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Review Article

Insights into drug delivery across the nail plate barrier

, &
Pages 769-789 | Received 03 Apr 2014, Accepted 25 May 2014, Published online: 25 Jun 2014

References

  • Barrett JR, Brennan JJ, Patton TP. Formulation and method for the Treatment of fungal 1. Nail infections. US Patent 2010; US 0098645 A1
  • Murdan S. Enhancing the nail permeability of topically applied drugs. Expert Opin Drug Deliv 2008;5:1–16
  • de Berker D. Management of psoriatic nail disease. Semin Cutan Med Surg 2009;28:39–43
  • Hui X, Chan TC, Barbadillo S, et al. Enhanced econazole 4. Penetration into human nail by 2-n-nonyl-1,3-dioxolane. J Pharm Sci 2003;92:142–8
  • 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
  • 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
  • Mididoddi PK, Repka MA. Characterization of hot-melt extruded drug delivery systems for onychomycosis. Eur J Pharm Biopharm 2007;66:95–105
  • 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
  • Warshaw EM, St Clair KR. Prevention of onychomycosis reinfection for patients with complete cure of all 10 toenails: results of a double-blind, placebo-controlled, pilot study of prophylactic miconazole powder 2%. J Am Acad Dermatol 2005;53:717–20
  • Avner S, Nir N, Henri T. Combination of oral terbinafine and topical ciclopirox compared to oral terbinafine for the treatment of onychomycosis. J Dermatolog Treat 2005;16:327–30
  • Nair AB, Kim HD, Davis SP, et al. An ex vivo toe model used to assess applicators for the iontophoretic ungual delivery of terbinafine. Pharm Res 2009;26:2194–201
  • Shivakumar HN, Vaka SRK, Madhav NV, et al. Bilayered nail lacquer of terbinafine hydrochloride for treatment of onychomycosis. J Pharm Sci 2010;99:4267–76
  • Hui X, Wester RC, Barbadillo S, et al. Ciclopirox delivery into the human nail plate. J Pharm Sci 2004;93:2545–8
  • Murdan S. Drug delivery to the nail following topical application. Int J Pharm 2002;236:1–26
  • Achten G, Andre J, Laporte M. Nails in light and electron microscopy. Semin Dermatol 1991;10:54–64
  • 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
  • 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
  • Lynch MH, O'Guin WM, Hardy C, et al. Acidic and basic hair/nail (“hard”) keratins: their colocalization in upper cortical and cuticle cells of the human hair follicle and their relationship to “soft” keratins. J Cell Biol 1986;103:2593–606
  • Garson JC, Baltenneck F, Leroy F, Riekel C, Muller M. Histological structure of human nail as studied by synchrotron X-ray microdiffraction. Cell Mol Biol 2000;46:1025–34
  • Fleckman P. Basic science of the nail unit. In: Scher RK, Daniel III CR, eds. Nails: therapy, diagnosis, surgery, 2nd ed. Philadelphia (PA): WB Saunders; 1997
  • Baden HP, Goldsmith LA, Fleming B. A comparative study of the physicochemical properties of human keratinized tissues. Biochim Biophys Acta 1973;322:269–78
  • Forslind B. Biophysical studies of the normal nail. Acta Derm Venereol 1970;50:161–8
  • Gniadecka M, Nielsen OF, Christensen DH, Wulf HC. Structure of water, proteins, and lipids in intact human skin, hair and nail. J Invest Dermatol 1998;110:393–8
  • Walters KA, Flynn GL. Permeability characteristics of the human nail plate. Int J Cosmet Sci 1983;5:231–46
  • Zaias N. The nail in health and disease, 2nd ed. New York (NY): Spectrum publications Inc.; 1989
  • Baran R, de Berker DAR, Holzberg M, Thomas L. Baran and Dawber's diseases of the nail and their management, 4th ed. Chichester, UK: Wiley-Blackwell, John Wiley and Son's, Ltd; 2012
  • Achten G, Parent D. The normal and pathologic nail. Int J Dermatol 1983;22:556–65
  • Shivakumar HN, Juluri A, Desai BG, Murthy SN. Ungual and Transungual drug delivery. Drug Dev Ind Pharm 2012;38:901–11
  • Alam G, Singh MP, Singh A, et al. Transungual drug transport: advancement and challenges. J Pharm Res 2012;5:2574–9
  • Nail Diseases and Disorders. Available from: www.hooked-on-nails.com/naildisorders.html [last accessed 25 Dec 2013]
