Speaker
Description
An alternative to daily or on-demand methods (pills/gels), intravaginal rings (IVRs) provide long-term, topical drug delivery for contraception, HIV prophylaxis, and hormone therapy. Current IVR designs are based on empirical interpretations of in vitro and in vivo experiments in animals and humans. We developed a deterministic mathematical model of IVR-based drug delivery, to enhance rational IVR design. This multi-compartmental model is a set of coupled PDEs and ODEs embodying conservation of mass that predicts drug diffusion across the ring and into target compartments in the female reproductive tract – vaginal fluid, epithelium, stroma, and bloodstream. Model parameters specify designer-controlled IVR (e.g. ring size, drug properties, initial drug load) and host (e.g. anatomy, histology, drug-cell interactions) characteristics. IVR parameter estimation uses a simplified one compartment model, fit to in-vitro release-into-sink data. We created scaling rules to connect ring designs and experimental data across animal and human trials. This equates/scales biologically relevant model outputs by conserving volume- and time-averaged drug concentration in target regions like the stroma . MCMC simulations captured sensitivity of model outputs to varying IVR sizes, drug loads, and biological variations within/across species. This method is robust to target Islatravir (anti-HIV) drug delivery, and is a step toward comprehensive pharmacokinetic modeling and scaling for diverse IVRs.
