Advanced search
Publication Cover
Expert Opinion on Drug Delivery Volume 5, 2008 - Issue 11
Submit an article Journal homepage
860
Views
105
CrossRef citations to date
0
Altmetric
Review

Enhancing the nail permeability of topically applied drugs

Sudaxshina Murdan University of London, The School of Pharmacy, Department of Pharmaceutics, 29 – 39 Brunswick Square, London, WC1N 1AX, UK +44 20 7753 5810; +44 20 7753 5942; [email protected]
Pages 1267-1282 | Published online: 01 Nov 2008

Bibliography

  • Gupchup GV, Zatz JL. Structural characteristics and permeability properties of the human nail: a review. J Cosmet Sci 1999;50:363-85
  • Murdan S, Drug delivery to the nail following topical application. Int J Pharm 2002;236:1-26
  • Sun Y, Liu JC, Wang JCT, De Doncker P. Nail penetration. Focus on topical delivery of antifungal drugs for onychomycosis treatment. In: Bronaugh, RL, Maibach, HI, Editors. Percutaneous absorption. Drugs–Cosmetics–Mechanisms–Methodology. New York: Marcel Dekker Inc., 1999;759-87
  • Murdan S. 1st meeting on topical drug delivery to the nail. Meeting abstract. Expert Opin Drug Deliv 2007;4:453-5
  • Halmy K. Experience with nail lacquers containing amorolfine 5% and ciclopirox 8% in patients with onychomycosis. J Am Acad Dermatol Suppl 2005;S150:P1821
  • NanoBio Corporation announces positive phase 1 clinical results for topical treatment for onychomycosis, available at http://www.nanobio.com/News/NB-002_Phase1_Results.html [Last accessed 29 April 2008]
  • Van Hoogdalem EJ, Van den Hoven WE, Terpstra IJ, et al. Nail penetration of the antifungal agent oxiconazole after repeated topical application in healthy volunteers, and the effect of acetylcysteine. Eur J Pharm Sci 1997;5:119-27
  • Fleckman P. Basic science of the nail unit, In: Scher, R.K., Daniel, C.R., Editors, Nails: Therapy, Diagnosis, Surgery. Philadelphia: WB Saunders, 1997;37-54
  • Zaias N. The nail in Health and Disease, Connecticut: Appleton and Lange, 1990
  • Jiaravuthisan MM, Sasseville D, Vender RB, et al. Psoriasis of the nail: anatomy, pathology, clinical presentation, and a review of the literature on therapy. J Am Acad Dermatol 2007;57:1-27
  • De Berker D, Forslind B. The structure and properties of nails and periungual tissues. In: Forslind B, Linberg M, Norlén L, Editors. Skin, hair and nails, Structure and Function, New York: Marcel Dekker; 2004:409-64
  • Rich P, Scher RK. An Atlas of Diseases of the Nail. London: Parthenon, 2002
  • Achten G, Andre J, Laporte M. Nails in light and electron microscopy. Semin Dermatol 1991;10:54-64
  • Jemec GBE, Serup J. Ultrasound structure of the human nail plate. Arch Dermatol 1989;125:643-6
  • Wortsman X, GBE Jemec GBE. Ultrasound imaging of nails. Dermatol Clin 2006;24:323-8
  • Jarrett A, Spearman RIC. The histochemistry of the human nail. Arch Derm 1966;94:652-7
  • Ghannoum MA, Hajjeh RA, Scher R, et al. A large-scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns. J Am Acad Dermatol 2000;43:641-8
  • Gupta AK, Shear NH. Onychomycosis: going for cure. Can Fam Physician 1997;43:299-305
  • Daniel CR. The diagnosis of nail fungal infection. Arch Dermatol 1991;127:1566-7
  • Scher RK. Onychomycosis: a significant medical disorder. J Am Acad Dermatol 1996;35:S2-5
  • Cohen PR, Scher RK. Topical and surgical treatment of onychomycosis. J Am Acad Dermatol 1994;31:S74-7
  • Midgley G, Moore MK, Cook JC. Mycology of nail disorders. J Am Acad Dermatol 1994;31:S68-74
  • Baran R, Gupta AK, Piérard GE. Pharmacotherapy of onychomycosis. Expert Opin Pharmacother 2005;6:609-23
