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Efficacy and Safety of a New Vaginal Contraceptive Antimicrobial Formulation Containing High Molecular Weight Poly(Sodium 4-Styrenesulfonate)¹

^a Program for the Topical Prevention of Conception and Disease, Department of Obstetrics and Gynecology, Rush University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612 ^b Program for the Topical Prevention of Conception and Disease, Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago, Chicago, Illinois 60612 ^c Contraceptive Research and Development Program, Eastern Virginia Medical School, Norfolk, Virginia 23507 ^d Department of Pediatric Infectious Diseases, Mount Sinai Medical Center, New York, New York 10029 ^e Department of Medical Microbiology and Immunology, Southern Illinois University, Springfield, Illinois 62794

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/ml). T-PSS (5% in gel) inhibited human immunodeficiency virus (HIV; IC₅₀= 16 µg gel/ml) 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/ml) 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.

First decision: 19 May 2001.

¹ Support for this project was provided by the CICCR Program of the Contraceptive Research and Development Program, Eastern Virginia Medical School (contracts CIG-96-01 and CIG-00-48), the Rockefeller Foundation (grant RF95021), and the National Institute for Allergy and Infectious Diseases (grant PO1 A137940). The views expressed by the authors do not necessarily reflect the views of the funding agencies.

² Correspondence: L. Zaneveld, Section of Ob/Gyn Research, Rush-Presbyterian-St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612. FAX: 312 942 2771; lzanevel{at}rush.edu

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