Skip to main content

Carriers in the Topical Treatment of Skin Disease

Part of the Handbook of Experimental Pharmacology book series (HEP,volume 197)

Abstract

Topical drug application is less prone to severe systemic side-effects than systemic application. Starting with the liposomes, various types of nanosized and microsized drug carriers have been developed to increase the notoriously low penetration of active agents into the skin, which limits not only the topical therapy of skin disease but also transdermal therapy. Today, liposome- and microsponge-based preparations are approved for dermatomycosis, acne and actinic keratosis. Under investigation are drug carriers such as lipid nanoparticles, polymeric particles, dendrimers, and dendritic-core multi-shell nanotransporters. According to the rapidly increasing research in this field, both in academia and industry, a breakthrough appears likely, once stability problems (nanoparticles) and safety concerns (dendrimers) are overcome. Technical approaches and results of in vitro, ex vivo and in vivo testing are described, taking into account pharmacokinetic, efficacy and safety aspects.

Keywords

  • Skin penetration
  • Cutaneous absorption
  • Drug carriers
  • Liposome
  • Solid lipid nanoparticle
  • Microemulsion
  • Polymer particles

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-642-00477-3_15
  • Chapter length: 34 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   349.00
Price excludes VAT (USA)
  • ISBN: 978-3-642-00477-3
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   449.99
Price excludes VAT (USA)
Hardcover Book
USD   549.99
Price excludes VAT (USA)
Fig. 1
Fig. 2
Fig. 3
Fig. 4

Abbreviations

5-FU:

5-Fluorouracil

API:

Active pharmaceutical ingredient

CAT-1:

4-Trimethyl-ammonium-2,2,6,6-tetramethylpiperidine-1-oxyliodide

CMS:

Core multi-shell (nanotransporters)

CNT:

(Carbo-)nanotubes

CPA:

Cyproterone acetate

FITC:

Fluorescein 5-isothiocyanate

GRAS:

Generally recognised as safe

logP :

Octanol:water partition coefficient

MCT:

Medium chain triglycerides

NLC:

Nanostructured lipid carriers

OECD:

Organisation for Economic Co-operation and Development

PLA:

Polylactic acid

PLGA:

Poly(d,l-lactic-co-glycolic acid)

PASI:

Psoriasis Area and Severity Index

QSPR:

Quantitative structure permeability relationship

SCCP:

Scientific Committee on Consumer Products

SLN:

Solid lipid nanoparticles

TAC:

Triamcinolone acetonide

References

  • Abramovic Z, Sustarsic U, Teskac K, Sentjurc M, Kristl J (2008) Influence of nanosized delivery systems with benzyl nicotinate and penetration enhancers on skin oxygenation. Int J Pharm 359:220–227

    CAS  PubMed  Google Scholar 

  • Akiyama M, Shimizu H (2008) An update on molecular aspects of the non-syndromic ichthyoses. Exp Dermatol 17:373–382

    CAS  PubMed  Google Scholar 

  • Alvarez-Roman R, Barre G, Guy RH, Fessi H (2001) Biodegradable polymer nanocapsules containing a sunscreen agent: preparation and photoprotection. Eur J Pharm Biopharm 52:191–195

    CAS  PubMed  Google Scholar 

  • Alvarez-Roman R, Naik A, Kalia YN, Guy RH, Fessi H (2004a) Enhancement of topical delivery from biodegradable nanoparticles. Pharm Res 21:1818–1825

    CAS  PubMed  Google Scholar 

  • Alvarez-Roman R, Naik A, Kalia YN, Guy RH, Fessi H (2004b) Skin penetration and distribution of polymeric nanoparticles. J Control Release 99:53–62

    CAS  Google Scholar 

  • Anigbogu AN, Williams AC, Barry BW (1996) Permeation characteristics of 8-methoxypsoralen through human skin; relevance to clinical treatment. J Pharm Pharmacol 48:357–366

    CAS  PubMed  Google Scholar 

  • Anton N, Benoit JP, Saulnier P (2008) Design and production of nanoparticles formulated from nano-emulsion templates – a review. J Control Release 128:185–199

    CAS  Google Scholar 

  • Barry BW (2004) Breaching the skin's barrier to drugs. Nature Biotechnol 22:165–167

    CAS  PubMed  Google Scholar 

  • Bashir SJ, Chew AL, Anigbogu A, Dreher F, Maibach HI (2001) Physical and physiological effects of stratum corneum tape stripping. Skin Res Technol 7:40–48

    CAS  PubMed  Google Scholar 

  • Bernard E, Dubois JL, Wepierre J (1997) Importance of sebaceous glands in cutaneous penetration of an antiandrogen: target effect of liposomes. J Pharm Sci 86:573–578