  • Baran R, Hay RJ, Garduno JI. Review of antifungal therapy and the severity index for assessing onychomycosis: Part I. J Dermatol Treat 2008;19:72-81
  • Claveau J, Vender RB, Gupta AK. Multitherapy approach to onychomycosis therapy. J Cutan Med Surg 2006;10:S44-7
  • Bristow IR, Baran R. Topical and oral combination therapy for toenail onychomycosis – an updated review. J Am Podiatr Med Assoc 2006;96:116-9
  • Tosti A, Piraccini BM, Stinchi C, Colombo MD. Relapses of onychomycosis after successful treatment with systemic antifungals: a three-year follow-up. Dermatology 1998;197:162-6
  • Arrese JE, Piérard GE. Treatment failures and relapses in onychomycosis: a stubborn clinical problem. Dermatology 2003;207:255-60
  • Samman PD, Fenton DA. The Nails in Disease. London: Butterworth-Heinemann Ltd., 1994
  • De Jong EM, Seegers BA, Gulinck MK, et al. Psoriasis of the nails associated with disability in a large number of patients: results of a recent interview with 1, 728 patients. Dermatology 1996;193:300-3
  • Lawry M. Biological therapy and nail psoriasis. Derm Ther 2007;20:60-7
  • Mertin D, Lippold BC. In vitro permeability of the human nail and of a keratin membrane from bovine hooves: prediction of the penetration rate of antimycotics through the nail plate and their efficiency. J Pharm Pharmacol 1997;49:866-72
  • Kobayashi Y, Komatsu T, Sumi M, et al. In vitro permeation of several drugs through the human nail plate: relationship between physicochemical properties and nail permeability of drugs. Eur J Pharm Sci 2004;21:471-7
  • Walters KA, Flynn GL, Marvel JR. Physicochemical characterisation of the human nail: permeation pattern for water and the homologous alcohols and differences with respect to the stratum corneum. J Pharm Pharmacol 1983;35:28-33
  • Mertin D, Lippold BC. In vitro permeability of the human nail and of a keratin membrane from bovine hooves: influence of the partition coefficient octanol/water and the water solubility of drugs on their permeability and maximum flux. J Pharm Pharmacol 1997;49:30-4
  • Soong, MH. Transport properties of drugs and model compounds across the human nail, PhD dissertation, University of Minnesota, 1991
  • Marshall RC. Characterisation of the proteins of human hair and nail by electrophoresis. J Invest Dermatol 1983;80:519-24
  • Walters KA, Flynn GL, Marvel JR. Penetration of the human nail plate: the effects of vehicle pH on the permeation of miconazole, J Pharm Pharmacol 1985;37:498-9
  • Roberts DT, Evans EG. Subungual dermatophytoma complicating dermatophyte onychomycosis. Br J Dermatol 1998;138:189-90
  • Kobayashi Y, Miyamoto M, Sugibayashi K, Morimoto, Y. Drug permeation through the three layers of the human nail plate. J Pharm Pharmacol 1999;51:271-8
  • Pittrof F, Gerhards J, Erni W, Klecak G. Loceryl( nail lacquer – realisation of a new galenical approach to onychomycosis therapy. Clin Exp Dermatol 1992;17(Suppl 1):26-8
  • Lauharanta J. Comparative efficacy and safety of amorolfine nail lacquer 2-percent versus 5-percent once weekly. Clin Exp Dermatol 1992;17:41-3
  • Hargreaves GK. The treatment of onychomycosis with griseofulvin. Br J Dermatol 1960;72:358-64
  • Fukuda T, Shiohara T. Topical treatment of onychomycosis with an electrically driven high-speed grinder. Jpn J Dermatol 2001;111:37-42
  • Kishimoto K. Evaluation of a nail grinding system using an electronic high-speed dental teeth grinder in patients with onychomycosis. Jpn J Dermatol 2005;115:1035-40
  • Sumikawa M, Egawa T, Honda I, et al. Effects of foot care intervention including nail drilling combined with topical antifungal application in diabetic patients with onychomycosis. J Dermatol 2007;34:456-64
