A prodrug strategy for sustained release of lactic acid from silicone elastomer vaginal rings
Document Type
Article (peer-reviewed)
Publication Date
9-2-2025
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.
Recommended Citation
Bashi, Yahya H. Dallal, Xinyu Zhao, Clare F. McCoy, Narender Kumar, Natalia Teleshova, Dolores J. Lamb, José Fernández-Romero, Abigail Meyer, Patrick Barnable, Meropi Aravantinou, Osaretin E. Asowata, Melissa A. White, Alexander J. Travis, Lisa Haddad, Xin Shen, Vicky-Leigh Young, Peter Boyd, and R. Karl Malcolm. 2025. "A prodrug strategy for sustained release of lactic acid from silicone elastomer vaginal rings," International Journal of Pharmaceutics 684: 126120.
DOI
10.1016/j.ijpharm.2025.126120
Language
English
https://doi.org/10.1016/j.ijpharm.2025.126120