Microbicidal spermicide or spermicidal microbicide?

Vaginal contraception, the oldest method of fertility regulation that remained virtually forgotten for a few decades has recently come under focal review due to an increase in STDs and HIV infections worldwide. Today it is being considered very strongly that a conceptual microbicidal spermicide can tender protection against pregnancy as well as STDs (including AIDS), simultaneously. However the two activities (spermicidal and microbicidal) need to be integrated in vaginal preparations, as many women across the world may be concerned more about the unwanted pregnancy rather than the STI during a coital act. A strong detergent like nonoxynol-9 (N-9) has been used as a spermicide in many local contraceptive preparations and studies have shown that it also exhibits significant microbicidal activity in vitro. However, recent clinical trials have shown that detergent spermicides do not provide any protection against STDs and AIDS but may in fact even promote their transmission. This anomaly has largely been attributed to their surfactant nature that irritates the vagina and kills the normal vaginal flora making it more susceptible to STD infections. An urgent need for a suitable non-detergent spermicide has thus emerged to replace N-9 in local contraceptive preparations. Anticipating the potential of spermicide-based vaginal contraceptives in the reproductive health of women, a large number of synthetic, non-detergent molecules were designed and evaluated at this Institute over recent years. Simultaneously, a number of natural products from terrestrial plants and marine flora/fauna were also evaluated for spermicidal activity. A local contraceptive preparation incorporating the active ingredient from the fruit pericarp of Sapindus mukorossi has successfully completed Phase III clinical trials in India and is ready for marketing. Recent studies have indicated that in comparison to N-9, this ingredient is much less toxic to Lactobacillus spp. and effectively inhibits the growth of Trichomonas vaginalis in vitro. Other candidate spermicides/microbicides under development worldwide have been reviewed briefly.

[1]  G. Rahav,et al.  Efficacy of a novel pH‐buffering tampon in preserving the acidic vaginal pH during menstruation , 2004, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[2]  D. Weiner,et al.  Single and multiple exposure tolerance study of polystyrene sulfonate gel: a phase I safety and colposcopy study. , 2001, Contraception.

[3]  R. Trager MICROBICIDES:Raising New Barriers Against HIVInfection , 2003, Science.

[4]  F. Uckun,et al.  Structural Requirements for Potent Anti-Human Immunodeficiency Virus (HIV) and Sperm-Immobilizing Activities of Cyclohexenyl Thiourea and Urea Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase1 , 2002, Biology of reproduction.

[5]  A. Dwivedi,et al.  Substituted acrylophenones and related mannich bases as possible spermicides and inhibitors of HIV envelope glycoprotein-CD4 interaction. , 2002, European journal of medicinal chemistry.

[6]  K. Whaley,et al.  Microbicide Efficacy and Toxicity Tests in a Mouse Model for Vaginal Transmission of Chlamydia trachomatis , 2002, Sexually transmitted diseases.

[7]  U. Tamoufé,et al.  Effect of nonoxynol-9 gel on urogenital gonorrhea and chlamydial infection: a randomized controlled trial. , 2002, JAMA.

[8]  M. Bergeron,et al.  Sodium lauryl sulfate, a microbicide effective against enveloped and nonenveloped viruses. , 2002, Current drug targets.

[9]  K. Whaley,et al.  Microbicides for preventing transmission of genital herpes. , 2002, Herpes : the journal of the IHMF.

[10]  W. Stamm,et al.  In Vitro Microbicidal Activities of Cecropin Peptides D2A21 and D4E1 and Gel Formulations Containing 0.1 to 2% D2A21 against Chlamydia trachomatis , 2002, Antimicrobial Agents and Chemotherapy.

[11]  G. Doncel,et al.  An update on vaginal microbicides , 2001, Current infectious disease reports.

[12]  D. Anderson,et al.  The molecular basis of nonoxynol-9-induced vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 transmission. , 2001, The Journal of infectious diseases.

[13]  J. Kirby Nonoxynol-9 may increase HIV transmission risk. , 2001, Positive living.

