Development and evaluation of microbicidal hydrogels containing monoglyceride as the active ingredient

A number of medium-chain saturated and long-chain unsaturated fatty acids a cid their monoglycerides were tested against herpes simplex virus (HSV-1) t o determine which lipids were most active during a short incubation time. T he aim was to find which lipid would be preferable as the active ingredient in a virucidal hydrogel formulation for the purpose of preventing transmis sion of pathogens to mucosal membranes, particularly sexually transmitted v iruses, such as herpes simplex virus and human immunodeficiency virus (HIV) , and bacteria, such as Chlamydia trachomatis and Neisseria gonorrheae. The main strategy was that the formulations would be fast-acting, killing larg e numbers of virus or bacteria on contact in a short time, preferably causi ng at least a 10000-fold reduction in virus/bacteria titer in 1-5 min. Mono caprin, the l-monoglyceride of capric acid, and lauric acid were found to b e most active of all the lipids tested, causing a greater than 100000-fold reduction in virus titer in 1 min at a concentration of 20 mM, When tested at a concentration of 10 mM for 1 min, monocaprin was still fully active wh ereas lauric acid had no or neglible activity. It was concluded that monoca prin was most suitable as the active ingredient in a fast-acting virucidal gel formulation, and several hydrogel formulations containing monocaprin we re tested. Formulations where the monoglyceride was dissolved in glycofurol were found to be active against HSV-1. The hydrogel formulations containin g 20 mM monocaprin were highly virucidal in vitro and caused a greater than 100000-fold (HSV-1) inactivation of virus in human semen in 1 min. Formula tions in dilution 1:10 were cytotoxic in monolayers of CV-1 cells, but they were 10-100 fold less cytotoxic than a commercial product which contains 2 % nonoxynol-9.