    CAS  PubMed  Google Scholar 

  • Blaschke T, Kankate L, Kramer KD (2007) Structure and dynamics of drug-carrier systems as studied by parelectric spectroscopy. Adv Drug Deliv Rev 59:403–410

    CAS  PubMed  Google Scholar 

  • Blaschke T, Spangenberg T, Dathe M, Mehnert W, Korting HC, Schäfer-Korting M, Kramer KD (in press) Interaction of drug-carrier systems with targets – a study using atomic force microscopy

    Google Scholar 

  • Bouwstra JA, Honeywell-Nguyen PL (2002) Skin structure and mode of action of vesicles. Adv Drug Deliv Rev 54(Suppl 1):S41–55

    CAS  PubMed  Google Scholar 

  • Bouwstra JA, Ponec M (2006) The skin barrier in healthy and diseased state. Biochim Biophys Acta 1758:2080–2095

    CAS  PubMed  Google Scholar 

  • Braem C, Blaschke T, Panek-Minkin G, Herrmann W, Schlupp P, Paepenmüller T, Müller-Goyman C, Mehnert W, Bittl R, Schäfer-Korting M, Kramer KD (2007) Interaction of drug molecules with carrier systems as studied by parelectric spectroscopy and electron spin resonance. J Control Release 119:128–135

    CAS  Google Scholar 

  • Bronaugh RL, Franz TJ (1986) Vehicle effects on percutaneous absorption: in vivo and in vitro comparisons with human skin. Br J Dermatol 115:1–11

    CAS  PubMed  Google Scholar 

  • Bronaugh RL, Stewart RF (1985) Methods for in vitro percutaneous absorption studies IV: the flow-through diffusion cell. J Pharm Sci 74:64–67

    CAS  PubMed  Google Scholar 

  • Cevc G (2004) Lipid vesicles and other colloids as drug carriers on the skin. Adv Drug Deliv Rev 56:675–711

    CAS  PubMed  Google Scholar 

  • Chen H, Chang X, Du D, Liu W, Liu J, Weng T, Yang Y, Xu H, Yang X (2006) Podophyllotoxin-loaded solid lipid nanoparticles for epidermal targeting. J Control Release 110:296–306

    CAS  Google Scholar 

  • Choi MJ, Maibach HI (2005) Role of ceramides in barrier function of healthy and diseased skin. Am J Clin Dermatol 6:215–223

    PubMed  Google Scholar 

  • Date AA, Naik B, Nagarsenker MS (2006) Novel drug delivery systems: potential in improving topical delivery of antiacne agents. Skin Pharmacol Physiol 19:2–16

    CAS  PubMed  Google Scholar 

  • Dayan N, Touitou E (2000) Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes. Biomaterials 21:1879–1885

    CAS  PubMed  Google Scholar 

  • Dreher F, Modjtahedi BS, Modjtahedi SP, Maibach HI (2005) Quantification of stratum corneum removal by adhesive tape stripping by total protein assay in 96-well microplates. Skin Res Technol 11:97–101

    CAS  PubMed  Google Scholar 

  • Dubey V, Mishra D, Dutta T, Nahar M, Saraf DK, Jain NK (2007) Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes. J Control Release 123:148–154

    CAS  Google Scholar 

  • Elsayed MM, Abdallah OY, Naggar VF, Khalafallah NM (2007) Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int J Pharm 332:1–16

    CAS  PubMed  Google Scholar 

  • Fang JY, Hwang TL, Fang CL, Chiu HC (2003) In vitro and in vivo evaluations of the efficacy and safety of skin permeation enhancers using flurbiprofen as a model drug. Int J Pharm 255:153–166

    CAS  PubMed  Google Scholar 

  • Feldmann RJ, Maibach HI (1969) Percutaneous penetration of steroids in man. J Invest Dermatol 52:89–94

    CAS  PubMed  Google Scholar 

  • Fesq H, Lehmann J, Kontny A, Erdmann I, Theiling K, Rother M, Ring J, Cevc G, Abeck D (2003) Improved risk-benefit ratio for topical triamcinolone acetonide in transfersome in comparison with equipotent cream and ointment: a randomized controlled trial. Br J Dermatol 149:611–619

    CAS  PubMed  Google Scholar 

  • Geinoz S, Guy RH, Testa B, Carrupt PA (2004) Quantitative structure-permeation relationships (QSPeRs) to predict skin permeation: a critical evaluation. Pharm Res 21:83–92

    CAS  PubMed  Google Scholar 

  • Gloor M (2004) How do dermatological vehicles influence the horny layer? Skin Pharmacol Physiol 17:267–273

    CAS  PubMed  Google Scholar 

  • Grimes PE (2004) A microsponge formulation of hydroquinone 4% and retinol 0.15% in the treatment of melasma and postinflammatory hyperpigmentation. Cutis 74:362–368

