In Vitro Surfactant Structure-Toxicity Relationships: Implications for Surfactant Use in Sexually Transmitted Infection Prophylaxis and Contraception

Abstract

BackgroundThe need for woman-controlled, cheap, safe, effective, easy-to-use and easy-to-store topical applications for prophylaxis against sexually transmitted infections (STIs) makes surfactant-containing formulations an interesting option that requires a more fundamental knowledge concerning surfactant toxicology and structure-activity relationships.Methodology/Principal FindingsWe report in vitro effects of surfactant concentration, exposure time and structure on the viability of mammalian cell types typically encountered in the vagina, namely, fully polarized and confluent epithelial cells, confluent but non-polarized epithelial-like cells, dendritic cells, and human sperm. Representatives of the different families of commercially available surfactants – nonionic (Triton X-100 and monolaurin), zwitterionic (DDPS), anionic (SDS), and cationic (CnTAB (n = 10 to 16), C12PB, and C12BZK) – were examined. Triton X-100, monolaurin, DDPS and SDS were toxic to all cell types at concentrations around their critical micelle concentration (CMC) suggesting a non-selective mode of action involving cell membrane destabilization and/or destruction. All cationic surfactants were toxic at concentrations far below their CMC and showed significant differences in their toxicity toward polarized as compared with non-polarized cells. Their toxicity was also dependent on the chemical nature of the polar head group. Our results suggest an intracellular locus of action for cationic surfactants and show that their structure-activity relationships could be profitably exploited for STI prophylaxis in vaginal gel formulations. The therapeutic indices comparing polarized epithelial cell toxicity to sperm toxicity for all surfactants examined, except C12PB and C12BZK, does not justify their use as contraceptive agents. C12PB and C12BZK are shown to have a narrow therapeutic index recommending caution in their use in contraceptive formulations.Conclusions/SignificanceOur results contribute to understanding the mechanisms involved in surfactant toxicity, have a predictive value with regard to their safety, and may be used to design more effective and less harmful surfactants for use in topical applications for STI prophylaxis.

Toxicity Evaluation of Surface Cleaning Preparation Using Different Test Methods / Virsmu tīrīšanas līdzekļa toksiskuma novērtēšana, izmantojot dažādas testa metodes

“…Taken together, our results support the observations in other studies and indicate the necessity to use a complex test-organism battery to evaluate the toxicity of surface cleaning preparations thoroughly. The response of a single test-organism might serve only as a preliminary indicator of toxicity, which can not substitute the whole data set from various test organisms [9] It has been reported previously, that toxicity of surfactants often correlates with their CMC; this indicates that the toxicity is related to destabilization and/or destruction of cell membrane [11]. Most of the MICs acquired in our experiments are below SCP-1 CMC value showing that this is not always the case.…”

“…It is emphasized that a battery of several tests is required to assess toxicity more thoroughly [9]− [10]. Toxicity values of the used surfactant often correlate with its critical micelle concentration (CMC) [11]. CMC is a concentration of surfactant or detergent at which it forms micelles.…”

Mitochondrial Dysfunction Is the Focus of Quaternary Ammonium Surfactant Toxicity to Mammalian Epithelial Cells

“…The onset of cytotoxicity was shown to involve neither membrane disintegration, nor perforation, nor cell lysis, suggesting that the susceptible target had to be intracellular. The high values (6 Ͻ n Ͻ 9) of the Hill coefficients, n, in the logistic fits of our experimental toxicity data (5) suggested that QAC toxicity involved cooperative breakdown of several biochemical processes. The primary site(s) of QAC toxicity would therefore have to be of vital importance to the physiology of the cell.…”

“…MDCK II cells were grown as previously described (5). After achieving complete polarization, the cells were exposed to different concentrations of C 10 TAB for 3 h. At the end of incubation, Opti-MEM medium containing surfactant was replaced by fresh cell culture medium without phenol red, and the viability and caspase 3/7 activity were assayed using an ApoLive-Glo multiplex assay, according to the manufacturer's instructions.…”

“…Bacterial growth in cultures was also shown to be inhibited at concentrations that were sublethal to epithelial cells. We then systematically evaluated the cytotoxicity of the bromide salts of several monoalkyl quaternary ammonium surfactant compounds (QAC) [alkyl-N,N,N-trimethylammonium (C n TAB), N-alkylpyridinium (C n PB), and alkyl-N-benzyl-N,N-dimethylammonium (C n BZK)] toward several mammalian cell lines (5). That study, performed as a function of exposure time and concentration, compared several C n TAB homologues (with C n varying between C 10 and C 16 ), as well as three different headgroups with the same alkyl chain length, C 12 .…”