  • 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
  • Kaur R, Kashyap B, Bhalla P. Onychomycosis-epidemiology, diagnosis and management. Ind J Med Micobiol 2008;26:108–16
  • de Berker D. Nails and hairs. Medicine 2009;37:286–90
  • Midgley G, Moore MK, Cook JC, Phan QG. Mycology of nail disorders. J Am Acad Dermatol 1994;31:S68–74
  • Sigurgeirsson B, Steingrimsson O. Risk factors associated with onychomycosis. J Eur Acad Dermatol Venereol 2004;18:48–51
  • Cohen PR, Scher RK. Topical and surgical treatment of onychomycosis. J Am Acad Dermatol 1994;31:S74–7
  • Daniel III CR. The diagnosis of nail fungal infection. Arch Dermatol 1991;127:1566–7
  • Gupta AK, Shear NH. Onychomycosis. Going for cure. Can Fam Physician 1997;43:299–305
  • Scher RK. Onychomycosis: a significant medical disorder. J Am Acad Dermatol 1996;35:S2–5
  • Elewski BE, Charif MA, Daniel III CR. Onychomycosis. In: Scher RK, Daniel CR, eds. Nails: therapy, diagnosis, surgery, 3rd ed. Philadelphia (PA): WB Saunders; 2010
  • Niewerth M, Korting HC. Management of onychomycoses. Drugs 1999;58:283–96
  • Baran R, Gupta AK, Pierard GE. Pharmacotherapy of onychomycosis. Expert Opin Pharmacother 2005;6:609–24
  • 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, Pierard GE. Treatment failures and relapses in onychomycosis: a stubborn clinical problem. Dermatology 2003;207:255–60
  • Tosti A, Piraccini BM. Dermatological diseases. In: Scher RK, Daniel III CR, eds. Nails: therapy, diagnosis, surgery, 3d ed. Philadelphia (PA): WB Saunders; 2005
  • Lawry M. Biological therapy and nail psoriasis. Dermatol Ther 2007;20:60–7
  • Farber EM, South DA. Urea ointment in the non-surgical avulsion of nail dystrophies. Cutis 1978;22:689–92
  • 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 efficacy. 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
  • Higa M, Tanioka A, Miyasaka K. A study of ion permeation across a charged membrane in multicomponent ion systems as a function of membrane charge density. J Memb Sci 1990;49:145–69
  • Higa M, Tanioka A, Miyasaka K. An experimental study of ion permeation in multicomponent ion systems as a function of membrane charge density. J Memb Sci 1991;64:255–62
  • Marshall RC. Characterisation of the proteins of human hair and nail by electrophoresis. J Invest Dermatol 1983;80:519–24
  • 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
  • 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
  • Soong MH. Transport properties of drugs and model compounds across the human nail. [PhD dissertation], University of Minnesota; 1991
  • de Berker D, Mawhinney B, Sviland L. Quantification of regional matrix nail production. Br J Dermatol 1996;134:1083–6
  • Murthy SN, Wiskirchen DE, Bowers CP. Iontophoretic drug delivery across human nail. J Pharm Sci 2007;96:305–11
  • 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
  • Pittrof F, Gerhards J, Erni W, Klecak G. Loceryl nail lacquer-realisation of a new galenical approach to onychomycosis therapy. Clin Exp Dermatol 1992;17:26–8
  • Lauharanta J. Comparative efficacy and safety of amorolfine nail lacquer 2-percent versus 5-percent once weekly. Clin Exp Dermatol 1992;17:41–3
  • Baran R, Hay RJ, Garduno JI. Review of antifungal therapy and the severity index for assessing onychomycosis: Part I. J Dermatolog Treat 2008;19:72–81
  • Di Chiacchio N, Kadunc BV, de Almeida AR, Madeira CL. Nail abrasion. J Cosmet Dermatol 2003;2:150–2
  • Fukuda T, Shiohara T. Topical treatment of onychomycosis with an electrically driven high speed grinder. Jpn J Dermatol 2001;111:37–42
  • Hargreaves GK. The treatment of onychomycosis with griseofulvin. Br J Dermatol 1960;72:358–64
  • 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
  • Hettinger DF, Valinsky MS. Treatment of onychomycosis with nail avulsion and topical ketoconazole. J Am Podiatr Med Assoc 1991;81:28–32
  • Murthy SN, Waddell DC, Shivakumar HN, et al. Iontophoretic permselective property of human nail. J Dermatol Sci 2007;46:150–2
