Dynamics of HIV neutralization by a microbicide formulation layer: biophysical fundamentals and transport theory.
Topical microbicides are an emerging HIV/AIDS prevention modality. Microbicide biofunctionality requires creation of a chemical-physical barrier against HIV transmission. Barrier effectiveness derives from properties of the active compound and its delivery system, but little is known about how these properties translate into microbicide functionality. We developed a mathematical model simulating biologically relevant transport and HIV-neutralization processes occurring when semen-borne virus interacts with a microbicide delivery vehicle coating epithelium. The model enables analysis of how vehicle-related variables, and anti-HIV compound characteristics, affect microbicide performance. Results suggest HIV neutralization is achievable with postcoital coating thicknesses approximately 100 mum. Increased microbicide concentration and potency hasten viral neutralization and diminish penetration of infectious virus through the coating layer. Durable vehicle structures that restrict viral diffusion could provide significant protection. Our findings demonstrate the need to pair potent active ingredients with well-engineered formulation vehicles, and highlight the importance of the dosage form in microbicide effectiveness. Microbicide formulations can function not only as drug delivery vehicles, but also as physical barriers to viral penetration. Total viral neutralization with 100-mum-thin coating layers supports future microbicide use against HIV transmission. This model can be used as a tool to analyze diverse factors that govern microbicide functionality.
Geonnotti
Anthony R
AR
Department of Biomedical Engineering, Duke University, Durham, NC, USA. anthony.geonnotti@duke.edu
Katz
David F
DF
D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001426:Bacterial Proteins / Q000494:pharmacology; D001692:Biological Transport; D002352:Carrier Proteins / Q000494:pharmacology; D006678:HIV / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D008954:Models, Biological; D014622:Vaginal Creams, Foams, and Jellies; D038301:Virus Inactivation
D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015699:HIV Envelope Protein gp120; D014622:Vaginal Creams, Foams, and Jellies; C107733:cyanovirin N