ABSTRACT
In the midst of the global epidemics of both unwanted pregnancies and sexually transmitted infections (STIs), options that provide protection are ideal. In the present study, nisin, a known antimicrobial peptide, was evaluated for safety and contraceptive potential in vitro and in vivo in the rabbit. A concentration of 400 microg nisin per ml was found to be spermicidal in vitro, and the effect was dose and time dependent. In vivo studies indicated that intravaginal application of 1 mg nisin blocked conception in rabbits. Repeated application of nisin (50 mg/animal per day) in rabbits for 14 consecutive days did not cause local inflammation or damage to the vaginal epithelium. In addition, the rate of diffusion of nisin into the blood via the vaginal mucosal epithelium, and its clearance from the circulation was found to be rapid. No treatment-related changes were observed in the reproductive performance of rabbits after cessation of treatment. Furthermore, no changes were observed in the gestation period, subsequent growth and survival of neonates in these animals. When male rats were given nisin orally for 13 consecutive weeks, no effect was observed on reproductive performance. The number of pups born, survival and growth of pups were unaltered. The affinity studies of nisin revealed that spermatozoa are more susceptible to nisin than red blood cells and vaginal epithelial cells. We suggest that nisin with spermicidal and antimicrobial properties could serve as a safe vaginal contraceptive for future therapeutic interventions in STIs.
Subject(s)
Anti-Bacterial Agents/pharmacology , Nisin/pharmacology , Spermatocidal Agents/pharmacology , Absorption , Animals , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/toxicity , Cells, Cultured , Drug Administration Schedule , Female , Fertility/drug effects , Male , Models, Animal , Mucous Membrane/metabolism , Nisin/blood , Nisin/toxicity , Pregnancy , Pregnancy Outcome , Rabbits , Rats , Rats, Sprague-Dawley , Spermatocidal Agents/blood , Spermatocidal Agents/toxicity , Vagina/metabolism , Vaginal Creams, Foams, and JelliesABSTRACT
Six healthy women participated in a study of the concentrations of propranolol achieved in plasma after insertion of the drug into the vagina. In four of the women the concentrations were also determined after administration by mouth. The area under the concentration curve for propranolol administered per vaginam was significantly greater than that after oral administration. There were small significant reduction in systolic blood pressure, pulse rate, and forced expiratory volume in one second after vaginal administration but these did not cause any symptomatic side effects. The tolerability of the vagina to drugs and the safety of this form of treatment remain to be determined. Probably further studies of the contraceptive effects of propranolol should be conducted with the dextro isomer of the drug.