Inactivation of Hiv by Nonoxynol-9

Malkovsky, Miroslav; Newell, A.; Dalgleish, Angus

doi:10.1016/s0140-6736(88)91440-7

Cited by 81 publications

(35 citation statements)

References 2 publications

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“…This product has been shown to be effective against numerous sexually transmitted pathogens in vitro, including HIV-1 (1,3,4,12,20,21,27,32). However, the in vivo efficacy of nonoxynol-9 against HIV-1 has never been clearly established, and the results of clinical studies are controversial.…”

mentioning

confidence: 99%

Thermoreversible Gel Formulations Containing Sodium Lauryl Sulfate or n -Lauroylsarcosine as Potential Topical Microbicides against Sexually Transmitted Diseases

Roy

Gourde

Piret

et al. 2001

Antimicrob Agents Chemother

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The microbicidal efficacies of two anionic surfactants, sodium lauryl sulfate (SLS) and n-lauroylsarcosine (LS), were evaluated in cultured cells and in a murine model of herpes simplex type 2 (HSV-2) intravaginal infection. In vitro studies showed that SLS and LS were potent inhibitors of the infectivity of HSV-2 strain 333. The concentrations of SLS which inhibit viral infectivity by 50% (50% inhibitory dose) and 90% (90% inhibitory dose) were 32.67 and 46.53 M, respectively, whereas the corresponding values for LS were 141.76 and 225.30 M. In addition, intravaginal pretreatment of mice with thermoreversible gel formulations containing 2.5% SLS or 2.5% LS prior to the inoculation of HSV-2 strain 333 completely prevented the development of genital herpetic lesions and the lethality associated with infection. Of prime interest, no infectious virus could be detected in mouse vaginal mucosa. Both formulations still provided significant protection when viral challenge was delayed until 1 h after pretreatment. Finally, intravaginal application of gel formulations containing 2.5% SLS or 2.5% LS once daily for 14 days to rabbits did not induce significant irritations to the genital mucosa, as demonstrated from macroscopic and histopathologic examinations. These results suggest that thermoreversible gel formulations containing SLS or LS could represent potent and safe topical microbicides for the prevention of HSV-2 and possibly other sexually transmitted pathogens, including human immunodeficiency virus.

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mentioning

confidence: 99%

Thermoreversible Gel Formulations Containing Sodium Lauryl Sulfate or n -Lauroylsarcosine as Potential Topical Microbicides against Sexually Transmitted Diseases

Roy

Gourde

Piret

et al. 2001

Antimicrob Agents Chemother

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“…The authors have commenced an experimental study of the potential of bile salt as a natural-product topically applied vaginal virucide (Sattar and Springthorpe, 1991). It will be particularly interesting to compare toxicity and virucidal efficiency of a wide range of the naturally occurring cholates to establish precise structure relationships and to compare virucidal activity with other synthetic molecules with detergent properties su-ch as 9-nonoxynol or benzalkonium chloride (Oxford et aI., 1971;Malkovsky et et., 1988). Rauscher leukaemia virus.…”

Section: Discussionmentioning

confidence: 99%

“…The non-ionic surfactant nonoxynol-9 has been used widely in clinical practice as a spermicide and has detectable anti-HIV effect in vitro (Malkovsky et al, 1988). However, a recent clinical trial failed to substantiate virucidal activity in vivo (Kreiss et aI., 1992) and local toxicity of the compounds on the tissue of the genital tract has been a concern.…”

Section: Introductionmentioning

confidence: 99%

Sodium Deoxycholate Exerts a Direct Destructive Effect on HIV and Influenza Viruses in vitro and Inhibits Retrovirus-Induced Pathology in An Animal Model

Oxford

Zuckerman

Race

et al. 1994

Antivir Chem Chemother

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“…N-9 has previously been demonstrated to possess in vitro activity against several sexually transmitted disease pathogens, including HIV-1 (24,31). However, high concentrations and/or frequent exposures to these agents resulted in genital irritation and ulceration in clinical trials, which increased the risk for HIV-1 infection (35,39).…”

mentioning

confidence: 99%

Preclinical Evaluation of Synthetic −2 RANTES as a Candidate Vaginal Microbicide To Target CCR5

Kish-Catalone

Gallo

et al. 2006

Antimicrob Agents Chemother

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A potential strategy that can be used to combat the worldwide AIDS epidemic is the development of a vaginal microbicide that prevents the sexual transmission of human immunodeficiency virus type 1 (HIV-1). Certain CC chemokines, including RANTES, MIP-1␣, and MIP-1␤, might facilitate the development of such microbicides since they potently suppress HIV-1 infection by binding to CCR5, the viral coreceptor used by most sexually transmitted strains of HIV-1 to enter host cells. In this study, we evaluated whether a CCR5-specific fragment of RANTES that lacks two N-terminal residues (؊2 RANTES) and possesses especially potent HIV-1 suppressive activity has toxicity profiles conducive to the advancement of testing in candidate microbicide formulations. Analyses were carried out with a synthetic version of the chemokine, which was formulated with either Novasomes 7474, a nonphospholipid liposome, or methylcellulose gel. Dialysis studies demonstrated that the formulated ؊2 RANTES was released from both vehicles and retained anti-HIV-1 activity. Preclinical toxicity studies carried out with Swiss Webster mouse and New Zealand White rabbit vaginal irritation models demonstrated minimal inflammation and minimal adverse changes in cervicovaginal tissue integrity after short-term (10 min) and long-term (24 h) exposure to formulations containing up to 1 mg/ml of ؊2 RANTES. Similarly, no toxicity was observed with formulations of bioactive murine RANTES in the Swiss Webster mouse vaginal irritation model. Overall, these preclinical studies suggest that ؊2 RANTES is suitable for further testing as a candidate anti-HIV-1 microbicide.

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Inactivation of Hiv by Nonoxynol-9

Cited by 81 publications

References 2 publications

Thermoreversible Gel Formulations Containing Sodium Lauryl Sulfate or n -Lauroylsarcosine as Potential Topical Microbicides against Sexually Transmitted Diseases

Thermoreversible Gel Formulations Containing Sodium Lauryl Sulfate or n -Lauroylsarcosine as Potential Topical Microbicides against Sexually Transmitted Diseases

Sodium Deoxycholate Exerts a Direct Destructive Effect on HIV and Influenza Viruses in vitro and Inhibits Retrovirus-Induced Pathology in An Animal Model

Preclinical Evaluation of Synthetic −2 RANTES as a Candidate Vaginal Microbicide To Target CCR5

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