Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent

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

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)426-438
Number of pages13
JournalJournal of Andrology
Volume23
Issue number3
StatePublished - 2002
Externally publishedYes

Fingerprint

Contraceptive Agents
Anti-Infective Agents
Inhibitory Concentration 50
Sexually Transmitted Diseases
Contraception
Spermatozoa
sodium sulfate
cellulose sulfate
Unplanned Pregnancy
Sperm-Ovum Interactions
Cervix Mucus
High-Risk Pregnancy
Hyaluronoglucosaminidase
Human Herpesvirus 2
Neisseria gonorrhoeae
Insemination
Chlamydia trachomatis
Reproductive Health
Human Herpesvirus 1
HIV

Keywords

  • Antifertility
  • Chlamydia
  • HIV
  • HSV
  • Microbicide
  • N. gonorrhoeae

ASJC Scopus subject areas

  • Endocrinology

Cite this

Anderson, R. A., Feathergill, K. A., Diao, X. H., Cooper, M. D., Kirkpatrick, R., Herold, B., ... Zaneveld, L. J. D. (2002). Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent. Journal of Andrology, 23(3), 426-438.

Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent. / Anderson, Robert A.; Feathergill, Kenneth A.; Diao, Xaio Hui; Cooper, Morris D.; Kirkpatrick, Risa; Herold, Betsy; Doncel, Gustavo F.; Chany, Calvin J.; Waller, Donald P.; Rencher, William F.; Zaneveld, Lourens J D.

In: Journal of Andrology, Vol. 23, No. 3, 2002, p. 426-438.

Research output: Contribution to journalArticle

Anderson, RA, Feathergill, KA, Diao, XH, Cooper, MD, Kirkpatrick, R, Herold, B, Doncel, GF, Chany, CJ, Waller, DP, Rencher, WF & Zaneveld, LJD 2002, 'Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent', Journal of Andrology, vol. 23, no. 3, pp. 426-438.
Anderson RA, Feathergill KA, Diao XH, Cooper MD, Kirkpatrick R, Herold B et al. Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent. Journal of Andrology. 2002;23(3):426-438.
Anderson, Robert A. ; Feathergill, Kenneth A. ; Diao, Xaio Hui ; Cooper, Morris D. ; Kirkpatrick, Risa ; Herold, Betsy ; Doncel, Gustavo F. ; Chany, Calvin J. ; Waller, Donald P. ; Rencher, William F. ; Zaneveld, Lourens J D. / Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent. In: Journal of Andrology. 2002 ; Vol. 23, No. 3. pp. 426-438.
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