GM-144, a novel lipophilic vaginal contraceptive gel-microemulsion.
In a systematic effort to develop a dual-function intravaginal spermicide as well as a drug delivery vehicle against sexually transmitted pathogens, a submicron particle size (30-80 nm), lipophilic and spermicidal gel-microemulsion (viz GM-144) containing the pharmaceutical excipients propylene glycol, Captex 300, Cremophor EL, Phospholipon 90G, Rhodigel, Pluronic F-68, and sodium benzoate was formulated. GM-144 completely immobilized sperm in human or rabbit semen in less than 30 seconds. Therefore, the in vivo contraceptive potency of intravaginally applied GM-144 was compared in the standard rabbit model to those of the detergent spermicide, nonoxynol-9 (N-9)-containing formulation. Eighty-four ovulated New Zealand White rabbits in subgroups of 28 were artificially inseminated with and without intravaginal administration of GM-144 or 2% N-9 (Gynol II) formulation and allowed to complete term pregnancy. GM-144 showed remarkable contraceptive activity in the rigorous rabbit model. When compared with control, intravaginal administration of GM-144 and Gynol II resulted in 75% and 70.8% inhibition of fertility (P <.0001 versus control, Fisher's exact test), respectively. Thus, GM-144 as a vaginal contraceptive was as effective as the commercially available N-9 gel. In the rabbit vaginal irritation test, none of the 6 rabbits given daily intravaginal application of spermicidal GM-144 for 10 days developed epithelial ulceration, edema, leukocyte influx, or vascular congestion characteristic of inflammation (total score = 5). Therefore, GM-144 has the potential to become a clinically useful safe vaginal contraceptive and a vehicle for formulating lipophilic drugs used in reducing the risk of heterosexual transmission of sexually transmitted diseases.
D'Cruz
O J
OJ
Department of Reproductive Biology, Drug Discovery Program, Parker Hughes Institute, St Paul, MN, USA. odcruz@ih.org
Yiv
S H
SH
Uckun
F M
FM
D000282:Administration, Intravaginal; D000818:Animals; D001696:Biomechanical Phenomena / Q000379:methods / Q000706:statistics & numerical data; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D004655:Emulsions / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D017137:Nonoxynol / Q000494:pharmacology; D009821:Oils / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D011247:Pregnancy; D011817:Rabbits; D012661:Semen / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013081:Sperm Motility / Q000187:drug effects; D013089:Spermatocidal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D014621:Vagina / Q000187:drug effects / Q000473:pathology; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology
D003271:Contraceptive Agents, Female; D004337:Drug Carriers; D004655:Emulsions; D009821:Oils; D013089:Spermatocidal Agents; D014622:Vaginal Creams, Foams, and Jellies; D017137:Nonoxynol