    PubMed  Google Scholar 

  • Haag R, Kratz F (2006) Polymer therapeutics: concepts and applications. Angew Chem (Int Ed) 45:1198–1215

    CAS  Google Scholar 

  • Heard CM, Monk BV, Modley AJ (2003) Binding of primaquine to epidermal membranes and keratin. Int J Pharm 257:237–244

    CAS  PubMed  Google Scholar 

  • Hoffman RM (1998) Topical liposome targeting of dyes, melanins, genes, and proteins selectively to hair follicles. J Drug Target 5:67–74

    CAS  PubMed  Google Scholar 

  • Hu FQ, Yuan H, Zhang HH, Fang M (2002) Preparation of solid lipid nanoparticles with clobetasol propionate by a novel solvent diffusion method in aqueous system and physicochemical characterization. Int J Pharm 239:121–128

    CAS  PubMed  Google Scholar 

  • Hueber F, Schaefer H, Wepierre J (1994) Role of transepidermal and transfollicular routes in percutaneous absorption of steroids: in vitro studies on human skin. Skin Pharmacol 7:237–244

    CAS  PubMed  Google Scholar 

  • Iannuccelli V, Coppi G, Sergi S, Mezzena M, Scalia S (2008) In vivo and in vitro skin permeation of butyl methoxydibenzoylmethane from lipospheres. Skin Pharmacol Physiol 21:30–38

    CAS  PubMed  Google Scholar 

  • Iraji F, Momeni A, Naji SM, Siadat AH (2006) The efficacy of topical cyproterone acetate alcohol lotion versus placebo in the treatment of the mild to moderate acne vulgaris: a double blind study. Dermatol Online J 12:26

    PubMed  Google Scholar 

  • Jacobi U, Gautier J, Sterry W, Lademann J (2005a) Gender-related differences in the physiology of the stratum corneum. Dermatology 211:312–317

    PubMed  Google Scholar 

  • Jacobi U, Weigmann HJ, Ulrich J, Sterry W, Lademann J (2005b) Estimation of the relative stratum corneum amount removed by tape stripping. Skin Res Technol 11:91–96

    CAS  PubMed  Google Scholar 

  • Jain SK, Chourasia MK, Masuriha R, Soni V, Jain A, Jain NK, Gupta Y (2005) Solid lipid nanoparticles bearing flurbiprofen for transdermal delivery. Drug Deliv 12:207–215

    CAS  PubMed  Google Scholar 

  • Jelvehgari M, Siahi-Shadbad MR, Azarmi S, Martin GP, Nokhodchi A (2006) The microsponge delivery system of benzoyl peroxide: preparation, characterization and release studies. Int J Pharm 308:124–132

    CAS  PubMed  Google Scholar 

  • Jenning V, Gysler A, Schäfer-Korting M, Gohla SH (2000a) Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin. Eur J Pharm Biopharm 49:211–218

    CAS  PubMed  Google Scholar 

  • Jenning V, Schäfer-Korting M, Gohla S (2000b) Vitamin A-loaded solid lipid nanoparticles for topical use: drug release properties. J Control Release 66:115–126

    CAS  Google Scholar 

  • Jores K, Haberland A, Wartewig S, Mäder K, Mehnert W (2005) Solid lipid nanoparticles (SLN) and oil-loaded SLN studied by spectrofluorometry and Raman spectroscopy. Pharm Res 22:1887–1897

    CAS  PubMed  Google Scholar 

  • Kalariya M, Padhi BK, Chougule M, Misra A (2005) Clobetasol propionate solid lipid nanoparticles cream for effective treatment of eczema: formulation and clinical implications. Indian J Exp Biol 43:233–240

    CAS  PubMed  Google Scholar 

  • Karande P, Jain A, Mitragotri S (2004) Discovery of transdermal penetration enhancers by high-throughput screening. Nature Biotechnol 22:192–197

    CAS  PubMed  Google Scholar 

  • Katritzky AR, Dobchev DA, Fara DC, Hur E, Tamm K, Kurunczi L, Karelson M, Varnek A, Solov'ev VP (2006) Skin permeation rate as a function of chemical structure. J Med Chem 49:3305–3314

    CAS  PubMed  Google Scholar 

  • Korting HC, Klövekorn W, Klövekorn G, and the Ecosome Collaborative Study Group (1997) Comparative efficacy and tolerability of econazole liposomal gel 1%, branded econazol convetional cream 1% and generic clotrimazole cream 1% in tinea pedis. Clin Drug Invest 14:286–293

    Google Scholar 

  • Korting HC, Patzak U, Schaller M, Maibach HI (1998) A model of human cutaneous candidosis based on reconstructed human epidermis for the light and electron microscopic study of pathogenesis and treatment. J Infect 36:259–267