  • Repka MA, O'Haver J, See CH, et al. Nail morphology studies as assessments for onychomycosis treatment modalities. Int J Pharm 2002;245:25-36
  • Repka MA, Mididoddi PK, Stodghill SP. Influence of human nail etching for the assessment of topical onychomycosis therapies. Int J Pharm 2004;282:95-106
  • Neev J, Nelson JS, Critelli M, et al. Ablation of human nail by pulsed lasers. Lasers Surg Med 1997;21:186-92
  • Pathformer: better than a hot paper clip, available from http://medgadget.com/archives/2006/06/pathformer_bett.html [Last accessed 29 April 2008]
  • Boker A, Cioccon D, Kimball A. A randomised, double-blind, placebo-controlled, pilot study of 1% terbinafine cream applied twice daily and delivered via nail plate microporation for the treatment of subungual toenail onychomycosis. J Am Acad Dermatol 2007;56:AB114
  • Ciocon D, Gowrishankar TR, Herndon T, Kimball AB. How low should you go: novel device for nail trephination. Dermatol Surg 2006;32:828-33
  • Transdermal and transungual microconduits, available from http://carlislescientific.com/news.html [Last accessed 03 July 2008]
  • Mididoddi P, Upadhye S, Raymond C, et al. Influence of etching and ultrasound on the permeability of ciclopirox through the human nail. AAPS J 2006;8(S2):R6114
  • Torkar A, Kristl J, Murdan S. Low-frequency ultrasound to enhance topical drug delivery to the nail. AAPS J 2007;9(S2)T3221
  • Mitragotri S, Kost J. Low-frequency sonophoresis – a review. Adv Drug Del Rev 2004;56:589-601
  • Murthy SN, Wiskirchen DE, Bowers CP. Iontophoretic drug delivery across human nail. J Pharm Sci 2007;96:305-11
  • Murthy SN, Waddell DC, Shivakumar HN, et al. Iontophoretic permselective property of human nail. J Dermatol Sci 2007;46:150-2
  • Dutet J, Delgado-Charro MB. Iontophoretic penetration of fluorescein into the nail plate. Proceedings of the 8th annual meeting of Skin Forum; London, 25 – 26 June 2008
  • Ramaswamy C, Kim H, Friden P, Murdan S. Iontophoresis to enhance topical delivery of terbinafine to the nail. AAPS J 2007;9(S2):T3086 poster available from: http://www.scienceposters-online.net/download/?poster_id=126 Accessed 26 September 2008
  • Hao J, Li SK. Transungual iontophoretic transport of polar neutral and positively charged model permeants: effects of electrophoresis and electroosmosis. J Pharm Sci 2008;97:893-905
  • Hao J, Li SK. Mechanistic study of electroosmotic transport across hydrated nail plates: effects of pH and ionic strength. J Pharm Sci 2008;3 April [Epub ahead of print]
  • Hao J, Smith KA, Li SK. Chemical method to enhance transungual transport and iontophoresis efficiency. Int J Pharm 2008;357:61-9
  • Ramaswamy C, Kim H, Friden P, Murdan S. Iontophoresis to enhance topical delivery of terbinafine to the nail. Proceedings of the 8th annual meeting of Skin Forum; London, 2007
  • Dutet J, Delgado-Charro. Transport numbers during trans-ungual iontophoresis. Proceedings of the 9th annual meeting of Skin Forum; London, 2008
  • Stuttgen G, Bauer E. Bioavailability, skin- and nail-penetration of topically applied antimycotics. Mycosen 1982;25:74-80
  • Kligman AM. Topical pharmacology and toxicology of dimethyl sulfoxide. J Am Med Assoc 1965;193:796-804
  • Wang JCT, Sun Y. Human nail and its topical treatment: brief review of current research and development of topical antifungal drug delivery for onychomycosis treatment. J Cosmet Sci 1998;71-76
  • Malhotra GG, Zatz JL. Investigation of nail permeation enhancement by chemical modification using water as a probe. J Pharm Sci 2002;91: 312-23
