Preclinical evaluation of sodium cellulose sulfate (Ushercell) as a contraceptive antimicrobial agent.
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 microg/mL), herpes viruses, HSV-1 (IC50 = 59 ng/mL) and HSV-2 (lC50 = 24 ng/mL), Neisseria gonorrhoeae (IC50 = 2 microg/mL), and Chlamydia trachomatis (IC50 = 78 microg/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.
Anderson
Robert A
RA
Department of Obstetrics and Gynecology, Rush Medical Center, Chicago, Illinois 60612, USA. randerso@rush.edu
Feathergill
Kenneth A
KA
Diao
Xaio-Hui
XH
Cooper
Morris D
MD
Kirkpatrick
Risa
R
Herold
Betsy C
BC
Doncel
Gustavo F
GF
Chany
Calvin J
CJ
Waller
Donald P
DP
Rencher
William F
WF
Zaneveld
Lourens J D
LJ
D000177:Acrosome / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology; D002482:Cellulose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002690:Chlamydia Infections / Q000517:prevention & control; D003271:Contraceptive Agents, Female / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015658:HIV Infections / Q000517:prevention & control; D006561:Herpes Simplex / Q000517:prevention & control; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors; D007778:Lactobacillus / Q000187:drug effects; D008297:Male; D011817:Rabbits; D015231:Sexually Transmitted Diseases, Bacterial / Q000517:prevention & control*; D013094:Spermatozoa / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D003271:Contraceptive Agents, Female; D004791:Enzyme Inhibitors; D002482:Cellulose; C020254:cellulose sulfate; D006821:Hyaluronoglucosaminidase