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Title: New cationic nanovesicular systems containing lysine-based surfactants for topical administration: Toxicity assessment using representative skin cell lines
Author: Nogueira, Daniele R.
Morán Badenas, María del Carmen
Mitjans Arnal, Montserrat
Martínez Ocaña, Verónica
Pérez Muñoz, Lourdes
Vinardell Martínez-Hidalgo, Ma. Pilar
Keywords: Agents tensioactius
Membranes cel·lulars
Cultiu cel·lular
Citotoxicitat per mediació cel·lular
Surface active agents
Cell membranes
Cell culture
Cell-mediated cytotoxicity
Biological assay
Issue Date: Jan-2013
Publisher: Elsevier B.V.
Abstract: Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Cationic nanovesicles have attracted considerable interest as effective carriers to improve the delivery of biologically active molecules into and through the skin. In this study, lipid-based nanovesicles containing three different cationic lysine-based surfactants were designed for topical administration. We used representative skin cell lines and in vitro assays to assess whether the cationic compounds modulate the toxic responses of these nanocarriers. The nanovesicles were characterized in both water and cell culture medium. In general, significant agglomeration occurred after 24 h incubation under cell culture conditions. We found different cytotoxic responses among the formulations, which depended on the surfactant,cell line (3T3, HaCaT, and THP-1) and endpoint assayed (MTT, NRU, and LDH). Moreover, no potential phototoxicity was detected in fibroblast or keratinocyte cells, whereas only a slight inflammatory response was induced, as detected by IL-1a and IL-8 production in HaCaT and THP-1 cell lines, respectively. A key finding of our research was that the cationic charge position and the alkyl chain length of the surfactants determine the nanovesicles resulting toxicity. The charge on the a-amino group of lysine increased the depletion of cell metabolic activity, as determined by the MTT assay, while a higher hydrophobicity tends to enhance the toxic responses of the nanovesicles. The insights provided here using different cell lines and assays offer a comprehensive toxicological evaluation of this group of new nanomaterials.
Note: Versió postprint del document publicat a:
It is part of: European Journal of Pharmaceutics and Biopharmaceutics, 2013, vol. 83, núm. 1, p. 33-43
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ISSN: 0939-6411
Appears in Collections:Articles publicats en revistes (Bioquímica i Fisiologia)

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