Gel-microemulsions as vaginal spermicides and intravaginal drug delivery vehicles

There is a need for novel formulations to improve the bioavailability throu gh the vaginal/rectal mucosa of microbicidal drug substances against sexual ly transmitted diseases. In addition, there is a need for more effective an d less toxic vaginal spermicides. Here we review our recent discovery of no vel gel-microemulsions (GM) as nontoxic, dual-function intravaginal spermic ides, which can be used as delivery vehicles for lipophilic drug substances targeting sexually transmitted pathogens. We describe the formulation and biologic properties of 2 novel, submicron-particle-size GMs, GM-4 and GM-14 4, which were prepared froth commonly available pharmaceutical excipients. These GMs comprising oil-in-water microemulsion and polymeric hydrogels wer e designed to solubilize lipophilic antiviral/antimicrobial agents and exhi bited rapid spermicidal activity in human semen. Preclinical studies compar ing the in vivo contraceptive efficacy of GM-4 and GM-144 versus nonoxynol- 9-based detergent spermicide (Gynol II) in the rigorous rabbit model confir med the potent contraceptive activity of these GMs. Unlike nonoxynol-9, rep eated intravaginal applications of GM-4 and GM-144 in the rabbit vaginal ir ritation test were not associated with local inflammation or damage of the vaginal mucosa or epithelium. Furthermore, in short-term toxicity studies p erformed in mice, repetitive intravaginal application of spermicidal GM-4 a nd GM-144 for up to 13 weeks was not associated with any local, systemic, o r reproductive toxicity. Spermicidal GMs have unprecedented potential as du al function microbicidal contraceptives to improve vaginal bioavailability of poorly soluble antimicrobial agents without causing significant vaginal damage. (C) 2001 Elsevier Science Inc. All rights reserved.