  • Sun Y, Liu JC, Kimbleton E, Wang J. Antifungal treatment of nails. US patent 5696164, 1997
  • Kobayashi Y, Miyamoto M, Sugibayashi K, Morimoto Y. Enhancing effect of N-acetyl-L-cysteine or 2-mercaptoethanol on the in vitro permeation of 5-fluorouracil or tolnaftate through the human nail plate. Chem Pharm Bull 1998;46:1797-802
  • Khengar RH, Jones SA, Turner RB, et al. Nail swelling as a pre-formulation screen for the selection and optimisation of ungual penetration enhancers. Pharm Res 2007;24:2207-12
  • Stricks W, Kolthoff IM. Equilibrium constants of the reactions of sulfite with cystine and with dithiodiglycolic acid. J Am Chem Soc 1951;73:4569-74
  • Ng Y, Mohorcic M, Torkar A, et al. Sodium sulphite – a potential onycheal enhancer to increase the topical drug delivery to the nail. AAPS J 2007;9(S2):T3181
  • Khengar RH, Jones SA, Brown MB. The use of a novel ungual penetration enhancing technology, MedNail to demonstrate that disulphide bond disruption in the nail increases the permeability of three antifungal agents. Proc Skin Forum 2008, London, 25-6 June
  • Quintanar-Guerrero D, Ganem-Quintanar A, Tapia-Olguin P, et al. The effect of keratolytic agents on the permeability of three imidazole antimycotic drugs through the human nail. Drug Dev Ind Pharm 1998;24:685-90
  • Baran R, Coquard F. Combination of fluconazole and urea in a nail lacquer for treating onychomycosis. J Dermatolog Treat 2005;16:52-5
  • Farber EM, South DA. Urea ointment in the non-surgical avulsion of nail dystrophies. Cutis 1978;22:689-92
  • Baran R, Tosti A. Chemical avulsion with urea nail lacquer. J Dermatol Treat 2002;13:161-4
  • Walters KA, Flynn GL, Marvel JR. Physicochemical characterisation of the human nail: solvent effects on the permeation of homologous alcohols. J Pharm Pharmacol 1985;37:771-5
  • Mertin D, Lippold BC. In vitro permeability of the human nail and of a keratin membrane from bovine hooves: penetration of chloramphenicol from lipophilic vehicles and a nail lacquer. J Pharm Pharmacol 1997;49:241-5
  • Gunt BH, Kasting GB. Effect of hydration on the permeation of ketoconazole through human nail plate in vitro Eur J Pharm Sci 2007;32:254-60
  • Gunt HB, Miller MA, Kasting GB. Water diffusivity in human nail plate. J Pharm Sci 2007;96:3352-62
  • Mohorcic M, Torkar A, Friedrich J, et al. An investigation into keratinolytic enzymes to enhance ungual drug delivery, Int J Pharm 2007;332:196-201
  • Mididoddi PK, Prodduturi S, Repka MA. Influence of tartaric acid on the bioadhesion and mechanical properties of hot-melt extruded hydroxypropyl cellulose films for the human nail. Drug Dev Indus Pharm 2006;32:1059-66
  • Mididoddi PK, Repka MA. Characterization of hot-melt extruded drug delivery systems for onychomycosis. Eur J Pharm Biopharm 2007;66:95-105
  • Trey SM, Wicks DA, Mididoddi PK, Repka MA. Delivery of itraconazole from extruded HPC films. Drug Dev Indus Pharm 2007;33:727-35
  • Myoung Y, Choi HK. Permeation of ciclopirox across porcine hoof membrane: effect of pressure sensitive adhesives and vehicles. Eur J Pharm Sci 2003;20:319-25
  • Donnelly RF, McCarron PA, Lightowler JM, Woolfson AD. Bioadhesive patch-based delivery of 5-aminolevulinic acid to the nail for photodynamic therapy of onychomycosis. J Control Rel 2005;103:381-92
  • Susilo R, Korting HC, Greb W, Strauss UP. Nail penetration of sertaconazole with a sertaconazole-containing nail patch formulation. Am J Clin Dermatol 2006;7:259-62
  • Dubini F, Bellotti MG, Frangi A, et al. In vitro antimycotic activity and nail permeation models of a piroctone olamine (Octopirox) containing transungual water soluble technology. Arzneimittel Forschung Drug Res 2005;55:478-83
