A model of transluminal flow of an anti-HIV microbicide vehicle: Combined elastic squeezing and gravitational sliding

Abstract

Elastohydrodynamic lubrication over soft substrates is of importance in a number of biomedical problems: From lubrication of the eye surface by the tear film, to lubrication of joints by synovial fluid, to lubrication between the pleural surfaces that protect the lungs and other organs. Such flows are also important for the drug delivery functions of vehicles for anti-HIV topical microbicides. These are intended to inhibit transmission into vulnerable mucosa, e.g., in the vagina. First generation prototype microbicides have gel vehicles, which spread after insertion and coat luminal surfaces. Effectiveness derives from potency of the active ingredients and completeness and durability of coating. Delivery vehicle rheology, luminal biomechanical properties, and the force due to gravity influence the coating mechanics. We develop a framework for understanding the relative importance of boundary squeezing and body forces on the extent and speed of the coating that results. A single dimensionless number, independent of viscosity, characterizes the relative influences of squeezing and gravitational acceleration on the shape of spreading in the Newtonian case. A second scale, involving viscosity, determines the spreading rate. In the case of a shear-thinning fluid, the Carreau number also plays a role. Numerical solutions were developed for a range of the dimensionless parameter and compared well with asymptotic theory in the limited case where such results can be obtained. Results were interpreted with respect to trade-offs between wall elasticity, longitudinal forces, bolus viscosity, and bolus volume. These provide initial insights of practical value for formulators of gel delivery vehicles for anti-HIV microbicidal formulations.

Zinc Acetate/Carrageenan Gels Exhibit Potent Activity In Vivo against High-Dose Herpes Simplex Virus 2 Vaginal and Rectal Challenge

“…Within the vagina, gels can experience shear rates spanning five orders of magnitude: precoital spreading (shear rates as low as 10 Ϫ3 s Ϫ1 ) to coitusinduced spreading (shear rates as high as 10 2 s Ϫ1 ) (28,46). The biomechanics of gel spreading and retention depends upon this entire range, in a multivariate and nonlinear way (24,28,46). A single value of viscosity, measured under standardized conditions, can prove valuable in monitoring differences in gel structure and stability (see below).…”

Gendered innovations: harnessing the creative power of sex and gender analysis to discover new ideas and develop new technologies

“…Specifically, Szeri's lab developed a vaginal gel to deliver microbicides. The physics of the problem is complex: the gel needs to coat the vagina completely and not fall out with the pull of gravity (Szeri et al 2008). These gels can also deliver birth control, if desired.…”

The effects of inhomogeneous boundary dilution on the coating flow of an anti-HIV microbicide vehicle

“…In the method introduced here, we supplement our elastohydrodynamic lubrication model 18 with a convectivediffusive transport equation to account for boundary dilution that is inhomogeneous throughout the diluted, nonNewtonian fluid. In this process, flow of the fluid-in our focus, a gel-is driven by a transversal force (e.g., wall compliance).…”

“…[14][15][16] Those initial studies are instructive in developing a physical understanding of the mechanisms of intravaginal vehicle deployment flows. The second generation model developed by Szeri et al 18 involves simultaneous effects of a longitudinally directed force along the vaginal canal, e.g., gravity, and transversely directed elastic epithelial squeezing, in a lubrication flow analysis. Both Newtonian and non-Newtonian fluids (Carreau constitutive model) were considered.…”