    CAS  PubMed  Google Scholar 

  • Korting HC, Unholzer A, Schäfer-Korting M, Tausch I, Gassmueller J, Nietsch KH (2002) Different skin thinning potential of equipotent medium-strength glucocorticoids. Skin Pharmacol Appl Skin Physiol 15:85–91

    CAS  PubMed  Google Scholar 

  • Krämer M, Stumbe JF, Türk H, Krause S, Komp A, Delineau L, Prokhorova S, Kautz H, Haag R (2002) pH-responsive molecular nanocarriers based on dendritic core-shell architectures. Angew Chem (Int Ed) 41:4252–4256

    Google Scholar 

  • Kreilgaard M (2002) Influence of microemulsions on cutaneous drug delivery. Adv Drug Deliv Rev 54(Suppl 1):S77–98

    CAS  PubMed  Google Scholar 

  • Kriftner RW (1992) Liposome production: The ethanol injection technique and the development of the first approved liposome dermatic. In: Braun-Falco O, Korting HC, Maibach HI (eds) Griesbach conference liposome dermatics. Springer, Berlin, pp 91–100

    Google Scholar 

  • Küchler S, Radowski MR, Blaschke T, Dathe M, Plendl J, Haag R, Schäfer-Korting M, Kramer KD (2008) Nanoparticles for skin penetration enhancement – a comparison of a dendritic core-multishell-nanotransporter and solid lipid nanoparticles. Eur J Pharm Biopharm 71:243–250

    PubMed  Google Scholar 

  • Lademann J, Richter H, Golz K, Zastrow L, Sterry W, Patzelt A (2008) Influence of microparticles on the homogeneity of distribution of topically applied substances. Skin Pharmacol Physiol 21:274–282

    CAS  PubMed  Google Scholar 

  • Lademann J, Richter H, Teichmann A, Otberg N, Blume-Peytavi U, Luengo J, Weiss B, Schaefer UF, Lehr CM, Wepf R, Sterry W (2007) Nanoparticles – an efficient carrier for drug delivery into the hair follicles. Eur J Pharm Biopharm 66:159–164

    CAS  PubMed  Google Scholar 

  • Lademann J, Rudolph A, Jacobi U, Weigmann HJ, Schaefer H, Sterry W, Meinke M (2004) Influence of nonhomogeneous distribution of topically applied UV filters on sun protection factors. J Biomed Opt 9:1358–1362

    CAS  PubMed  Google Scholar 

  • Lademann J, Weigmann H, Rickmeyer C, Barthelmes H, Schaefer H, Mueller G, Sterry W (1999) Penetration of titanium dioxide microparticles in a sunscreen formulation into the horny layer and the follicular orifice. Skin Pharmacol Appl Skin Physiol 12:247–256

    CAS  PubMed  Google Scholar 

  • Lademann J, Weigmann HJ, Schanzer S, Richter H, Audring H, Antoniou C, Tsikrikas G, Gers-Barlag H, Sterry W (2005) Optical investigations to avoid the disturbing influences of furrows and wrinkles quantifying penetration of drugs and cosmetics into the skin by tape stripping. J Biomed Opt 10:54015

    Google Scholar 

  • Lakshmi PK, Devi GS, Bhaskaran S, Sacchidanand S (2007) Niosomal methotrexate gel in the treatment of localized psoriasis: phase I and phase II studies. Indian J Dermatol Venereol Leprol 73:157–161

    CAS  PubMed  Google Scholar 

  • Lehmann L, Keipert S, Gloor M (2001) Effects of microemulsions on the stratum corneum and hydrocortisone penetration. Eur J Pharm Biopharm 52:129–136

    CAS  PubMed  Google Scholar 

  • Liu J, Hu W, Chen H, Ni Q, Xu H, Yang X (2007) Isotretinoin-loaded solid lipid nanoparticles with skin targeting for topical delivery. Int J Pharm 328:191–195

    CAS  PubMed  Google Scholar 

  • Löffler H, Dreher F, Maibach HI (2004) Stratum corneum adhesive tape stripping: influence of anatomical site, application pressure, duration and removal. Br J Dermatol 151:746–752

    PubMed  Google Scholar 

  • Lombardi Borgia S, Regehly M, Sivaramakrishnan R, Mehnert W, Korting HC, Danker K, Röder B, Kramer KD, Schäfer-Korting M (2005) Lipid nanoparticles for skin penetration enhancement – correlation to drug localization within the particle matrix as determined by fluorescence and parelectric spectroscopy. J Control Release 110:151–163

    CAS  PubMed  Google Scholar 

  • Lombardi Borgia S, Schlupp P, Mehnert W, Schäfer-Korting M (2008) In vitro skin absorption and drug release – a comparison of six commercial prednicarbate preparations for topical use. Eur J Pharm Biopharm 68:380–389

