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

Abstract

A number of medium-chain saturated and long-chain unsaturated fatty acids and their monoglycerides were tested against herpes simplex virus (HSV-1) to determine which lipids were most active during a short incubation time. The aim was to find which lipid would be preferable as the active ingredient in a virucidal hydrogel formulation for the purpose of preventing transmission of pathogens to mucosal membranes, particularly sexually transmitted viruses, 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 large numbers of virus or bacteria on contact in a short time, preferably causing at least a 10000-fold reduction in virus/bacteria titer in 1-5 min. Monocaprin, the 1-monoglyceride of capric acid, and lauric acid were found to be 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 whereas lauric acid had no or negligible activity. It was concluded that monocaprin was most suitable as the active ingredient in a fast-acting virucidal gel formulation, and several hydrogel formulations containing monocaprin were tested. Formulations where the monoglyceride was dissolved in glycofurol were found to be active against HSV-1. The hydrogel formulations containing 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. Formulations 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.

A Review of Current Intravaginal Drug Delivery Approaches Employed for the Prophylaxis of HIV/AIDS and Prevention of Sexually Transmitted Infections

“…C31G cream (Savvy™, Cellegy Pharmaceuticals, Inc, San Francisco, CA, USA) comprises a broad-spectrum antimicrobial and spermicidal agent namely cetyl betaine and myristamine oxide that displays activity against bacteria, fungi, yeasts, and enveloped viruses (125) (Table IV). These effects occur once the microbicidal agent diffuses through the cream, which is formulated with hydroxyethylcellulose that also acts as a surface-active microbicide.…”

Antimicrobial properties of 1‐monoacylglycerols prepared from undecanoic (C11:0) and undecenoic (C11:1) acid

“…Kabara et al [25] found out that antimicrobial activity of MAG prepared from undecanoic (C11:0), undecenoic (C11:1), lauric (C12:0) and tridecanoic (C13:0) acids against Gram-positive bacteria (Streptococcus feacalis, S. pyogenes, S. aureus) and yeasts (C. albicans, Saccharomyces cerevisiae) increased in comparison with their corresponding fatty acids. In the study by Kristmudsdottir et al [26], virucidal properties of saturated MAG with mediumchain fatty acids and unsaturated MAG with long-chain fatty acids were followed. MAG C10:0 (20 mmol/L) was the most efficient one against herpes simplex virus (HSV-1) in vitro and authors also assume its potency against another viruses (HIV) and bacteria causing sexually transmitted diseases.…”

In Vitro Killing of Candida albicans by Fatty Acids and Monoglycerides

“…Medium-chain free fatty acids and their corresponding 1-monoglycerides have been found to have a broad spectrum of microbicidal activity against enveloped viruses and various bacteria in vitro (5,7,11,12,14), including pathogens like herpes simplex virus (8,12), Neisseria gonorrhoeae (2), Chlamydia trachomatis (1), group A streptococci, group B streptococci (GBS), and Staphylococcus aureus (3). The mechanism by which these lipids kill bacteria is not known, but electron microscope studies indicate that they disrupt cell membranes (1,3,12).…”