Evaluation of local tolerance of the antiretroviral spermicide (WHI-07)-loaded gel-microemulsion in the porcine female reproductive tract

✍ Scribed by Osmond J. D'Cruz; Fatih M. Uckun

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 461 KB
• Volume: 28
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.1280

✦ Synopsis

Abstract

The local tolerance of the antiretroviral spermicide, WHI‐07 (5‐bromo‐6‐methoxy‐5,6‐dihydro‐3′‐azidothymidine‐5′‐(p‐bromophenyl)‐methoxyalaninyl phosphate)‐loaded gel‐microemulsion was evaluated in a physiologically relevant and sensitive porcine model. Gilts (Duroc) in nonestrus stages of the reproductive cycle received either a single or a daily intravaginal application of 2.0% WHI‐07 via a gel‐microemulsion for 6 days. Cervicovaginal lavage (CVL) fluid was obtained for up to 72 h after a single exposure and the cellular profile and levels of inflammatory cytokines (IL‐1__β__, IL‐8, IFN‐γ and TNF‐α) were quantitated by flow cytometry and chemiluminescence‐based multiplex immunoassay, respectively. The reproductive tract (vagina, cervix, uteri and Fallopian tubes) harvested on day 7 was scored histologically for evidence of mucosal irritation using a new scoring criterion for ten histological endpoints that reflect pathological changes in the epithelial/ subepithelial and vascular/perivascular compartments. When compared with irritant reactions caused by the detergent‐type spermicide, benzalkonium chloride (BZK), the scatter profile of CVL immune cells and basal levels of proinflammatory cytokines (IL‐1__β__, IL‐8, IFN‐γ and TNF‐α) in CVL fluid were unaffected by intravaginal exposure to 2% WHI‐07. Unlike BZK, endpoint histology of the proximal and distal regions of the reproductive tract from gilts treated with 2.0% WHI‐07 via gel‐microemulsion for 6 days did not result in mucosal irritation or alteration in the epithelium, subepithelium/lamina propria, vessels/perivascular tissues and underlying/surrounding muscles. Based on surrogate markers for inflammation, leukocyte profile and histologic data for local tolerance, repeated intravaginal administration of WHI‐07 via gel‐microemulsion as a prophylactic contraceptive is unlikely to cause vaginal irritation. Copyright © 2007 John Wiley & Sons, Ltd.