Efficacy and safety of a new vaginal contraceptive antimicrobial formulation containing high molecular weight poly(sodium 4-styrenesulfonate)

Lourens J.D. Zaneveld, Donald P. Waller, Robert A. Anderson, Calvin Chany, William F. Rencher, Kenneth Feathergill, Xiao Hui Diao, Gustavo F. Doncel, Betsy Herold, Morris Cooper

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62 Scopus citations

Abstract

Host cell infection by sexually transmitted disease (STD)-causing microbes and fertilization by spermatozoa may have some mechanisms in common. If so, certain noncytotoxic agents could inhibit the functional activity of both organisms. High molecular mass poly(sodium 4-styrenesulfonate) (T-PSS) may be one of these compounds. T-PSS alone (1 mg/ml) or in a gel (2% or 5% T-PSS) completely prevented conception in the rabbit. Contraception was not due to sperm cytotoxicity or to an effect on sperm migration. However, T-PSS inhibited sperm hyaluronidase (IC50 = 5.3 μg/ml) and acrosin (IC50 = 0.3 μg/ml) and caused the loss of acrosomes from spermatozoa (85% maximal loss by 0.5 μg/ml). T-PSS (5% in gel) also reduced sperm penetration into bovine cervical mucus (73% inhibition by 1 mg gel/mi). T-PSS (5% in gel) inhibited human immunodeficiency virus (HIV; IC50 = 16 μg gel/mi) and herpes simplex viruses (HSV-1 and HSV-2; IC50 = 1.3 and 1.0 μg gel/ml, respectively). The drug showed high efficacy against a number of clinical isolates and laboratory strains. T-PSS (5% in gel) also inhibited Neisseria gonorrhea (IC50 < 1.0 gel/mi) and Chlamydia trachomatis (IC50 = 1.2 μg gel/ml) but had no effect on lactobacilli. These results imply that T-PSS is an effective functional inhibitor of both spermatozoa and certain STD-causing microbes. The noncytotoxic nature should make T-PSS safe for vaginal use. T-PSS was nonmutagenic in vitro and possessed an acute oral toxicity of >5 g/kg (rat). Gel with 10% T-PSS did not irritate the skin or penile mucosa (rabbit) and caused no dermal sensitization (guinea pig). Vaginal administration of the 5% T-PSS gel to the rabbit for 14 consecutive days caused no systemic toxicity and only mild (acceptable) vaginal irritation. T-PSS in gel form is worthy of clinical evaluation as a vaginal contraceptive HIV/STD preventative.

Original languageEnglish (US)
Pages (from-to)886-894
Number of pages9
JournalBiology of Reproduction
Volume66
Issue number4
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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Keywords

  • Fertilization
  • Sperm
  • Sperm motility and transport
  • Toxicology
  • Vagina

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

Cite this

Zaneveld, L. J. D., Waller, D. P., Anderson, R. A., Chany, C., Rencher, W. F., Feathergill, K., Diao, X. H., Doncel, G. F., Herold, B., & Cooper, M. (2002). Efficacy and safety of a new vaginal contraceptive antimicrobial formulation containing high molecular weight poly(sodium 4-styrenesulfonate). Biology of Reproduction, 66(4), 886-894. https://doi.org/10.1095/biolreprod66.4.886