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

• Published in: European journal of pharmaceutics and biopharmaceutics 2013-01, Vol.83 (1), p.33-43
• Main Authors: Nogueira, Daniele Rubert, Carmen Morán, M., Mitjans, Montserrat, Martínez, Verónica, Pérez, Lourdes, Pilar Vinardell, M.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Administration, Cutaneous; Agents tensioactius; Animals; Bioassaigs; Biological assay; Cationic nanovesicles; Cations; Cell culture; Cell Culture Techniques; Cell Line; Cell Line, Tumor; Cell membranes; Cell-mediated cytotoxicity; Citotoxicitat per mediació cel·lular; Cultiu cel·lular; Cytotoxicity; Drug Delivery Systems; Fibroblasts - drug effects; Fibroblasts - metabolism; Humans; Hydrophobic and Hydrophilic Interactions; Inflammatory response; Interleukin-1alpha - metabolism; Interleukin-8 - metabolism; Keratinocytes - drug effects; Keratinocytes - metabolism; Lysine - chemistry; Lysine-based surfactants; Membranes cel·lulars; Mice; Nanostructures; Nanotoxicologia; Nanotoxicology; Skin - drug effects; Skin - metabolism; Skin drug delivery; Surface active agents; Surface-Active Agents - toxicity; Toxicity Tests - methods
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2012.09.007

Nanovesicles containing cationic lysine-based surfactants were designed for topical administration and characterized by TEM and DLS. It was studied whether the inclusion of the amphiphiles in such nanocarriers determined their cytotoxicity, phototoxicity and inflammatory response in representative skin cell lines. We found that the toxicity of the nanovesicles depended on the structural parameters of the surfactants, the cell line and the in vitro endpoint. 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.