    CAS  PubMed  Google Scholar 

  • Luengo J, Weiss B, Schneider M, Ehlers A, Stracke F, Konig K, Kostka KH, Lehr CM, Schaefer UF (2006) Influence of nanoencapsulation on human skin transport of flufenamic acid. Skin Pharmacol Physiol 19:190–197

    CAS  PubMed  Google Scholar 

  • Majumdar S, Thomas J, Wasdo S, Sloan KB (2007) The effect of water solubility of solutes on their flux through human skin in vitro. Int J Pharm 329:25–36

    CAS  PubMed  Google Scholar 

  • McKenzie AW, Stoughton RB (1962) A method for comparing percutaneous absorption of steroids. Arch Dermatol 86:608–610

    Google Scholar 

  • Mei Z, Chen H, Weng T, Yang Y, Yang X (2003) Solid lipid nanoparticle and microemulsion for topical delivery of triptolide. Eur J Pharm Biopharm 56:189–196

    CAS  PubMed  Google Scholar 

  • Menter A, Vamvakias G, Jorizzo J (2008) One-week treatment with once-daily fluorouracil cream 0.5% in participants with actinic keratoses. Cutis 81:509–516

    PubMed  Google Scholar 

  • Miyazaki S, Takahashi A, Kubo W, Bachynsky J, Loebenberg R (2003) Poly n-butylcyanoacrylate (PNBCA) nanocapsules as a carrier for NSAIDs: in vitro release and in vivo skin penetration. J Pharm Pharm Sci 6:238–245

    PubMed  Google Scholar 

  • Moll KP, Stosser R, Herrmann W, Borchert HH, Utsumi H (2004) In vivo ESR studies on subcutaneously injected multilamellar liposomes in living mice. Pharm Res 21:2017–2024

    CAS  PubMed  Google Scholar 

  • Moser K, Kriwet K, Froehlich C, Naik A, Kalia YN, Guy RH (2001) Permeation enhancement of a highly lipophilic drug using supersaturated systems. J Pharm Sci 90:607–616

    CAS  PubMed  Google Scholar 

  • Moss GP, Dearden JC, Patel H, Cronin MT (2002) Quantitative structure-permeability relationships (QSPRs) for percutaneous absorption. Toxicol In Vitro 16:299–317

    CAS  PubMed  Google Scholar 

  • Müller RH, Petersen RD, Hommoss A, Pardeike J (2007) Nanostructured lipid carriers (NLC) in cosmetic dermal products. Adv Drug Deliv Rev 59:522–530

    PubMed  Google Scholar 

  • Müller RH, Radtke M, Wissing SA (2002) Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev 54(Suppl 1):S131–155

    PubMed  Google Scholar 

  • Müller RH, Rühl D, Runge S, Schulze-Forster K, Mehnert W (1997) Cytotoxicity of solid lipid nanoparticles as a function of the lipid matrix and the surfactant. Pharm Res 14:458–462

    PubMed  Google Scholar 

  • Münster U, Nakamura C, Haberland A, Jores K, Mehnert W, Rummel S, Schaller M, Korting HC, Zouboulis Ch C, Blume-Peytavi U, Schäfer-Korting M (2005) RU 58841-myristate – prodrug development for topical treatment of acne and androgenetic alopecia. Pharmazie 60:8–12

    PubMed  Google Scholar 

  • Mutschler E, Geisslinger G, Kroemer HK, Ruth P, Schäfer-Korting M (2008) Mutschler Arzneimittelwirkungen: Lehrbuch der Pharmakologie und Toxikologie. Wissenschaftliche Verlagsgesellschaft, Stuttgart

    Google Scholar 

  • OECD (2004a) Test Guideline 427: Skin Absorption: in vivo Method. Adopted on 13th April 2004

    Google Scholar 

  • OECD (2004b) Test Guideline 428: Skin Absorption: in vitro Method. Adopted on 13th April 2004

    Google Scholar 

  • Ogiso T, Niinaka N, Iwaki M (1996) Mechanism for enhancement effect of lipid disperse system on percutaneous absorption. J Pharm Sci 85:57–64

    CAS  PubMed  Google Scholar 

  • Otberg N, Richter H, Schaefer H, Blume-Peytavi U, Sterry W, Lademann J (2004) Variations of hair follicle size and distribution in different body sites. J Invest Dermatol 122:14–19

    CAS  PubMed  Google Scholar 

  • Ottaviani G, Martel S, Carrupt PA (2007) In silico and in vitro filters for the fast estimation of skin permeation and distribution of new chemical entities. J Med Chem 50:742–748

