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

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      Author(s)
      Calienni, M. N.
      Temprana, C. F.
      Prieto, M. J.
      Paolino, D.
      Fresta, M.
      Tekinay, A. B.
      del, Valle, Alonso, S.
      Montanari, J.
      Date
      2018
      Source Title
      Drug Delivery and Translational Research
      Print ISSN
      2190-393X
      Electronic ISSN
      2190-3948
      Publisher
      Springer Verlag
      Volume
      8
      Issue
      3
      Pages
      496 - 514
      Language
      English
      Type
      Article
      Item Usage Stats
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      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 formulationwas 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.
      Keywords
      5-Fluorouracil
      Skin therapy
      Topical delivery
      Ultradeformable liposomes
      Zebrafish
      Permalink
      http://hdl.handle.net/11693/49821
      Published Version (Please cite this version)
      https://doi.org/10.1007/s13346-017-0469-1
      Collections
      • Institute of Materials Science and Nanotechnology (UNAM) 2098
      • Nanotechnology Research Center (NANOTAM) 1125
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