  • Monti D, Saccomani L, Chetoni P, et al. In vitro transungual permeation of ciclopirox from a hydroxypropyl chitosan-based, water-soluble nail lacquer. Drug Dev Indus Pharm 2005;31:11-7
  • Hui XY, Chan TCK, Barbadillo S, et al. Enhanced econazole penetration into human nail by 2-n-nonyl-1,3-dioxolane. J Pharm Sci 2003;92:142-8
  • Spruit D. Effect of nail polish on the hydration of the fingernail. Am Cosmetics Perfumery 1972;87:57-8
  • Murdan S, Hinsu D, Guimier M. A few aspects of transonychial water loss (TOWL): inter-individual, and intra-individual inter-finger, inter-hand and inter-day variabilities, and the influence of nail plate hydration, filing and varnish. Eur J Pharm Biopharm 2008;published online 6 June 2008
  • Marty JP. Amorolfine nail lacquer: a novel formulation, J Eur Acad Dermatol Venereol 1995;4(Suppl 1)S17-21
  • Flagothier C, Piérard-Franchimont C, Piérard GE. New insights into the effect of amorolfine nail lacquer. Mycoses 2005;48:91-4
  • Marty JPL, Lambert J, Jackel A, Adjadj L. Treatment costs of three nail lacquers used in onychomycosis. J Dermatol Treatment 2005;16:299-307
  • Brenner MA, Harkless LB, Mendicino RW, Page JC. Ciclopirox 8% nail lacquer topical solution for the treatment of onychomycosis in patients with diabetes: a multicenter, open-label study. J Am Podiatr Med Assoc 2007;97:195-202
  • Baran R, Sigurgeirsson B, de Berker D, et al. A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement. Br J Dermatol 2007;157:149-57
  • Gupta A, Mo YJ, Lu M. A randomized, controlled, dose-ranging study to assess the efficacy and safety of terbinafine HCl nail lacquer for onychomycosis. J Am Acad Dermatol 2006;54(Suppl. S)AB148
  • Chan TC, Czarniecki C, Burrows W, et al. EcoNail (TM) (5% econazole plus 18% SEPA (R) nail lacquer in patients with severe onychomycosis: safety, local tolerability, and systemic exposure. J Invest Dermatol 2005;125:A4-A4926;Article no. 926
  • Regana MS, Ezquerra GM, Millet PU, Mateos FL. Treatment of nail psoriasis with 8% clobetasol nail lacquer: positive experience in 10 patients. J Eur Acad Dermatol Venereol 2005;19:573-7
  • Murdan S. Nail varnish as a drug delivery vehicle. The Drug Delivery Companies Report, 2004; Spring/Summer: 40-42
  • Barak O, Loo DS. AN-2690, a novel antifungal for the topical treatment of onychomycosis. Curr Opin Investig Drugs 2007;8:662-8
  • Hui X, Baker SJ, Wester RC, et al. In vitro penetration of a novel oxaborole antifungal (AN2690) into the human nail plate. J Pharm Sci 2007;96:2622-31
  • Osborne CS, Leitner I, Favre B, Ryder NS. Antifungal drug response in an in vitro model of dermatophyte nail infection. Med Mycol 2004;42:159-63
  • Lenn J, Chern W, Buchta R, et al. A multi-model approach for the evaluation of topical antifungal agents and formulations for the treatment of onychomycosis, Focus on Fungal Infections 17, San Diego, CA, 7-9th March 2007, poster available from: http://www.medpharm.co.uk/news/documents/2007FocusAntifungal_posterl.pdf, Last accessed 02/07/08
  • Meng W, Li HY, Ashbee R, et al. An investigation into correlations between onycheal antifungal drug flux and resulting fungal inhibition in in vitro assays. Proc Skin Forum 2008, London, 25-6 June
  • Arrese JE, Pierard-Franchimont C, Pierard GE. A plea to bridge the gap between antifungals and the management of onychomycosis. Current opinion Am J Clin Dermatol 2001;2:281-4
  • Path Scientific-Trandermal and Transungual Drug Delivery. http://www.pathscientific.com/technology.ps.html

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.