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Systematic investigation of different formulations for drug delivery through the human nail plate "in vitro"

Vejnoviċ, Ivana. Systematic investigation of different formulations for drug delivery through the human nail plate "in vitro". 2010, PhD Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_9217

Abstract

Human nails do not have only protective and decorative role, but can also be considered as an alternative pathway for drug delivery, especially in nail diseases such as onychomycosis or psoriasis. These nail diseases are widely spread in the population, particularly among elderly and immunocompromised patients. Oral therapies are accompanied by systemic side effects and drug interactions, while topical therapies are limited by the low permeation rate through the nail plate. For the successful treatment of nail disease the applied active drug must permeate through the dense keratinized nail plate and reach deeper layers, the nail bed and the nail matrix. Studies conducted on the human skin elucidated its structure, functions, and its permeability for some substances, but very little is known about skin derivate, the nail, and the properties of nail keratin. The purpose of this work is to improve the understanding of physicochemical parameters that influence drug permeation through the nail plate in order to treat not only topical nail diseases but also to consider the possibility to reach systemic circulation and neighboring target sites. The study was divided in two parts, which will be presented as two published articles. In the first part, caffeine has been chosen as hydrophilic model drug for permeability experiments on human cadaver nail samples. Further, a screening of possible permeation enhancers has been fulfilled and hydrophobins, small amphiphilic fungal proteins with an astonishing feature of selfassembling, have been selected as promising enhancers for drug delivery through the human nail plate. In the second part of the study, lipophilic drug terbinafine, which is applied orally in the treatment of onychomycosis, has been tested in permeability experiments from the formulations with and without hydrophobins.
Transport experiments were carried out in Franz diffusion cells across human cadaver nail samples at 32°C under an occlusive effect. Caffeine was applied in a concentration of 2% (w/v) from the water and 20% (v/v) ethanol/water solutions and it was detected by UV spectrophotometer. Duration of permeability studies with caffeine was six days. Terbinafine was applied in a concentration of 10% (w/v) from the 60% (v/v) ethanol/water solutions and it was detected by HPLC. Permeability experiments with terbinafine lasted 10 days. Characterization of the nail samples and applied formulations was maintained throughout the study in order to illuminate examined absorption processes. To detect amount of a drug remained in the nail after experiment, milling test has been performed.
Identified potential enhancers for drug delivery through the human nail plate were methanol, dimethyl sulfoxide (DMSO), and hydrophobins. Methanol and DMSO induced irreversible structural changes in nail samples, while hydrophobins in most of the cases formed a film layer on the nail surface acting not only as enhancers but as protectors, too. Addition of 20% (v/v) ethanol in the formulations did not influence negatively the hydration of the nail and therefore the permeability coefficient. Among three different tested hydrophobins in the formulations with terbinafine, hydrophobin B increased permeation rate 13.05-fold, which assorted it in the list of substances able to augment drug delivery through the nail plate. Although a hydrophilic drug with lower molecular weight compared to terbinafine, caffeine reservoir in the nail plate samples was detected to be lower than terbinafine reservoir, which was influenced by the duration of experiment and which supported a theory that terbinafine has an affinity towards keratin in the nail plate. The question: Can we increase permeation rate even more and enable substances with different chemical and physical properties to permeate through the death keratinized cells of the nail plate, requires further investigations. Finally, an amount of drug which would be detected in the blood should be estimated in vivo.
Advisors:Hamburger, Matthias Otto
Committee Members:Betz, Gabriele and Sakr, Adel
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Biologie (Hamburger)
Item Type:Thesis
Thesis no:9217
Bibsysno:Link to catalogue
Number of Pages:123 S.
Language:English
Identification Number:
Last Modified:30 Jun 2016 10:41
Deposited On:21 Jan 2011 11:23

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