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Preclinical Evaluation of Sodium Cellulose Sulfate (Ushercell) as a Contraceptive Antimicrobial Agent

MORRIS D. COOPER

RISA KIRKPATRICK

BETSY C. HEROLD

From the TOPCAD Program and ^* Department of Obstetrics and Gynecology, Rush Medical Center, Chicago, Illinois; Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois; Department of Pediatric Infectious Diseases, Mount Sinai School of Medicine, New York, New York; Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia; ^|| Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago, Chicago, Illinois; and ^¶ Contraceptive Research and Development Program, Arlington, Virginia.

Correspondence to: Robert A. Anderson Jr, Ob/Gyn Research, Rush Medical Center, Chicago, IL 60612 (e-mail: randerso{at}rush.edu ).

The spread of sexually transmitted infections (STIs) and limited methods for control of pregnancies presents high risks to the reproductive health of women. Methods controlled by women and directed toward disease prevention and contraception are needed. We report on preclinical studies of the biological properties of sodium cellulose sulfate (Ushercell) currently being developed for use as a topical contraceptive antimicrobial agent. Ushercell was evaluated with tests designed to identify its contraceptive and antimicrobial properties. Ushercell inhibits hyaluronidase (reversible; IC₅₀ = 1.7 mg/mL), impairs sperm penetration of cervical mucus (approximately 70% inhibition at 1 mg/mL), and acts as a stimulus for acrosomal loss (IC₅₀ = 52 ng/mL). It prevents conception in rabbits when added to spermatozoa (approximately 95% inhibition at 1 mg/mL) or when vaginally applied (complete contraception by 45 mg) before insemination. However, up to 50 mg/mL, Ushercell does not irreversibly immobilize spermatozoa, suggesting that Ushercell is not cytotoxic. Ushercell has a broad spectrum of antimicrobial activity in vitro. Inhibited microbes include human immunodeficiency viruses (different laboratory strains and clinical isolates; IC₅₀ values range from 3 to 78 µg/mL), herpes viruses, HSV-1 (IC₅₀ = 59 ng/mL) and HSV-2 (IC₅₀ = 24 ng/mL), Neisseria gonorrhoeae (IC₅₀ = 2 µg/mL), and Chlamydia trachomatis (IC₅₀ = 78 µg/mL). In contrast, Ushercell does not inhibit growth of beneficial vaginal bacteria, Lactobacillus gasseri, at 5 mg/mL. These results suggest that the antimicrobial effects of Ushercell are selective, and not likely mediated by nonspecific cytotoxic mechanisms. These data provide the basis for further clinical development of Ushercell as a vaginal agent to prevent unplanned pregnancy and STIs.

     Key words: Antifertility, microbicide, HIV, HSV, chlamydia, N. gonorrhoeae

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