Comparative in vitro spermicidal activity of chelating agents and synergistic effect with nonoxynol-9 on human sperm functionality.
Nonoxynol-9 (N-9), a nonionic surfactant, exerts both spermicidal and anti-viral activities and is the most widely used spermicide. Although N-9 has been regarded as an efficient spermicidal agent for barrier contraception, it has been reported to cause vaginal irritation and allergic vaginitis, and its spermicidal action in the vaginal mucus may be limited. To address these problems, the spermicidal activity of several chelating agents against human semen and their synergistic effect on the spermicidal activity of N-9 were evaluated using computer-assisted semen analysis and a cervical mucus penetration test. Carbopol 934P, chosen as a polymer base for dispersion of N-9 and chelating agent, was also evaluated for its potential spermicidal activity. Chelating agents, such as ethylenediaminetetraacetic acid (EDTA), ethylene bis(oxyethylenenitrilo)tetraacetic acid, and gramicidin, had spermicidal activity against human sperm at the tested concentration range and exerted spermicidal activity within mucus, impeding sperm penetration to the extended cervical space. A synergistic effect was shown between N-9 and EDTA on sperm motility. In dose-response curves, 0.1% EDTA significantly increased binding affinity constant and spermicidal potency of N-9 and reduced the concentration of N-9 at which 50% of the maximum response was observed from 144.5 to 66.4 (micrograms/mL). A synergistic effect was also shown between EDTA and carbopol 934P polymer on inhibition of sperm penetration through the cervical mucus. Therefore, EDTA can be used as a supplementary agent and potentiator for N-9. Development of a carbopol 934P-based drug delivery system for dual controlled release of N-9 in combination with chelating agents seems to be a promising approach for increasing the efficacy of fertility control.
Lee
C H
CH
College of Pharmacy, Rutgers--State University of New Jersey 08854, USA.
Bagdon
R
R
Chien
Y W
YW
D000818:Animals; D002584:Cervix Uteri / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005069:Evaluation Studies as Topic; D005260:Female; D006096:Gramicidin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009093:Mucus / Q000187:drug effects; D017137:Nonoxynol / Q000494:pharmacology*; D012756:Sheep; D013081:Sperm Motility / Q000187:drug effects; D013089:Spermatocidal Agents / Q000494:pharmacology*; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology*
D002614:Chelating Agents; D013089:Spermatocidal Agents; D006096:Gramicidin; D017137:Nonoxynol; D004533:Egtazic Acid; D004492:Edetic Acid