title: New cationic nanovesicular systems containing lysine-based surfactants for topical administration: Toxicity assessment using representative skin cell lines.
abstract: 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 24h 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.
authors.affiliation: Departament de Fisiologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Daniele Rubert
authors.initials: DR
authors.lastname: Nogueira
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Morán
authors.forename: Montserrat
authors.initials: M
authors.lastname: Mitjans
authors.forename: Verónica
authors.initials: V
authors.lastname: Martínez
authors.forename: Lourdes
authors.initials: L
authors.lastname: Pérez
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Vinardell
mesh_terms: D016475:3T3 Cells; D000279:Administration, Cutaneous; D000818:Animals; D002412:Cations; D018929:Cell Culture Techniques; D002460:Cell Line; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D053582:Interleukin-1alpha / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008239:Lysine / Q000737:chemistry*; D051379:Mice; D049329:Nanostructures; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013501:Surface-Active Agents / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods
chemical_list: D002412:Cations; D053582:Interleukin-1alpha; D016209:Interleukin-8; D013501:Surface-Active Agents; D008239:Lysine