Compartmental transport model of microbicide delivery by an intravaginal ring.

Published

Journal Article

Topical antimicrobials, or microbicides, are being developed to prevent HIV transmission through local, mucosal delivery of antiviral compounds. While hydrogel vehicles deliver the majority of current microbicide products, intravaginal rings (IVRs) are an alternative microbicide modality in preclinical development. IVRs provide a long-term dosing alternative to hydrogel use, and might provide improved user adherence. IVR efficacy requires sustained delivery of antiviral compounds to the entire vaginal compartment. A two-dimensional, compartmental vaginal drug transport model was created to evaluate the delivery of drugs from an intravaginal ring. The model utilized MRI-derived ring geometry and location, experimentally defined ring fluxes and vaginal fluid velocities, and biophysically relevant transport theory. Model outputs indicated the presence of potentially inhibitory concentrations of antiviral compounds along the entire vaginal canal within 24 h following IVR insertion. Distributions of inhibitory concentrations of antiviral compounds were substantially influenced by vaginal fluid flow and production, while showing little change due to changes in diffusion coefficients or ring fluxes. Additionally, model results were predictive of in vivo concentrations obtained in clinical trials. Overall, this analysis initiates a mechanistic computational framework, heretofore missing, to understand and evaluate the potential of IVRs for effective delivery of antiviral compounds.

Full Text

Duke Authors

Cited Authors

  • Geonnotti, AR; Katz, DF

Published Date

  • August 2010

Published In

Volume / Issue

  • 99 / 8

Start / End Page

  • 3514 - 3521

PubMed ID

  • 20222027

Pubmed Central ID

  • 20222027

Electronic International Standard Serial Number (EISSN)

  • 1520-6017

International Standard Serial Number (ISSN)

  • 0022-3549

Digital Object Identifier (DOI)

  • 10.1002/jps.22120

Language

  • eng