Document Type

Article

Publication Date

11-10-2025

Identifier

DOI: 10.1016/j.ijpharm.2025.126120

Abstract

Lactic acid is the most abundant organic weak acid in the healthy human vagina and plays a pivotal role in maintaining an acidic vaginal environment protective against exogenous bacteria and viruses. However, in dysbiotic or non-optimal vaginal environments, significantly decreased concentrations of lactobacilli result in reduced lactic acid production, increased vaginal pH, and enhanced risk of sexually transmitted infections (including human immunodeficiency virus), and bacterial vaginosis. Various gel-based products are marketed to administer lactic acid vaginally for the treatment of bacterial vaginosis and non-hormonal contraception, and there is interest in developing vaginal ring products for sustained/controlled release of lactic acid. However, lactic acid is not compatible with the most common addition-cure type of silicone elastomer used to manufacture vaginal rings; the carboxylic acid group inhibits the hydrosilylation reaction used to cure the elastomer system. Here, we report that DL-lactide-a racemic mixture of (R,R)-D-lactide and (S,S)-L-lactide, in which the dilactide molecules are cyclic lactones derived from esterification of two molecules of lactic acid-can be successfully incorporated into and released from addition-cure medical grade silicone elastomer vaginal rings. Following release of lactide from the rings into an aqueous medium, the lactide molecule rapidly hydrolyses to produce only lactic acid. We demonstrate that lactic acid (i) is formed f release of lactide from the rings; (ii) inhibits sperm motility, (iii) inhibits replication of HIV-1 and HSV-2, and (iv) is active against Gardnerella vaginalis (one of the causative organisms responsible for bacterial vaginosis) but not lactobacillus (associated with optimal human vaginal health). The results support the inclusion of lactide as a lactic acid prodrug in next-generation multipurpose contraceptive silicone elastomer vaginal rings.

Journal Title

International journal of pharmaceutics

Volume

684

First Page

126120

Last Page

126120

MeSH Keywords

Silicone Elastomers; Lactic Acid; Delayed-Action Preparations; Contraceptive Devices, Female; Humans; Prodrugs; Female; Vagina; Dioxanes

PubMed ID

40876768

Keywords

Bacterial vaginosis; Herpes simplex virus (HSV); Human immunodeficiency virus (HIV); Hydrolysis; Intravaginal ring; Lactide; Lactobacillus; Multipurpose prevention technology (MPT); Non-hormonal contraception

Comments

This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Publisher's Link: https://www.sciencedirect.com/science/article/pii/S0378517325009573?via%3Dihub

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