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Transport of Charged and Uncharged Solutes in Hydrated Human Nail Plate

Baswan, Sudhir

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2014, PhD, University of Cincinnati, Pharmacy: Pharmaceutical Sciences/Biopharmaceutics.
The presence of fungal nail infections such as onychomycosis severely alters nail function and impacts the quality of life. Topical antifungal delivery via iontophoresis is an effective technique which can overcome the efficacy problems associated with currently available oral and topical treatments. Although considerable efforts to develop these devices are under way, little has been done to quantitatively characterize transport of charged and uncharged solutes across the nail plate. The main objective of this research was to characterize the transport process of charged and uncharged solutes in the nail plate using electrochemical methods and a fiber matrix approach, respectively, which would aid in verifying the applicability of the Nernst-Planck model for predicting both passive and iontophoretic transport. Passive diffusion data collected from the literature for uncharged solutes in nail plate was analyzed according to two theories developed to describe the diffusion of uncharged solutes in the corneocyte phase of partially hydrated stratum corneum, which has a keratin fiber volume fraction comparable to that of fully hydrated nail plate. The theories were found to either overpredict (UB/UC) or underpredict (CAU) the permeability of hydrated human nail plate. However, the UB/UC model provided a better fit to passive diffusion data in bovine hoof, another keratin/water system with comparable fiber volume fraction to nail. The comparison suggests that the microstructure of the human nail plate is more complicated than that assumed within the model. Rigorous calculations of solute diffusion in dense keratin fiber arrays and improved microstructure assumptions, as well as better controlled in vitro experiments, are warranted in order to understand the passive transport of solutes in both human nail plate and the corneocyte phase of human stratum corneum.The limiting ionic conductivity of twelve ionic species (7 cations and 5 anions) in nail plate was determined by using in vitro conductivity and electromotive force methods. An inverse power law relationship was observed between the effective ionic diffusivity and solute size for both cations and anions. The effective diffusivity of the cations was found to be 3 –fold higher than the anions of comparable size, consistent with preferential partitioning of the cations into the negatively charge nail plate. The Donnan potential approach was also evaluated to predict the partitioning of charged solutes in the nail plate and was found to be applicable for concentrations ≥ 0.02M. The predictive diffusion model from the electrochemical work was evaluated against selected literature data. Although the model predictions for small solutes (Rs ≤ 3Å) were acceptable, the transport of larger ions was substantially overpredicted. Analytical solutions to the Nernst-Planck equations proposed separately by Planck and Schlogl were also analyzed. Although the Schlogl model overpredicted flux and partitioning at very low concentrations, it did provide a framework for analysis of the charged membrane problem. This research has laid the groundwork for the quantitative description of ion transport in the charged nail plate. We hope it will play a significant role in the development of more robust mathematical models for iontophoretic and passive transport in human nail plate.
Gerald Kasting, Ph.D. (Committee Chair)
Brian Adams, M.D. M.P.H. (Committee Member)
Jinsong Hao, Ph.D. (Committee Member)
Kevin Li, Ph.D. (Committee Member)
R. Randall Wickett, Ph.D. (Committee Member)
243 p.

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Citations

  • Baswan, S. (2014). Transport of Charged and Uncharged Solutes in Hydrated Human Nail Plate [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416233924

    APA Style (7th edition)

  • Baswan, Sudhir. Transport of Charged and Uncharged Solutes in Hydrated Human Nail Plate. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416233924.

    MLA Style (8th edition)

  • Baswan, Sudhir. "Transport of Charged and Uncharged Solutes in Hydrated Human Nail Plate." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416233924

    Chicago Manual of Style (17th edition)