%0 Journal Article
%T Decreased cervical epithelial sensitivity to nonoxynol-9 (N-9) after four daily applications in a murine model of topical vaginal microbicide safety
%A Karissa Lozenski
%A Robert Ownbey
%A Brian Wigdahl
%A Tina Kish-Catalone
%A Fred C Krebs
%J BMC Pharmacology and Toxicology
%D 2012
%I BioMed Central
%R 10.1186/2050-6511-13-9
%X To evaluate an association between application frequency and N-9 toxicity, experiments were performed using a mouse model of cervicovaginal microbicide safety. In this model system, changes in cervical and vaginal epithelial integrity, cytokine release, and immune cell infiltration were assessed after single and multiple exposures to N-9.After the initial application of N-9 (aqueous, 1%), considerable damage to the cervical epithelium (but not the vaginal epithelium) was observed as early as 10 min post-exposure and up to 8 h post-exposure. Subsequent daily exposures (up to 4 days) were characterized by diminished cervical toxicity relative to single exposures of like duration. Levels of pro-inflammatory cytokines released into the cervicovaginal lumen and the degree of CD14-positive immune cell infiltration proximal to the cervical epithelium were also dependent on the number of N-9 exposures.Rather than causing cumulative cervical epithelial damage, repeated applications of N-9 were characterized by decreased sensitivity to N-9-associated toxicity and lower levels of immune cell recruitment. These results provide new insights into the failure of N-9-based microbicides and illustrate the importance of considering multiple exposure protocols in pre-clinical microbicide development strategies.The global human immunodeficiency virus type 1 (HIV-1) epidemic currently includes approximately 33 million HIV-1-infected people worldwide, with a particularly high incidence of infection (~23 million individuals) in Sub-Saharan Africa [1]. Since the discovery of HIV-1 over 30 years ago, the face of this global epidemic has changed dramatically, with heterosexual intercourse now considered the predominant route for the spread of the virus [1]. As a result, women are at much greater risk for acquiring HIV-1 and have a much greater need for methods that effectively reduce or eliminate the risk of infection during sexual intercourse. Although condoms (male and female) are highly e
%K Microbicide
%K N-9
%K Cervix
%K Mouse
%K Toxicity
%U http://www.biomedcentral.com/2050-6511/13/9