Characterization and skin penetration of 5-fluorouracil-loaded ultradeformable liposomes for topical delivery

CALIENNI, M. NATALIA; TOPAL, AHMET EMIN; ÜREL, MUSTAFA; ALONSO, S. DEL VALLE; MONTANARI, JORGE A.M.

Ankara

Congreso; NANOTR-11: 11th Conference on Nanoscience and Nanotechnology in Turkey; 2015

Middle East Technical University

Characterizationand skin penetration of 5-fluorouracil-loaded ultradeformable liposomes for topicaldelivery  M. Natalia Calienni1, Ahmet Emin Topal2, Mustafa Ürel2, Silvia del V. Alonso1 and Jorge M. Montanari1,2* 1BiomembraneLab, GBEyB, IMBICE-CONICET (National Council of Science and TechnologyResearch), Department of Science andTechnology, National University of Quilmes (UNQ), Buenos Aires, Argentina2UNAM- National Nanotechnology Research Center, Institute of Materials Science andNanotechnology, Bilkent University, Ankara, Turkey*Presenter:jmontanari@unq.edu.ar  1. Objectives Stratum corneum   outside   viable epidermis   To characterize physico-chemically a novel formulationof ultradeformable liposomes for skin delivery of 5-fluorouracil antitumoraldrug and to evaluate the skin penetration exvivo. 2. IntroductionUltradeformable liposomes (UL)are capable to penetrate the stratumcorneum impelled by the dehydration pressure caused by the transdermalhumidity gradient. Their lower elastic modulus in comparison to conventionalliposome formulations is the key to that particular feature that allows them torelease their content into the viable epidermis, where neoplasic events occurin skin cancer. The incorporation of drugs in ULimproves specific-site delivery and aims to reduce the collateral effects,increase the half-life of the drug and reduce the effective dose. 5-Fluorouracilis a pyrimidine analogue used for oncologic treatment over 40 years.   3. Materials and Methods5-fluorouracil-loaded ultradeformable liposomeswere prepared by resuspension of a thin lipid film (soy phosphatidylcholine andsodium cholate as border activator) in a 5-fluorouracil solution in Tris Buffer,followed by size and lamellarity reduction by sonication. Size was determinedby dynamic light scattering, stability by zeta potential and the interactiondrug-lipid by differential scanning calorimetry. Size and lamellarity werecorroborated by AFM and TEM. Force distance measurements were also performed byAFM in order to study the elastic properties of the formulation.Human skin explants for penetration studies wereobtained from plastic surgery discards. Liposomes with double fluorescentlabeling (FITC and Rhodamine) were non-occlusively applied on a Saarbrücken PenetrationModel device, and both intact skin and transversal sections were studied byconfocal microscopy (Figure 1). 5-Fluorouracil and the drug co-encapsulatedwith the double fluorescent labeling were quantified in the stratum corneum(SC) after tape stripping.       Figure 1. Skin transversal section of anexplant incubated with double labeled ultradeformable liposomes loaded with5-fluorouracil by confocal microscopy at 20X.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 penetrateinto intact skin owing to the transdermal osmotic gradients and hydrationforce. 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 andclinical 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 triggeredphotodynamic ultradeformable liposomes against Leishmania braziliensis are alsoleishmanicidal 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.