A prodrug strategy for sustained release of lactic acid from silicone elastomer vaginal rings
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".