Tests of BufferGel for Contraception and Prevention of Sexually Transmitted Diseases in Animal Models

Zeitlin, Larry; Hoen, Timothy E.; Achilles, Sharon L.; Hegarty, Tracy A.; Jerse, Ann E.; Kreider, John W.; Olmsted, Stuart S.; Whaley, Kevin J.; Cone, Richard A.; Moench, Thomas R.

doi:10.1097/00007435-200107000-00010

Cited by 84 publications

(68 citation statements)

References 26 publications

(15 reference statements)

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“…KY-N9 and Vena Gel had equivocal or poor results at protecting against infection, presumably due to the need to dilute each product to reach a nontoxic concentration. While Vena Gel was not effective in this study, other compounds that maintain or restore the normal vaginal pH are being pursued and appear effective in animal models (25,60). Unexpectedly, Carraguard did not block infection of PBMCs by the primary isolates.…”

Section: Discussionmentioning

confidence: 76%

In Vitro Comparison of Topical Microbicides for Prevention of Human Immunodeficiency Virus Type 1 Transmission

Dezzutti¹,

James²,

Ramos³

et al. 2004

Antimicrob Agents Chemother

128

106

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A standardized protocol was used to compare cellular toxicities and anti-human immunodeficiency virus type 1 (HIV-1) activities of candidate microbicides formulated for human use. The microbicides evaluated were cellulose acetate phthalate (CAP), Carraguard, K-Y plus nonoxynol-9 (KY-N9), PRO 2000 (0.5 and 4%), SPL7013 (5%), UC781 (0.1 and 1%), and Vena Gel, along with their accompanying placebos. Products were evaluated for toxicity on cervical and colorectal epithelial cell lines, peripheral blood mononuclear cells (PBMCs), and macrophages (MΦ) by using an ATP release assay, and they were tested for their effect on transepithelial resistance (TER) of polarized epithelial monolayers. Anti-HIV-1 activity was evaluated in assays for transfer of infectious HIV-1 from epithelial cells to activated PBMCs and for PBMC and MΦ infection. CAP, Carraguard, PRO 2000, SPL7013, and UC781 along with their placebos were 20- to 50-fold less toxic than KY-N9 and Vena Gel. None of the nontoxic product concentrations disrupted the TER. Transfer of HIV-1Ba-L from epithelial cells to PBMCs and PBMC and MΦ infection with laboratory-adapted HIV-1Ba-L and HIV-1LAI isolates were inhibited by all products except Carraguard, KY-N9, and Vena Gel. KY-N9, Vena Gel, and Carraguard were not effective in blocking PBMC infection with primary HIV-1A, HIV-1C, and HIV-1CRF01-AE isolates. The concordance of these toxicity results with those previously reported indicates that our protocol may be useful for predicting toxicity in vivo. Moreover, our systematic anti-HIV-1 testing provides a rational basis for making better informed decisions about which products to consider for clinical trials

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Section: Discussionmentioning

confidence: 76%

In Vitro Comparison of Topical Microbicides for Prevention of Human Immunodeficiency Virus Type 1 Transmission

Dezzutti¹,

James²,

Ramos³

et al. 2004

Antimicrob Agents Chemother

128

106

View full text Add to dashboard Cite

show abstract

“…Stocks of HIV-1 JR-CSF were prepared, and titers and p24 content were determined as we have previously described (53). HIV-1 exposures were performed essentially as previously described using a total volume of 2 to 10 l (170 ng p24) (11,57).…”

Section: Methodsmentioning

confidence: 99%

One Percent Tenofovir Applied Topically to Humanized BLT Mice and Used According to the CAPRISA 004 Experimental Design Demonstrates Partial Protection from Vaginal HIV Infection, Validating the BLT Model for Evaluation of New Microbicide Candidates

Denton

Othieno

Martinez-Torres

et al. 2011

J Virol

130

150

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“…In addition, systemic medications can lead to significant adverse side effects when high drug concentrations in the circulation are required to elicit a therapeutic response in the CV tract (5). To reduce side effects and achieve localized therapy, recent efforts have increasingly emphasized topical drug delivery methods, such as creams, hydrogels, and inserted devices, to deliver therapeutics to the apical side of the cervix epithelium (6)(7)(8)(9)(10)(11). Apical drug delivery may also be extended to protection against sexual transmission of infections, because neutralizing antibodies and microbicides must act at mucosal surfaces to block the entry of pathogens (12)(13)(14)(15).…”

mentioning

confidence: 99%

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Lai¹,

O’Hanlon

Harrold

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

889

1,012

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Nanoparticles larger than the reported mesh-pore size range (10 -200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (D eff) only 4-and 6-fold lower than that for the same particles in water (at time scale ‫؍‬ 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, D eff was 200-fold lower in mucus than in water. For uncoated particles 100 -500 nm in diameter, D eff was 2,400-to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200-to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery. drug delivery ͉ mucosal tissues ͉ particle tracking ͉ PEG

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Tests of BufferGel for Contraception and Prevention of Sexually Transmitted Diseases in Animal Models

Abstract: The protective efficacy of BufferGel in five of the six animal models suggests that this microbicide warrants clinical evaluation for both contraception and disease prevention.

Cited by 84 publications

References 26 publications

In Vitro Comparison of Topical Microbicides for Prevention of Human Immunodeficiency Virus Type 1 Transmission

In Vitro Comparison of Topical Microbicides for Prevention of Human Immunodeficiency Virus Type 1 Transmission

One Percent Tenofovir Applied Topically to Humanized BLT Mice and Used According to the CAPRISA 004 Experimental Design Demonstrates Partial Protection from Vaginal HIV Infection, Validating the BLT Model for Evaluation of New Microbicide Candidates

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

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