Use of mandelic acid condensation polymer (SAMMA), a new antimicrobial contraceptive agent, for vaginal prophylaxis

Zaneveld, L. J. D.; Anderson, Robert A.; Diao, Xiao Hui; Waller, Donald P.; Chany, Calvin J.; Feathergill, Kenneth A.; Doncel, Gustavo F.; Cooper, M D; Herold, Betsy C.

doi:10.1016/s0015-0282(02)04210-3

Cited by 38 publications

(74 citation statements)

References 37 publications

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“…PPCM gel is not cytotoxic toward lactobacilli, is not mutagenic, has low acute oral toxicity, and is safe in the rabbit vaginal irritation assay (47). Together, these studies support further development of PPCM, preferably in combination with an RT inhibitor, such as PMPA, or other HIV-specific drugs, as a topical microbicide.…”

Section: Vol 82 2008 Ppcm Blocks Hiv and Prevents Genital Hsv 6581mentioning

confidence: 59%

“…This compound was initially designated sulfuric acidmodified mandelic acid and has since been named PPCM by Yaso Biotechnologies, Inc., on the basis of further clarification of the chemical structure and synthesis (D. P. Waller, unpublished results). Although it has no sulfations or sulfonations, earlier studies indicated that this compound blocks the binding of HIV and HSV to cells by targeting the envelope glycoproteins gp120 and gB-2, respectively, and inhibits viral entry (21,47). The current studies were undertaken to further define the extent of anti-HIV activity of PPCM in cell and explant culture models and to evaluate the anti-HIV activity of PPCM combined in vitro with the candidate microbicide antiretroviral agents tenofovir (PMPA {9-[R-2-(phosphonylmethoxy)propyl]-adenine monohydrate}) (1) and UC-781 (2).…”

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confidence: 99%

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Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model

Mesquita

Wilson

Manlow

et al. 2008

J Virol

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A structurally novel candidate microbicide, PPCM, which is formed from the reaction of D,L-mandelic acid with sulfuric acid, provides activity against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) and is not cytotoxic. The objectives of the current studies were to comprehensively evaluate the activity of PPCM in cell and explant cultures, explore the possibility of combining PPCM with HIV-specific reverse transcriptase inhibitors, and evaluate the efficacy of a formulated gel against genital herpes in a murine model. PPCM inhibited infection by laboratory and clinical R5 and X4 clade B and clade C HIV strains in cell culture. Ectocervical and endocervical tissue explants exposed to HIV-1 BaL in the presence of PPCM were protected (50% inhibitory concentrations [IC 50 ] of 3.9 g/ml for ectocervix and 3.1 g/ml for endocervix), and transfer of virus to target T cells via migratory cells was significantly impaired (IC 50 of 35.7 g/ml for ectocervix and 54.6 g/ml for endocervix). The drug also blocked infection by cell-associated virus. Combinations of PPCM with UC-781 or PMPA in vitro exhibited additive anti-HIV activity. PPCM was incorporated into stable, low-pH gel formulations at concentrations of 0.4% and 4%. Both gels prevented genital herpesvirus infection in mice, even when virus was introduced in human seminal plasma. The abilities of PPCM to inhibit primary HIV isolates, reduce infection by cell-associated virus, and transfer of HIV from migratory to T cells, combined with the complete protection provided by formulated gel against genital herpes, indicate that this drug is an excellent candidate for inclusion in a combination microbicide and would provide protection against both HIV and HSV.

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Section: Vol 82 2008 Ppcm Blocks Hiv and Prevents Genital Hsv 6581mentioning

confidence: 59%

mentioning

confidence: 99%

Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model

Mesquita

Wilson

Manlow

et al. 2008

J Virol

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“…They have also been described to be active against herpes viruses [33]. SAMMA, another anionic polymer, derived from the condensation of mandelic acid, is also a very potent inhibitor of herpes viruses and HIV and has activity against C. trachomatis, N. gonorrhoeae, and sperm [34,35]. Cellulose acetate phthalate is a well-characterized compound displaying antimicrobial activity against an array of STPs, including HIV, which appears to be inhibited through virucidal and receptor-blocking mechanisms [36,37].…”

Section: Cell-entry Inhibitorsmentioning

confidence: 99%

Vaginal microbicides: A novel approach to preventing sexual transmission of HIV

Doncel

Mauck²

2004

Curr HIV/AIDS Rep

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The AIDS epidemic continues its unrelentless expansion. According to the Joint United Nations Programme on HIV/AIDS, there are more than 40 million people living with HIV, and more than 15,000 new infections occur every day. One approach to curbing HIV is the development of topical microbicidal agents or microbicides. These are compounds designed to protect the body's mucosal surfaces from infection by sexually transmitted disease-causing pathogens, including HIV. Several candidates are in preclinical stages; however, only a handful have been tested in humans for safety, and even fewer are ready for clinical efficacy trials. In this update, we describe microbicide research and development, including preclinical screening algorithms, ideal properties, compounds in the pipeline, and future prospects. This review is based on a previous work, which has been updated to contain new information, especially regarding microbicide candidates in preclinical and clinical stages of development.

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“…Our laboratory has used Lact. gasseri as a measure of possible effects of microbicides on normal vaginal flora [3,4,33].…”

Section: Introductionmentioning

confidence: 99%

“…These findings were unexpected because of the similarities among the most prevalent vaginal lactobacillus species, as well as the excellent safety profiles of the microbicides, determined from other testing. Favorable findings include lack of cytotoxic effect on target/host cells used in anti-viral and anti-bacterial assays [4,33,34], minimal effects seen in rabbit vaginal irritation tests [33,34], lack of cytotoxic effects on spermatozoa [3,4,34], and for CS and PSS, successful phase 1 clinical trials [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Differential Sensitivity of Lactobacillus spp. to Inhibition by Candidate Topical Microbicides

Anderson

Aroutcheva

Feathergill

et al. 2009

Probiotics & Antimicro. Prot.

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Preclinical evaluation of vaginal microbicides includes screening against lactobacilli. However, there is no consensus regarding the species to be tested. This study was carried out to determine if results with one species would apply to other species, and to evaluate the utility of turbidometry as a screening tool. One current (PPCM; previously designated sulfuric acid-modified mandelic acid, SAMMA) and two former (cellulose sulfate, CS; and polystyrene sulfonate, PSS) candidate microbicides were evaluated. Bacterial growth was measured turbidometrically and by direct cell count. No microbicide affected Lact. gasseri, measured by either method. Apparent inhibition of Lact. jensenii by CS, PSS, and PPCM, and of Lact. crispatus by CS, occurred with turbidometric measurement. This was not substantiated with direct cell count. PSS and PPCM inhibited Lact. crispatus and Lact. acidophilus with both methods. These findings agree with results from vaginal isolates, which included Lact. gasseri, jensenii, acidophillus, crispatus, rhamnosis, casei, and paracasei. We conclude that sensitivities of similar lactobacilli to at least three microbicides are different. A single species is inadequate for screening vaginal products. Turbidometric evaluation is a sensitive, but not specific, screening method. We recommend that this method be used to screen candidate microbicides against several species of prevalent Lactobacillus species as an initial measure of microbicide safety evaluation.

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Use of mandelic acid condensation polymer (SAMMA), a new antimicrobial contraceptive agent, for vaginal prophylaxis

Cited by 38 publications

References 37 publications

Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model

Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model

Vaginal microbicides: A novel approach to preventing sexual transmission of HIV

Differential Sensitivity of Lactobacillus spp. to Inhibition by Candidate Topical Microbicides

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