2005 ANNUAL SCIENTIFIC MEETING 183 HYDRATION EFFECT ON HUMAN NAIL PERMEABILITY Hemali Gunt and Gerald B. Kasting, Ph.D. College of Pharmacy, University of Cincinnati, Cincinnati, OH Statement of purpose: Onychomycosis is the #1 nail disorder diagnosed and treated by podiatrists and it accounts for up to 50% of nail diseases. Up to 13% of population of the United States is estimated to have dennatophyte onychomycosis. Over the years treatment of onychomycosis has changed from nail avulsion to pharmacotherapy with oral anti-fungals and nail lacquer. A desirable characteristic of a topical antifungal agent in the treabnent of onychomycosis is the ability of the drug to penetrate the keratin of the nail. However, topical treatment alone is generally unable to cure onychomycosis because of insufficient nail plate penetration. The effects of water on keratinized tissues, including horn, wool, hair and stratum comeum are studied to some extent, showing that the mechanical and transport properties are related to water content. While this infonnation is fundamental, literature review shows a paucity of data with respect to human nails. The magnitude of the effect observed in other tissues suggests that hydration may be an important determinate ofungual drug delivery, e.g., for topical treatment of nail dystrophies caused by onychomycosis, nail psoriasis and paronychia. The understanding and knowledge of hydration effects on nail permeability may be useful clinically and cosmetically in topical treabnent of nail disorders. The purpose of this study is to clearly define the effects of hydration on human nail permeability to water, i.e., to quantify transport parameters for water in human nail over a complete range of hydration. Method: We performed vapor phase water sorption-desorption studies at 32°C and 7 different water activities ranging from 15-100% using cadaver finger nails and tritiated water (3H2O) as a probe. Environmental relative humidity was controlled with various concentrations ofH2SO4, NaCl, K2CO3, and LiCl solutions. 1 Human nail samples (3 donors with n=2/donor) free of any adherent tissue were cleaned with a mild detergent solution and dried at 45°C. Dry human nail samples were allowed to sorb over (in vapor phase) tritiated water of radioactive concentration 10 µCi/ml. The nail tissue was weighed periodically to determine whether equilibrium was achieved. At the end of the sorption phase the nail samples were moved periodically over solutions (in vapor phase) with no radioactive compound and the rate of desorption of radioactivity from the nail was measured. Desorption was studied until no radioactivity was detected in the receptor solutions. The vapor phase assembly was replaced between the sorption to desorption phase to eliminate errors resulting from radioactive compound being trapped in the assembly. Radioactivity was measured using liquid scintillation counting. Figure 1: Schematic diagram of the vapor phase sorption-desorption study

184 JOURNAL OF COSMETIC SCIENCE Results and conclusions: The rate and extent of3H2O desorption by the nail samples at each RH was calculated in terms of adsorption volume, v, expressed as (g of water) / (g of dry tissue). Figure 2 shows that the amount of tritiated water desorbed from nail plates decreased with the decrease in water activity. Preliminary analysis of these data using a mathematical solution for desorption of a solute which is uniformly distributed in a homogenous membrane, into a stirred solution with sink conditions, 2 yields diffusivity values from 7.3 X 10-10 cm2/s (for aw= 0.15) to 3.6 X 10- 1 cm2/s (for aw = 1) thus hydration increased diffusivity of water in nail. The desorption rate obtained is a combination of diffusion in the nail tissue and diffusion in vapor phase. A more detailed analysis accounting for the time lag in the vapor phase and tritium exchange with nail proteins is underway. 0.25 • ::I • :! 0.2 � "Cl - 0 en 0.15 .,, ftl E .::: 0.1 ftl -.! 0 :a.as ftl g a a References: 5 10 15 Hour 112 20 Figure 2: Desorption of 3H 2 O from human cadaver nail plates 25 ■Aw-1 □AW-0.89 e Aw-0.8 OAw-0.6 AAWl=OA 6AW-0.27 30 I. Robinson R. A., and Stokes R.H. eds. In Electrolyte solutions, the measurement and interpretation of conductance, chemical potential, and diffusion in solutions of simple electrolytes. Pp 476-492. Butterworth, London (1970). 2. Cooper E.R., and Bemer B. Skin permeability. In Methods in skin research. Pp 407-432. John Wiley and Sons, New York (J 985).