[14]  S. Baron,et al.  Practical prevention of vaginal and rectal transmission of HIV by adapting the oral defense: use of commercial lubricants. , 2001, AIDS research and human retroviruses.

[15]  B. Richardson,et al.  Evaluation of a Low-Dose Nonoxynol-9 Gel for the Prevention of Sexually Transmitted Diseases: A Randomized Clinical Trial , 2001, Sexually transmitted diseases.

[16]  F. Uckun,et al.  Lack of adverse effects on fertility of female cd‐1 mice exposed to repetitive intravaginal gel–microemulsion formulation of a dual‐function anti‐HIV agent: aryl phosphate derivative of bromo‐methoxy‐zidovudine (compound WHI‐07) , 2001, Journal of applied toxicology : JAT.

[17]  Robert A. Anderson,et al.  Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM). , 2001, Contraception.

[18]  J. Peipert,et al.  Safety and tolerability of BufferGel, a novel vaginal microbicide, in women in the United States. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  J. H. van de Wijgert,et al.  Phase 1 Trial of the Topical Microbicide BufferGel: Safety Results From Four International Sites , 2001, Journal of acquired immune deficiency syndromes.

[20]  J. Wijgert,et al.  Phase 1 trial of the topical microbicide BufferGel: safety results from four international sites. , 2001 .

[21]  D. Weiner,et al.  Single and multiple exposure tolerance study of cellulose sulfate gel: a Phase I safety and colposcopy study. , 2001, Contraception.

[22]  M. Cohen,et al.  Biologic approaches to the prevention of sexual transmission of human immunodeficiency virus. , 2000, Infectious disease clinics of North America.

[23]  F. Uckun,et al.  Novel Thiourea Compounds as Dual-Function Microbicides , 2000, Biology of reproduction.

[24]  F. Uckun,et al.  Evaluation of subchronic (13‐week) and reproductive toxicity potential of intravaginal gel–microemulsion formulation of a dual‐function phenyl phosphate derivative of bromo‐methoxy zidovudine (compound whi‐07) in B6C3F1 mice , 2000, Journal of applied toxicology : JAT.

[25]  S. Hillier,et al.  Effect of Chlorhexidine on Genital Microflora, Neisseria gonorrhoeae, and Trichomonas vaginalis In Vitro , 2000, Sexually transmitted diseases.

[26]  L. Heise,et al.  What's up with nonoxynol-9? , 2000, Reproductive health matters.

[27]  F. Uckun,et al.  Structural Requirements for Potent Human Spermicidal Activity of Dual-Function Aryl Phosphate Derivative of Bromo-Methoxy Zidovudine (Compound WHI-07)1 , 2000, Biology of reproduction.

[28]  F. Uckun,et al.  Evaluation of subchronic (13 weeks) and reproductive toxicity potential of intravaginal gel-microemulsion formulation of a dual-function phenyl phosphate derivative of bromo-methoxy zidovudine (compound WHI-05) in B(6)C(3)F(1) mice. , 2000, Contraception.

[29]  S. Batra,et al.  In search of new chemical entities with spermicidal and anti-HIV activities. , 1999, Bioorganic & medicinal chemistry.

[30]  F. Uckun,et al.  Prophylactic contraceptives for HIV/AIDS. , 1999, Human reproduction update.

[31]  M. Krohn,et al.  The effects of three nonoxynol-9 preparations on vaginal flora and epithelium. , 1999, The Journal of infectious diseases.

[32]  S. Hillier,et al.  Effects of multiple applications of benzalkonium chloride and nonoxynol 9 on the vaginal epithelium in the pigtailed macaque (Macaca nemestrina). , 1999, American journal of obstetrics and gynecology.

[33]  F. Uckun,et al.  WHI-05, a novel bromo-methoxy substituted phenyl phosphate derivative of zidovudine, is a dual-action spermicide with potent anti-HIV activity. , 1999, Contraception.

[34]  F. Uckun,et al.  Synthesis, characterization and preclinical formulation of a dual-action phenyl phosphate derivative of bromo-methoxy zidovudine (compound WHI-07) with potent anti-HIV and spermicidal activities. , 1999, Molecular human reproduction.

