Schwartz, J.L. et al. Fourteen-day safety and acceptability study of 6% cellulose sulfate gel: a randomized double-blind Phase I safety study. Contraception 74, 133-140

Harvard University, Cambridge, Massachusetts, United States
Contraception (Impact Factor: 2.34). 09/2006; 74(2):133-40. DOI: 10.1016/j.contraception.2006.02.008
Source: PubMed


Topical microbicides against the human immunodeficiency virus (HIV) 1 that are nonirritating to the female genital epithelium are urgently needed to slow the heterosexual spread of HIV infection. Products that are also effective contraceptives provide additional benefits. Cellulose sulfate (CS) is a noncytotoxic antifertility agent that exhibits in vitro antimicrobial activity against sexually transmitted pathogens, including HIV.
We performed a multicenter, Phase I, placebo-controlled, randomized study to evaluate the genital toxicity of CS. Two cohorts of healthy women used 3.5 ml of 6% CS gel or 3.5 ml of K-Y Jelly, vaginally, bid, for 14 days. The first cohort was sexually abstinent, and the second cohort was sexually active.
CS was associated with only a slightly higher odds ratio (OR) of symptoms of minor urogenital irritation compared to the inactive lubricant K-Y Jelly (OR=2.02, 95% confidence interval=0.90-4.53). In addition, there were minor shifts in some genital flora, but there was no evidence of greater inflammation as evidenced by few colposcopic findings, decreased influx of polymorphonuclear cells and minimal changes in proinflammatory cytokines. Moreover, both products appeared acceptable to most women. Product leakage was identified as more of a problem in sexually abstinent women, but less so in women using the product for sexual intercourse, as would be the case in actual practice.
CS was safe for twice-daily use for 14 days. CS is appropriate for future studies in effectiveness trials.

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    • "Contraceptive Research and Development a Division of the Department of Obstetrics and Gynecology of Eastern Virginia Medical School, 1911 North Fort Myer Drive, Suite 900, Arlington, Virginia 22209) (Schwartz et al., 2006 "
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    ABSTRACT: The development of topical microbicides for intravaginal use to prevent HIV infection requires that the drugs and formulated products be nontoxic to the endogenous vaginal Lactobacillus. In 30min exposure tests we found dapivirine, tenofovir and UC781 (reverse transcriptase inhibitor anti-HIV drugs) as pure drugs or formulated as film or gel products were not deleterious to Lactobacillus species; however, PSC-RANTES (a synthetic CCR5 antagonist) killed 2 strains of Lactobacillus jensenii. To demonstrate the toxicity of formulated products a new assay was developed for use with viscous and non-viscous samples that we have termed the Lactobacillus toxicity test. We found that the vortex mixing of vaginal Lactobacillus species can lead to reductions in bacterial viability. Lactobacillus can survive briefly, about 2s, but viability declines with increased vortex mixing. The addition of heat inactivated serum or bovine serum albumin, but not glycerol, prevented the decrease in bacterial viability. Bacillus atrophaeus spores also demonstrated loss of viability upon extended mixing. We observed that many of the excipients used in film formulation and the films themselves also afford protection from the killing during vortex mixing. This method is of relevance for toxicity for cidal activities of viscous products.
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    • "In addition to the increased susceptibility to HSV, a modest but significant increase in IFN-γ, TNF-α, and IL-1β was detected in vaginal washes, which may have contributed to the epithelial barrier dysfunction. Phase I clinical studies, however, did not report an increase in cervicovaginal cytokines or chemokines upon repeated exposure to CS gel [22]. "
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