Protective effect of a thermoreversible gel against the toxicity of nonoxynol-9

Background and Objectives: One major problem associated with the use of non oxynol-9 is that it can induce local inflammation and ulceration of the vag inal and cervical mucosa that might favor the entry of pathogens, With the aim of developing a gel formulation that could be effective in preventing s exually transmitted infections, the authors have evaluated the capacity of a polyoxypropylene/polyoxyethylene polymer to reduce or eliminate the toxic ity of nonoxynol-9. Study Design: The cytotoxicity of nonoxynol-9 alone or incorporated into th e gel was investigated in human cervical and colon epithelial cells and aft er daily intravaginal application for 2 weeks in rabbits. Results: In vitro experiments showed that nonoxynol-9 was highly toxic to h uman cervical and colon epithelial cells in a dose-dependent manner. Howeve r, the incorporation of the spermicide into the gel markedly reduced its to xicity under the same experimental conditions. In vivo studies showed that in animals treated with nonoxynol-9, the spermicide was very toxic to the v aginal and cervical mucosa as evidenced by the presence of bleeding, irrita tion, epithelial disruption, necrosis, the accumulation of leukocytes in th e submucosa, and the loss of integrity of the epithelial cells. Of prime im portance, the incorporation of nonoxynol-9 into the gel markedly reduced th e toxicity of this potent spermicide/microbicide. Conclusion: The gel formulation could be used as an interesting approach to eliminate the toxicity of potent spermicides/microbicides such as nonoxyno l-9.