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Title

New cationic nanovesicular systems containing lysine-based surfactants for topical administration: Toxicity assessment using representative skin cell lines

AuthorsNogueira, Daniele Rubert; Carmen Morán, Maria Del; Mitjans, Montserrat; Martínez, Verónica Laura; Pérez, Lourdes F.; Vinardell, María Pilar
KeywordsCationic nanovesicles
Cell culture
Cytotoxicity
Inflammatory response
Lysine-based surfactants
Skin drug delivery
Issue DateJan-2013
PublisherElsevier
CitationEuropean Journal of Pharmaceutics and Biopharmaceutics 83(1): 33-43(2013)
AbstractCationic 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-1α 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 α-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. © 2012 Elsevier B.V. All rights reserved.
Publisher version (URL)http://dx.doi.org/10.1016/j.ejpb.2012.09.007
URIhttp://hdl.handle.net/10261/131494
DOI10.1016/j.ejpb.2012.09.007
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