Properties of a new, long-lasting vaginal delivery system (LASRS) for contraceptive and antimicrobial agents

In view of the need for improved vaginal formulations that are contraceptiv e, that may prevent transmission of sexually transmitted infections, or bot h, a new delivery system (base formulation; called Long Acting, Sustained R elease of Spermicide, or LASRS) was developed that contains bioadhesive and other ingredients with a long history of safety, and was designed to provi de long-lasting vaginal retention of the formulation and to minimize possib le vaginal irritation caused by incorporated active ingredients. Nonoxynol- 9 (N-9) was added as an active ingredient to study the vaginal irritating p roperties of the formulation and to assess its long-term effectiveness by p ostcoital spermicidal tests. In the first series of experiments, in vitro s tudies showed that the formulation spreads rapidly over a cellulose membran e, forming a bioadhesive layer that remained for at least 12 hours. The sec ond series of experiments addressed the safety of the LASRS suppository in rabbits and primates. Even with a very high concentration of N-9 (20.5%), L ASRS caused only mild/moderate but acceptable irritation in the rabbit. No vaginal irritation occurred in the primate at an even higher concentration (22.5%). During the third series of experiments, the long-lasting vaginal r etention properties were evaluated by postcoital spermicidal tests in the p rimate. LASRS with N-9 was highly spermicidal even when mating was delayed for 12 hours after placement of the formulation. Spermicidal activity was a lso observed when 1) mating was delayed for 24 hours after insertion of the formulation, and 2) if the females were mated 2 or even 3 times without re insertion of the suppository before collection of the vaginal contents. In the final series of tests, the postcoital spermicidal properties of menfego l, another cytotoxic spermicide, were evaluated as were several modificatio ns in the base formulation. Menfegol produced essentially the same results as N-9. Altering the base formulation proved to be nonbeneficial because a decrease in the long-term spermicidal effectiveness was obtained. These res ults suggest that the LASRS suppository has good vehicle properties for the delivery of active ingredients to the vagina.