title: Efficacy and safety of a new vaginal contraceptive antimicrobial formulation containing high molecular weight poly(sodium 4-styrenesulfonate).
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 (IC(50) = 5.3 microg/ml) and acrosin (IC(50) = 0.3 microg/ml) and caused the loss of acrosomes from spermatozoa (85% maximal loss by 0.5 microg/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; IC(50)= 16 microg gel/ml) and herpes simplex viruses (HSV-1 and HSV-2; IC(50) = 1.3 and 1.0 microg 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 (IC(50) < 1.0 gel/ml) and Chlamydia trachomatis (IC(50) = 1.2 microg 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.
authors.affiliation: Program for the Topical Prevention of Conception and Disease, Department of Obstetrics and Gynecology, Rush University, Rush-Presbyterian-St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA. lzanevel@rush.edu
authors.forename: Lourens J D
authors.initials: LJ
authors.lastname: Zaneveld
authors.forename: Donald P
authors.initials: DP
authors.lastname: Waller
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anderson
authors.forename: Calvin
authors.initials: C
authors.lastname: Chany
authors.forename: William F
authors.initials: WF
authors.lastname: Rencher
authors.forename: Kenneth
authors.initials: K
authors.lastname: Feathergill
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Diao
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Doncel
authors.forename: Betsy
authors.initials: B
authors.lastname: Herold
authors.forename: Morris
authors.initials: M
authors.lastname: Cooper
mesh_terms: D000176:Acrosin / Q000037:antagonists & inhibitors; D000177:Acrosome / Q000187:drug effects; D000282:Administration, Intravaginal; D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology; D002692:Chlamydia trachomatis / Q000187:drug effects; D003271:Contraceptive Agents, Female / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015497:HIV-1 / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors; D008297:Male; D008970:Molecular Weight; D009344:Neisseria gonorrhoeae / Q000187:drug effects; D011137:Polystyrenes / Q000009:adverse effects / Q000494:pharmacology; D011817:Rabbits; D013083:Sperm Transport / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000201:enzymology / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D003271:Contraceptive Agents, Female; D004791:Enzyme Inhibitors; D011137:Polystyrenes; C003321:polystyrene sulfonic acid; D006821:Hyaluronoglucosaminidase; D000176:Acrosin