    CAS  PubMed  Google Scholar 

  • Paolino D, Cosco D, Muzzalupo R, Trapasso E, Picci N, Fresta M (2008) Innovative bola-surfactant niosomes as topical delivery systems of 5-fluorouracil for the treatment of skin cancer. Int J Pharm 353:233–242

    CAS  PubMed  Google Scholar 

  • Patravale VB, Mandawgade SD (2008) Novel cosmetic delivery systems: an application update. Int J Cosmet Sci 30:19–33

    CAS  PubMed  Google Scholar 

  • Pelchrzim R, Weigmann HJ, Schaefer H, Hagemeister T, Linscheid M, Shah VP, Sterry W, Lademann J (2004) Determination of the formation of the stratum corneum reservoir for two different corticosteroid formulations using tape stripping combined with UV/VIS spectroscopy. J Dtsch Dermatol Ges 2:914–919

    PubMed  Google Scholar 

  • Pershing LK, Silver BS, Krueger GG, Shah VP, Skelley JP (1992) Feasibility of measuring the bioavailability of topical betamethasone dipropionate in commercial formulations using drug content in skin and a skin blanching bioassay. Pharm Res 9:45–51

    CAS  PubMed  Google Scholar 

  • Pilgram GS, van der Meulen J, Gooris GS, Koerten HK, Bouwstra JA (2001) The influence of two azones and sebaceous lipids on the lateral organization of lipids isolated from human stratum corneum. Biochim Biophys Acta 1511:244–254

    CAS  PubMed  Google Scholar 

  • Rother M, Lavins BJ, Kneer W, Lehnhardt K, Seidel EJ, Mazgareanu S (2007) Efficacy and safety of epicutaneous ketoprofen in Transfersome (IDEA-033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial. Ann Rheum Dis 66:1178–1183

    CAS  PubMed  Google Scholar 

  • Rougier A, Lotte C, Maibach HI (1987) In vivo percutaneous penetration of some organic compounds related to anatomic site in humans: predictive assessment by the stripping method. J Pharm Sci 76:451–454

    CAS  PubMed  Google Scholar 

  • Roy SD, Flynn GL (1990) Transdermal delivery of narcotic analgesics: pH, anatomical, and subject influences on cutaneous permeability of fentanyl and sufentanil. Pharm Res 7:842–847

    CAS  PubMed  Google Scholar 

  • Ryman-Rasmussen JP, Riviere JE, Monteiro-Riviere NA (2006) Penetration of intact skin by quantum dots with diverse physicochemical properties. Toxicol Sci 91:159–165

    CAS  PubMed  Google Scholar 

  • Sanna V, Gavini E, Cossu M, Rassu G, Giunchedi P (2007) Solid lipid nanoparticles (SLN) as carriers for the topical delivery of econazole nitrate: in-vitro characterization, ex-vivo and in-vivo studies. J Pharm Pharmacol 59:1057–1064

    CAS  PubMed  Google Scholar 

  • Santos Maia C, Mehnert W, Schaller M, Korting HC, Gysler A, Haberland A, Schäfer-Korting M (2002) Drug targeting by solid lipid nanoparticles for dermal use. J Drug Targeting 10:489–495

    CAS  Google Scholar 

  • Santos P, Watkinson AC, Hadgraft J, Lane ME (2008) Application of microemulsions in dermal and transdermal drug delivery. Skin Pharmacol Physiol 21:246–259

    CAS  PubMed  Google Scholar 

  • SCCP (2007) The Scientific Committee on Cosmetic Products (SCCP) Opinion on safety of nanomaterials in cosmetic products. http://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_123.pdf

  • Schaefer H, Lademann J (2001) The role of follicular penetration. A differential view. Skin Pharmacol Appl Skin Physiol 14(Suppl 1):23–27

    PubMed  Google Scholar 

  • Schäfer-Korting M, Bock U, Diembeck W, Düsing HJ, Gamer A, Haltner-Ukomadu E, Hoffmann C, Kaca M, Kamp H, Kersen S, Kietzmann M, Korting HC, Krächter HU, Lehr CM, Liebsch M, Mehling A, Müller-Goymann C, Netzlaff F, Niedorf F, Rübbelke MK, Schäfer U, Schmidt E, Schreiber S, Spielmann H, Vuia A, Weimer M (2008a) The use of reconstructed human epidermis for skin absorption testing: results of the validation study. Altern Lab Anim 36:161–187

    PubMed  Google Scholar 

  • Schäfer-Korting M, Bock U, Gamer A, Haberland A, Haltner-Ukomadu E, Kaca M, Kamp H, Kietzmann M, Korting HC, Krächter HU, Lehr CM, Liebsch M, Mehling A, Netzlaff F, Niedorf F, Rübbelke MK, Schäfer U, Schmidt E, Schreiber S, Schröder KR, Spielmann H, Vuia A (2006) Reconstructed human epidermis for skin absorption testing: results of the German prevalidation study. Altern Lab Anim 34:283–294