  • Hao J, Li SK. Mechanistic study of electroosmotic transport across hydrated nail plates: effects of pH and ionic strength. J Pharm Sci 2008;97:5186–97
  • Manda P, Sammeta SM, Repka MA, Murthy SN. Iontophoresis across the proximal nail fold to target drugs to the nail matrix. J Pharm Sci 2012;101:2391–97
  • 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
  • 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 Ind Pharm 2006;32:1059–66
  • Neev J, Nelson JS, Critelli M, et al. Ablation of human nail by pulsed lasers. Lasers Surg Med 1997;21:186–92
  • Rothermel E, Apfelberg DB. Carbon dioxide laser use for certain diseases of the toenails. Clin Podiatr Med Surg 1987;4:809–21
  • Salter SA, Ciocon DH, Gowrishankar TR, Kimball AB. Controlled nail trephination for subungual hematoma. Am J Emerg Med 2006;24:875–7
  • Platform technology for minimally invasive medical devices. Available from: www.pathscientific.com [last accessed 12 Jan 2014]
  • Ciocon D, Gowrishankar TR, Herndon T, Kimball AB. How low should you go: novel device for nail trephination. Dermatol Surg 2006;32:828–33
  • Boker A, Ciocon D, Kimbell A. A randomized, 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 trephination. J Am Acad Dermatol 2007;56:AB114
  • 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:R6114
  • Torkar A, Kristl J, Murdan S. Low-frequency ultrasound to enhance topical drug delivery to the nail. AAPS J 2007;9:T3221
  • Mitragotri S, Kost J. Low-frequency sonophoresis – a review. Adv Drug Del Rev 2004;56:589–601
  • Azagury A, Khoury L, Enden G, Kost J. Ultrasound mediated transdermal drug delivery. Adv Drug Del Rev 2014;72:127–43
  • Gunt H, Kasting GB. Hydration effect on human nail permeability. J Cosmet Sci 2006;57:183–4
  • Gunt HB, Kasting GB. Effect of hydration on the permeation of ketoconazole through human nail plate in vitro. Eur J Pharm Sci 2007;32:254–60
  • Karell ML. Laser apparatus for making holes and etchings. US Patent 1999, US 005947956A
  • Maltezos G, Scherer A. Treatment of toenail fungus. US Patent 2007, US 0104664A1
  • 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 Release 2005;103:381–92
  • Malhotra GG, Zatz JL. Investigation of nail permeation enhancement by chemical modification using water as a probe. J Pharm Sci 2002;91:312–23
  • 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
  • Brown MB, Khengar RH, Turner RB, et al. Overcoming the nail barrier: a systematic investigation of ungual chemical penetration enhancement. Int J Pharm 2009;370:61–7
  • 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:T3181
  • 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
  • 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. Proceedings Skin Forum; 2008 Jun 25–26; London
  • Gunt HB, Miller MA, Kasting GB. Water diffusivity in human nail plate. J Pharm Sci 2007;96:3352–62
  • Gradisar H, Friedrich J, Krizaj I, Jerala R. Similarities and specificities of fungal keratinolytic proteases: comparison of keratinases of Paecilomyces marquandii and Doratomyces microsporus to some known proteases. Appl Environ Microbiol 2005;71:3420–6
  • Mohorcic M, Torkar A, Friedrich J, Kristl J, Murdan S. An investigation into keratinolytic enzymes to enhance ungual drug delivery. Int J Pharm 2007;332:196–201
  • Quintanar-Guerrero D, Ganem-Quintanar A, Tapia-Olguín 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
  • Sun Y, Liu J, Wang JCT, De Doncker P. Nail penetration. In: Bronaugh RL, Maibach HI, eds. Percutaneous absorption: drugs-cosmetics-mechanisms-methodology, 3rd ed. New York (NY): Marcel Dekker Inc.; 1999
  • Baran R, Coquard F. Combination of fluconazole and urea in a nail lacquer for treating onychomycosis. J Dermatolog Treat 2005;16:52–5
  • Baran R, Tosti A. Chemical avulsion with urea nail lacquer. J Dermatolog Treat 2002;13:161–4
  • Morganti F, Bramanti E, Solaro R, et al. Thermal and spectroscopic characterization of interactions between 2-nonyl-1,3- dioxolane and stratum corneum components. J Bioactive Compatible Polym 1999;14:162–7
