Transient spreading and swelling behavior of a gel deploying an anti-HIV topical microbicide

• Published in: Journal of non-Newtonian fluid mechanics 2012-11, Vol.187-188, p.36-42
• Main Authors: Tasoglu, Savas, Katz, David F., Szeri, Andrew J.
• Format: Article
• Language: English
• Subjects: Anti-HIV microbicide; API; Computational fluid dynamics; Drug delivery systems; Fluid flow; Fluids; Human immunodeficiency virus; Imbibition; Lubrication flow; Mathematical models; Microorganisms; Non Newtonian fluids; Squeezing flow; Swelling
• ISSN: 0377-0257; 1873-2631
• DOI: 10.1016/j.jnnfm.2012.08.008

► We study the elasto-lubrication flow of a Carreau-like fluid. ► This is a model for a microbicide drug delivery vehicle, intended to coat the vagina. ► Mass transfer occurs due to inhomogeneous dilution of the gel by vaginal fluid. ► Local dilution of gel alters local rheological properties. ► A boundary flux model based upon the elevated pressures in cells is implemented. Drug delivery of topical microbicidal molecules against HIV offers promise as a modality to prevent sexual transmission of the virus. Success of any microbicide product depends, in an interactive way, upon its drug (the microbicide active pharmaceutical ingredient, API) and its delivery system (e.g. a gel, film or intravaginal ring). There is a widespread agreement that more effective drug delivery vehicles, as well as better APIs, must be developed to improve the efficacy of microbicide products. Non-Newtonian gels are primary microbicide vehicles, but those to date have been created with limited understanding of how their properties govern their spreading and retention in the vagina, which, in turn, govern successful drug delivery. Here, we apply fundamental fluid mechanical and physicochemical transport theory to help better understand how successful microbicide API delivery depends upon properties of a gel and the vaginal environment. We address several critical components of this complex process, including: elastohydrodynamic flow of the bolus of a non-Newtonian fluid; and mass transfer due to inhomogeneous dilution of the gel by vaginal fluid contacting it along a moving boundary (the locally deforming vaginal epithelial surface). Local dilution of gel alters local rheological properties. We evaluated this experimentally, delineating the way that constitutive parameters of a shear-thinning gel are modified by dilution. We supplement the Reynolds lubrication equation with a mass conservation equation to model diluting fluid movement across the moving vaginal epithelial surface and into the gel bolus. This is a physicochemically complex phenomenon that is not well understood. We implement a boundary flux model based upon the elevated hydrodynamic pressures in the cells. Results show that this model produces fluxes that lie within the range of mean values that have been reported. Further experimental characterization of the vaginal wall is required for a more precise set of parameters and a more sophisticated theoretical treatment of epithelium.