    PubMed  Google Scholar 

  • Schäfer-Korting M, Korting HC, Kerscher MJ, Lenhard S (1993) Prednicarbate activity and benefit/risk ratio in relation to other topical glucocorticoids. Clin Pharmacol Ther 54:448–456

    PubMed  Google Scholar 

  • Schäfer-Korting M, Mahmoud A, Lombardi Borgia S, Brüggener B, Kleuser B, Schreiber S, Mehnert W (2008b) Reconstructed epidermis and full-thickness skin for absorption testing: Influences of vehicles on steroid permeation. Altern Lab Anim 36:441–452

    PubMed  Google Scholar 

  • Schäfer-Korting M, Mehnert W, Korting HC (2007) Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Deliv Rev 59:427–443

    PubMed  Google Scholar 

  • Schäfer-Korting M, Schmid MH, Korting HC (1996) Topical glucocorticoids with improved risk-benefit ratio. Rationale of a new concept. Drug Saf 14:375–385

    PubMed  Google Scholar 

  • Schaller M, Preidel H, Januschke E, Korting HC (1999) Light and electron microscopic findings in a model of human cutaneous candidosis based on reconstructed human epidermis following the topical application of different econazole formulations. J Drug Target 6:361–372

    CAS  PubMed  Google Scholar 

  • Schmook FP, Meingassner JG, Billich A (2001) Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption. Int J Pharm 215:51–56

    CAS  PubMed  Google Scholar 

  • Schöler N, Hahn H, Müller RH, Liesenfeld O (2002) Effect of lipid matrix and size of solid lipid nanoparticles (SLN) on the viability and cytokine production of macrophages. Int J Pharm 231:167–176

    PubMed  Google Scholar 

  • Schöler N, Olbrich C, Tabatt K, Müller RH, Hahn H, Liesenfeld O (2001) Surfactant, but not the size of solid lipid nanoparticles (SLN) influences viability and cytokine production of macrophages. Int J Pharm 221:57–67

    PubMed  Google Scholar 

  • Schreiber S, Mahmoud A, Vuia A, Rübbelke MK, Schmidt E, Schaller M, Kandarova H, Haberland A, Schäfer UF, Bock U, Korting HC, Liebsch M, Schäfer-Korting M (2005) Reconstructed epidermis versus human and animal skin in skin absorption studies. Toxicol In Vitro 19:813–822

    CAS  PubMed  Google Scholar 

  • Shah VP (2001) Progress in methodologies for evaluating bioequivalence of topical formulations. Am J Clin Dermatol 2:275–280

    CAS  PubMed  Google Scholar 

  • Shah VP, Flynn GL, Yacobi A, Maibach HI, Bon C, Fleischer NM, Franz TJ, Kaplan SA, Kawamoto J, Lesko LJ, Marty JP, Pershing LK, Schaefer H, Sequeira JA, Shrivastava SP, Wilkin J, Williams RL (1998) Bioequivalence of topical dermatological dosage forms – methods of evaluation of bioequivalence. Pharm Res 15:167–171

    CAS  PubMed  Google Scholar 

  • Sivaramakrishnan R, Nakamura C, Mehnert W, Korting HC, Kramer KD, Schäfer-Korting M (2004) Glucocorticoid entrapment into lipid carriers – characterisation by parelectric spectroscopy and influence on dermal uptake. J Control Release 97:493–502

    CAS  Google Scholar 

  • Song C, Liu S (2005) A new healthy sunscreen system for human: solid lipid nanoparticles as carrier for 3, 4, 5-trimethoxybenzoylchitin and the improvement by adding vitamin E. Int J Biol Macromol 36:116–119

    CAS  PubMed  Google Scholar 

  • Stecova J, Mehnert W, Blaschke T, Kleuser B, Sivaramakrishnan R, Zouboulis CC, Seltmann H, Korting HC, Kramer KD, Schäfer-Korting M (2007) Cyproterone acetate loading to lipid nanoparticles for topical acne treatment: particle characterisation and skin uptake. Pharm Res 24:991–1000

    CAS  PubMed  Google Scholar 

  • Stern ST, McNeil SE (2008) Nanotechnology safety concerns revisited. Toxicol Sci 101:4–21

    CAS  PubMed  Google Scholar 

  • Takahashi A, Suzuki S, Kawasaki N, Kubo W, Miyazaki S, Loebenberg R, Bachynsky J, Attwood D (2002) Percutaneous absorption of non-steroidal anti-inflammatory drugs from in situ gelling xyloglucan formulations in rats. Int J Pharm 246:179–186