  • Samour CM, Donaruma LG, Daskalakis S, et al. SEPAs, a new class of percutaneous absorption enhancers. Proct Int Symp Controlled Rel Bioact Mat 1989;16:183–4
  • Nair AB, Sammeta SM, Vaka SRK, Murthy SN. A study on the effect of inorganic salts in transungual drug delivery of terbinafine. J Pharm Pharmacol 2009;61:431–7
  • Nair AB, Chakraborty C, Murthy SN. Effect of polyethylene glycols on the trans-ungual delivery of terbinafine. Curr Drug Deliv 2010;7:407–14
  • Murthy SN, Vaka SRK, Sammeta SM, Nair AB. TranScreen-N: method for rapid screening of trans-ungual drug delivery enhancers. J Pharm Sci 2009;98:4264–71
  • Murthy SN, Maibach HI. (2012). Topical nail products and ungual drug delivery. Boca Raton (FL): CRC press
  • Vaka SRK, Murthy SN, O'Haver JH, Repka MA. A platform for predicting and enhancing model drug delivery across the human nail plate. Drug Dev Ind Pharm 2011;37:72–9
  • Vignardet C, Guillaume YC, Friedrich J, Millet J. A first order experimental design to assess soluble proteins released by a new keratinase from Doratomyces microsporus on human substrates. Int J Pharm 1999;191:95–102
  • 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 Ind Pharm 2005;31:11–17
  • 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
  • Smith KA, Hao L, Li SK. Effects of ionic strength on passive and iontophoretic transport of cationic permeant across human nail. Pharm Res 2009;26:1446–55
  • Vejnovic I, Simmler L, Betz G. Investigation of different formulations for drug delivery through the nail plate. Int J Pharm 2010;386:185–94
  • Nair AB, Kim H, Friden P, et al. Transungual iontophoresis of terbinafine for onychomycosis: ex vivo evaluation. J Am Acad Dermatol 2009;60:AB115
  • Xiao P, Zheng X, Imhof RE, et al. Opto-thermal transient emission radiometry (OTTER) to image diffusion in nails in vivo. Int J Pharm 2011;406:111–13
  • Hay RJ, Clayton YM, Moore MK. A comparison of tioconazole 28% nail solution versus base as an adjunct to oral griseofulvin in patients with onychomycosis. Clin Exp Dermatol 1987;12:175–7
  • Hui X, Shainhouse Z, Tanojo H, et al. Enhanced human nail drug delivery: nail inner drug content assayed by new unique method. J Pharm Sci 2002;91:189–95
  • 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
  • Suringa DW. Treatment of superficial onychomycosis with topically applied glutaraldehyde. A preliminary study. Arch Dermatol 1970;102:163–7
  • Marty JL. Amorolfine nail lacquer: a novel formulation. J Eur Acad of Dermatol Venereol 1995;4:S17–21
  • Franz TJ. Absorption of amorolfine through human nail. Dermatology 1992;184:18–20
  • Gupta AK, Fleckman P, Baran R. Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. J Am Acad Dermatol 2000;43:S70–80
  • Polak A. Amorolfine: a review of its mode of action and in vitro and in vivo antifungal activity. J Am Med Assoc South East Asia 1993;9:11–18
  • Obadiah J, Scher R. Nail disorders: unapproved treatments. Clin Dermatol 2002;20:643–8
  • Baden HP. Treatment of distal onychomycosis with avulsion and topical antifungal agents under occlusion. Arch Dermatol 1994;130:558–9
  • Bindra RL, Singh AK, Shawl AS, Kumar S. Anti-fungal herbal formulation for treatment of human nails fungus and process thereof. US Patent 2001; US 6296838 B1
  • Tandel A, Agrawal S, Wankhede S. Transungual permeation of the Voriconazole nail lacquer against Trichophyton rubrum. J Drug Deliv Ther 2012;2:25–33
  • Lusiana, Reichl S, Muller-Goymann CC. Infected nail plate model made of human hair keratin for evaluating the efficacy of different topical antifungal formulations against Trichophyton rubrum in vitro. Eur J Pharm Biopharm 2013;84:599–605
  • Hafeez F, Hui X, Chiang A, et al. Transungual delivery of ketoconazole using novel lacquer formulation. Int J Pharm 2013;456:357–61
  • Nogueiras-Nieto L, Delgado-Charro MB, Otero-Espinar FJ. Thermogelling hydrogels of cyclodextrin/poloxamer polypseudorotaxanes as aqueous-based nail lacquers: application to the delivery of triamcinolone acetonide and ciclopirox olamine. Eur J Pharm Biopharm 2013;83:370–7
