There is a widespread agreement that more effective drug delivery vehicles with more alternatives, as well as better active pharmaceutical ingredients (APIs), must be developed to improve the efficacy of microbicide products. For instance, in tropical regions, films are more appropriate than gels due to better stability of drugs at extremes of moisture and temperature. Here, we apply fundamental fluid mechanical and physicochemical transport theory to help better understand how successful microbicide API delivery depends upon properties of a film and the human reproductive tract environment. Several critical components of successful drug delivery are addressed. Among these are: elastohydrodynamic flow of a dissolved non-Newtonian film; mass transfer due to inhomogeneous dilution of the film by vaginal fluid contacting it along a moving boundary (the locally deforming vaginal epithelial surface); and drug absorption by the epithelium. Local rheological properties of the film are dependent on local volume fraction of the vaginal fluid. We evaluated this experimentally, delineating the way that constitutive parameters of a shear-thinning dissolved film are modified by dilution. To develop the mathematical model, we integrate the Reynolds lubrication equation with a mass conservation equation to model diluting fluid movement across the moving vaginal epithelial surface and into the film. This is a complex physicochemical phenomenon that is not well understood. We explore time- and space-varying boundary flux model based upon osmotic gradients. Results show that the model produces fluxes that are comparable to experimental data. Further experimental characterization of the vaginal wall is required for a more precise set of parameters and a more sophisticated theoretical treatment of epithelium.
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March 2013
Research Article|
March 04 2013
Transient swelling, spreading, and drug delivery by a dissolved anti-HIV microbicide-bearing film
Savas Tasoglu;
Savas Tasoglu
a)
1Department of Mechanical Engineering,
University of California
, Berkeley, California 94720-1740, USA
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Lisa C. Rohan;
Lisa C. Rohan
2Magee-Womens Research Institute,
University of Pittsburgh
, Pittsburgh, Pennsylvania 15213, USA
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David F. Katz;
David F. Katz
3Department of Biomedical Engineering and Department of Obstetrics and Gynecology,
Duke University
, Box 90281, Durham, North Carolina 22708, USA
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Andrew J. Szeri
Andrew J. Szeri
b)
1Department of Mechanical Engineering,
University of California
, Berkeley, California 94720-1740, USA
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a)
Present address: Now a post-doctoral researcher at Harvard-MIT Health Sciences and Technology.
b)
Author to whom correspondence should be addressed. Electronic mail: aszeri@me.berkeley.edu.
Physics of Fluids 25, 031901 (2013)
Article history
Received:
September 01 2012
Accepted:
February 05 2013
Citation
Savas Tasoglu, Lisa C. Rohan, David F. Katz, Andrew J. Szeri; Transient swelling, spreading, and drug delivery by a dissolved anti-HIV microbicide-bearing film. Physics of Fluids 1 March 2013; 25 (3): 031901. https://doi.org/10.1063/1.4793598
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