    CAS  PubMed  Google Scholar 

  • Teichmann A, Jacobi U, Ossadnik M, Richter H, Koch S, Sterry W, Lademann J (2005) Differential stripping: determination of the amount of topically applied substances penetrated into the hair follicles. J Invest Dermatol 125:264–269

    CAS  PubMed  Google Scholar 

  • Teichmann A, Ossadnik M, Richter H, Sterry W, Lademann J (2006) Semiquantitative determination of the penetration of a fluorescent hydrogel formulation into the hair follicle with and without follicular closure by microparticles by means of differential stripping. Skin Pharmacol Physiol 19:101–105

    CAS  PubMed  Google Scholar 

  • Thong HY, Zhai H, Maibach HI (2007) Percutaneous penetration enhancers: an overview. Skin Pharmacol Physiol 20:272–282

    PubMed  Google Scholar 

  • Toll R, Jacobi U, Richter H, Lademann J, Schaefer H, Blume-Peytavi U (2004) Penetration profile of microspheres in follicular targeting of terminal hair follicles. J Invest Dermatol 123:168–176

    CAS  PubMed  Google Scholar 

  • Touitou E, Dayan N, Bergelson L, Godin B, Eliaz M (2000) Ethosomes – novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J Control Release 65:403–418

    CAS  Google Scholar 

  • Trotta M, Peira E, Carlotti ME, Gallarate M (2004) Deformable liposomes for dermal administration of methotrexate. Int J Pharm 270:119–125

    CAS  PubMed  Google Scholar 

  • Tsai JC, Lin CY, Sheu HM, Lo YL, Huang YH (2003) Noninvasive characterization of regional variation in drug transport into human stratum corneum in vivo. Pharm Res 20:632–638

    CAS  PubMed  Google Scholar 

  • Ulrich C, Degen A, Patel MJ, Stockfleth E (2008) Sunscreens in organ transplant patients. Nephrol Dial Transplant 23:2712

    Google Scholar 

  • Vickers CF, Fritsch WC (1963) A hazard of plastic film therapy. Arch Dermatol 87:633–636

    CAS  PubMed  Google Scholar 

  • Wagner H, Kostka KH, Adelhardt W, Schaefer UF (2004) Effects of various vehicles on the penetration of flufenamic acid into human skin. Eur J Pharm Biopharm 58:121–129

    CAS  PubMed  Google Scholar 

  • Wagner H, Kostka KH, Lehr CM, Schaefer UF (2002a) Correlation between stratum corneum/water-partition coefficient and amounts of flufenamic acid penetrated into the stratum corneum. J Pharm Sci 91:1915–1921

    CAS  PubMed  Google Scholar 

  • Wagner H, Kostka KH, Lehr CM, Schaefer UF (2002b) Human skin penetration of flufenamic acid: in vivo/in vitro correlation (deeper skin layers) for skin samples from the same subject. J Invest Dermatol 118:540–544

    CAS  PubMed  Google Scholar 

  • Weigmann H, Lademann J, Meffert H, Schaefer H, Sterry W (1999) Determination of the horny layer profile by tape stripping in combination with optical spectroscopy in the visible range as a prerequisite to quantify percutaneous absorption. Skin Pharmacol Appl Skin Physiol 12:34–45

    CAS  PubMed  Google Scholar 

  • Weigmann HJ, Jacobi U, Antoniou C, Tsikrikas GN, Wendel V, Rapp C, Gers-Barlag H, Sterry W, Lademann J (2005) Determination of penetration profiles of topically applied substances by means of tape stripping and optical spectroscopy: UV filter substance in sunscreens. J Biomed Opt 10:14009

    PubMed  Google Scholar 

  • Weinstein GD, McCullough JL, Olsen E (1989) Topical methotrexate therapy for psoriasis. Arch Dermatol 125:227–230

    CAS  PubMed  Google Scholar 

  • Weyenberg W, Filev P, Van den Plas D, Vandervoort J, De Smet K, Sollie P, Ludwig A (2007) Cytotoxicity of submicron emulsions and solid lipid nanoparticles for dermal application. Int J Pharm 337:291–298

    CAS  PubMed  Google Scholar 

  • Wilsmann-Theis D, Hagemann T, Jordan J, Bieber T, Novak N (2008) Facing psoriasis and atopic dermatitis: are there more similarities or more differences? Eur J Dermatol 18:172–180

    PubMed  Google Scholar 

  • Zhang LW, Yu WW, Colvin VL, Monteiro-Riviere NA (2008) Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes. Toxicol Appl Pharmacol 228:200–211

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hans Christian Korting or Monika Schäfer-Korting .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Korting, H.C., Schäfer-Korting, M. (2010). Carriers in the Topical Treatment of Skin Disease. In: Schäfer-Korting, M. (eds) Drug Delivery. Handbook of Experimental Pharmacology, vol 197. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00477-3_15

Download citation