[35]  D. Fleming,et al.  From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection. , 1999, Sexually transmitted infections.

[36]  C. Dailard Abortion in context: United States and worldwide. , 1999, Issues in brief.

[37]  M. Gigante,et al.  Sexually transmitted diseases and reproductive tract infections among contraceptive users , 1998, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[38]  F. Uckun,et al.  Aryl phosphate derivatives of bromo-methoxy-azidothymidine are dual-function spermicides with potent anti-human immunodeficiency virus. , 1998, Biology of reproduction.

[39]  H. Ward,et al.  Effect on normal vaginal flora of three intravaginal microbicidal agents potentially active against human immunodeficiency virus type 1. , 1998, The Journal of infectious diseases.

[40]  D. Taylor-Robinson,et al.  Safety study of nonoxynol-9 as a vaginal microbicide: evidence of adverse effects. , 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[41]  S. Hillier,et al.  Effects of Nonoxynol‐9 on Vaginal Microflora and Chlamydial Infection in a Monkey Model , 1996, Sexually transmitted diseases.

[42]  C. Lee Review: in vitro spermicidal tests. , 1996, Contraception.

[43]  A. Bhaduri,et al.  Synthesis and spermicidal activities of dithiocarbamates , 1996 .

[44]  A. Neri,et al.  Bacterial vaginosis: drugs versus alternative treatment. , 1994, Obstetrical & gynecological survey.

[45]  G. Doncel,et al.  Synergistic spermicidal activity of neem seed extract, reetha saponins and quinine hydrochloride. , 1994, Contraception.

[46]  Forrest Jd Timing of reproductive life stages. , 1993 .

[47]  J. Forrest Timing of Reproductive Life Stages , 1993, Obstetrics and gynecology.

[48]  T. Fleming,et al.  Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. , 1992, JAMA.

[49]  S. Niruthisard,et al.  Use of nonoxynol-9 and reduction in rate of gonococcal and chlamydial cervical infections , 1992, The Lancet.

[50]  A. Bruce,et al.  Hydrogen peroxide production by Lactobacillus species: correlation with susceptibility to the spermicidal compound nonoxynol-9. , 1992, The Journal of infectious diseases.

[51]  S. Klebanoff Effects of the spermicidal agent nonoxynol-9 on vaginal microbial flora. , 1992, The Journal of infectious diseases.

[52]  T. Hooton,et al.  Nonoxynol-9: differential antibacterial activity and enhancement of bacterial adherence to vaginal epithelial cells. , 1991, The Journal of infectious diseases.

[53]  B. Jones,et al.  The susceptibility of organisms associated with bacterial vaginosis to spermicidal compounds, in vitro. , 1991, Genitourinary medicine.

[54]  H. Mohri,et al.  Spermicidal activity of menfegol‐coated condom , 2009, Andrologia.

[55]  P. Piot,et al.  Incidence of Uncomplicated Genital Infections in Women Using Oral Contraception or an Intrauterine Device: A Prospective Study , 1990, Sexually transmitted diseases.

[56]  M. Wainberg,et al.  Inactivation of human immunodeficiency virus type 1 in tissue culture fluid and in genital secretions by the spermicide benzalkonium chloride , 1990, Journal of clinical microbiology.

[57]  S. Gove,et al.  Oral contraceptives, Chlamydia trachomatis infection, and pelvic inflammatory disease. A word of caution about protection. , 1985, JAMA.

[58]  B. S. Setty,et al.  Screening of Indian plants for biological activity: Part VII--Spermicidal activity of Indian plants. , 1977, Indian journal of experimental biology.

[59]  B. S. Setty,et al.  Spermicidal potential of saponins isolated from Indian medicinal plants. , 1976, Contraception.

[60]  G. Bernstein Physiological aspects of vaginal contraception a review , 1974 .

[61]  G. Bernstein Physiological aspects of vaginal contraception. , 1974, Contraception.

[62]  S. Segal Fertility regulation. , 1967, The Journal of practical nursing.