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Improving the Mechanistic Understanding of Zinc Pyrithione Bioavailability in Skin through Lateral and Transverse Diffusion Measurements

Rush, Allison K
http://orcid.org/0000-0001-8295-0816
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439281238

Abstract Details

2015, PhD, University of Cincinnati, Pharmacy: Pharmaceutical Sciences/Biopharmaceutics.
Routine use of topical antimicrobial agents has long been considered a prophylactic treatment to mitigate the spread of infection and disease. Intrinsic biocidal activities have already been established for many of these ingredients; however, clinical effectiveness is also determined by the delivery of the bioactive to the therapeutic sites of action. This study evaluates the mass transport of zinc pyrithione (ZnPT), a broad-spectrum antimicrobial agent, within the skin as it relates to topical bioavailability, biocidal efficacy, and dermal risk assessment. Using a novel molecular imaging method, the spatial and temporal distribution of residual ZnPT concentrations on the skin surface, compared to amounts penetrated, was measured. Lateral diffusion coefficients and transverse fluxes were quantified for clinically relevant depositions. Both transport processes are expected to be important determinants of topical bioavailability by modifying the proximity of the biocide to microorganisms localized in the upper stratum corneum layers and hair follicles. Formulation and sebum effects on ZnPT dissolution, molecular speciation and subsequent lateral and transverse diffusion were evaluated. ZnPT depositions at levels below and above the estimated saturation dose in the upper stratum corneum distinguished between diffusion-limited and dissolution rate-limited kinetics. Lateral and transverse transport of [14C] associated with ZnPT were formulation-dependent. The presence of zinc carbonate reduced the solubility and dissociation of ZnPT. This resulted in significant reductions in the lateral diffusivity of ZnPT dosed from water and 1% soap solutions. Lateral transport of ZnPT was unaffected by zinc carbonate when deposited from a 1% body wash solution. Sebum was shown to significantly increase the permeation of ZnPT dosed from aqueous suspensions and also potentiate the lateral transport of reference compounds, caffeine and testosterone, on skin. However, the observed sebum enhancement effect was not observed for the lateral transport of ZnPT. This suggests an additional sebum effect may be specific to ZnPT which could be explained by its propensity to undergo molecular transformations. High lateral to transverse diffusion ratios signify that ZnPT is able to migrate laterally on the skin surface to exert biocidal activity prior to temporal reductions in the topically available concentrations. This research advances our understanding of formulation and sebum effects on the mass transport of ZnPT so that antimicrobial formulations can be optimized to maximize therapeutic effectiveness. We conclude that these results also enhance the characterization of microtransport processes within the stratum corneum lamellae so that computational models can be refined to provide more accurate estimates of lateral and transverse transport.
Gerald Kasting, Ph.D. (Committee Chair)
Edward Smith III (Committee Member)
J. F. Nash, Ph.D. (Committee Member)
Jiukuan Hao, Ph.D. (Committee Member)
Kevin Li, Ph.D. (Committee Member)
R. Randall Wickett, Ph.D. (Committee Member)
170 p.
Pharmaceuticals
topical bioavailability; antimicrobial; radioluminography; stratum corneum; lateral diffusion; transverse diffusion

Recommended Citations

Citations

  • Rush, A. K. (2015). Improving the Mechanistic Understanding of Zinc Pyrithione Bioavailability in Skin through Lateral and Transverse Diffusion Measurements [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439281238

    APA Style (7th edition)

  • Rush, Allison. Improving the Mechanistic Understanding of Zinc Pyrithione Bioavailability in Skin through Lateral and Transverse Diffusion Measurements. 2015. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439281238.

    MLA Style (8th edition)

  • Rush, Allison. "Improving the Mechanistic Understanding of Zinc Pyrithione Bioavailability in Skin through Lateral and Transverse Diffusion Measurements." Doctoral dissertation, University of Cincinnati, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439281238

    Chicago Manual of Style (17th edition)

ucin1439281238
1,648
© 2015, some rights reserved.Creative Commons License Improving the Mechanistic Understanding of Zinc Pyrithione Bioavailability in Skin through Lateral and Transverse Diffusion Measurements by Allison K Rush is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.