  • Tanrıverdi ST, Ozer O. Novel topical formulations of Terbinafine-HCl for treatment of onychomycosis. Eur J Pharm Sci 2013;48:628–36
  • Miron D, Cornelio R, Troleis J, et al. Influence of penetration enhancers and molecular weight in antifungals permeation through bovine hoof membranes and prediction of efficacy in human nails. Eur J Pharm Sci 2014;51:20–5
  • Nimni M. Anti-fungal nail lacquer and method therefor. US Patent 1996; US 005487776 A
  • Sorenson JL, Petersen RV. Composition and method for treating diseased nail. US Patent 1998; US 005840283 A
  • Chaudhari B, Chim MF, Bucks D. Topical formulations for the treatment of nail fungal 135. diseases. US Patent 2000; US 006143794 A
  • Quan D, Ruiz A. Nail compositions and methods for administering same. US Patent 2003; US 006585963 B1
  • Maibach HI, Luo EC, Hsu T. Topical administration of basic antifungal compositions to treat fungal infections of the nails. US Patent 2005; US 006846837 B2
  • Mailland F. Nail restructuring compositions for topical application. US Patent 2006; US 0134039 A1
  • Riley L. Topical formulation for treating fingernails and toenails. US Patent 2007; US 007198794 B1
  • Meyer H. Pharmaceutical and cosmetic formulations for treating fingernails. US Patent 2007; US 0166249 A1
  • Kepka SW, Mo J, Wang H, et al. Antifungal nail coat and method of use. US Patent 2008; US 7462362 B2
  • Kochinke FM, Bright C. Compositions and methods for treating conditions of the nail unit. US Patent 2008; US 0132442 A1
  • Etheredge RW, Goldberg DI, Davis SP, et al. Method and system for treating of onychomycosis with an applicator having gel medicament layer. US Patent 2008; US 0319371 A1
  • Zhang J, Warner KS, Kumar P, Aliyar H. Systems, methods, and formulations for topically treating nail fungal infections and nail psoriasis. US Patent 2009; US 0175945 A1
  • Singh J, Dan M. Topical nail formulation. US Patent 2009; US 0215888 A1
  • Cevc G, Vierl U. Topical terbinafine formulations and methods of administering same for the treatment of fungal infections. US Patent 2010; US 7820720 B2
  • Bailey C. Method and apparatus for improving the appearance of nails affected by onychomycosis through the topical application of highly concentrated or supersaturated boric acid. US Patent 2011; US 0083692 A1
  • Lusiana, Muller-Goymann C. Formulation for nail and nail bed diseases. US Patent 2012; US 0010227 A1
  • Available from www.clinicaltrials.gov [last accessed 07 May 2014]
  • Dutet J, Delgado-Charro MB. Electroosmotic transport of mannitol across human nail during constant current iontophoresis. J Pharm Pharmacol 2010;62:721–9
  • Dutet J, Delgado-Charro MB. Transungual iontophoresis of lithium and sodium: effect of pH and co-ion competition on cationic transport numbers. J Control Release 2010;144:168–74
  • Dutet J, Delgado-Charro MB. In vivo transungual iontophoresis: effect of DC current application on ionic transport and on Transonychial water loss. J Control Release 2009;140:117–25
  • Nogueiras Nieto L, Gomez Amoza JL, Delgado Charro MB, Otero-Espinar FJ. Hydration and N-acetyl-l-cysteine alter the microstructure of human nail and bovine hoof: implications for drug delivery. J Control Release 2011;156:337–44
  • Smith KA, Hao J, Li SK. Influence of pH on transungual passive and iontophoretic transport. J Pharm Sci 2010;99:1955–67
  • Hao J, Smith KA, Li SK. Iontophoretically enhanced ciclopirox delivery into and across human nail plate. J Pharm Sci 2009;98:3608–16
  • Hao J, Smith KA, Li SK. Chemical method to enhance transungual transport and iontophoresis efficiency. Int J Pharm 2008;357:61–9
  • Hao J, Smith KA, Li SK. Time-dependent electrical properties of human nail upon hydration in vivo. J Pharm Sci 2010;99:107–18
  • Smith KA, Hao J, Li SK. Effect of organic solvents on the barrier properties of human nail. J Pharm Sci 2011;100:4244–57

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