In vitro surfactant structure-toxicity relationships: implications for surfactant use in sexually transmitted infection prophylaxis and contraception.
In vitro surfactant structure-toxicity relationships: implications for surfactant use in sexually transmitted infection prophylaxis and contraception.
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DOI：
10.1371/journal.pone.0019850
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Vieira OV
中科院分区：
文献类型：
--
作者：
Inácio ÂS;Mesquita KA;Baptista M;Ramalho-Santos J;Vaz WL;Vieira OV
对女性控制的、廉价的、安全的、有效的、易于使用和易于储存的用于预防性传播感染（STI）的局部应用的需求使得含表面活性剂的制剂成为一种有趣的选择，其需要关于表面活性剂毒理学和结构-活性关系的更基本的知识。我们报告了表面活性剂浓度、暴露时间和结构对阴道中通常遇到的哺乳动物细胞类型的活力的体外影响，即完全极化和融合的上皮细胞、融合但非极化的上皮样细胞、树突状细胞和人精子。检查了市售表面活性剂的不同家族的代表-非离子（Triton X-100和甘油单月桂酸酯）、两性离子（DDPS）、阴离子（SDS）和阳离子（CnTAB（n =10至16）、C12 PB和C12 BZK）。 Triton X-100、甘油单月桂酸酯、DDPS和SDS在其临界胶束浓度（CMC）附近的浓度下对所有细胞类型均具有毒性，表明涉及细胞膜不稳定和/或破坏的非选择性作用模式。所有阳离子表面活性剂在远低于其CMC的浓度下都是有毒的，并且与非极化细胞相比，它们对极化细胞的毒性表现出显着差异。它们的毒性也取决于极性头基的化学性质。我们的结果表明阳离子表面活性剂在细胞内的作用位点，并表明它们的结构-活性关系可以有益地用于阴道凝胶制剂中的STI预防。除C12 PB和C12 BZK外，所有表面活性剂的治疗指数比较极化上皮细胞毒性与精子毒性，不能证明其用作避孕药的合理性。C12 PB和C12 BZK显示出具有狭窄的治疗指数，建议在避孕制剂中谨慎使用。我们的研究结果有助于了解参与表面活性剂毒性的机制，具有预测价值，其安全性，并可用于设计更有效和更少的有害表面活性剂用于STI预防局部应用。
The 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. We 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. Our 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.
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影响因子：
32.4
作者：
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