroborated by AFM and TEM. Force distance measurements were also performed by AFM in order to study the elastic properties of the formulation.Human skin explants for penetration studies were obtained from plastic surgery discards. Liposomes with double fluorescent labeling (FITC and Rhodamine) were non-occlusively applied on a Saarbrücken Penetration Model device, and both intact skin and transversal sections were studied by confocal microscopy (Figure 1). 5-Fluorouracil and the drug co-encapsulated with the double fluorescent labeling were quantified in the stratum corneum (SC) after tape stripping. 4. References[1] Betancourt, T., et al., Controlled release and nanotechnology, in Nanotechnology in Drug Delivery, 2009, Springer. p. 283-312.[2] Cevc, G. and G. Blume, Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim Biophys Acta, 1992. 1104(1): p. 226-32.[3] Longley, D.B., D.P. Harkin, and P.G. Johnston, 5-Fluorouracil: mechanisms of action and clinical strategies.Nat Rev Cancer, 2003. 3(5): p. 330-338.[4] Montanari, J., et al., Photodynamic ultradeformable liposomes: Design and characterization. Int J Pharm, 2007. 330(1-2): p. 183-94.[5] Montanari, J., et al., Sunlight triggered photodynamic ultradeformable liposomes against Leishmania braziliensis are also leishmanicidal in the dark. J Control Release, 2010. 147(3): p. 368-76.[6] Montanari, J., et al., Nanoberries for topical delivery of antioxidants. J Cosmet Sci, 2013. 64(6): p. 469-81.