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Perspectives on Using Nanoscale Delivery Systems in Dermatological Treatment

Current Dermatology Reports volume 4, pages 1–7 (2015)Cite this article

Abstract

Nanotechnology may potentially revolutionize the foundation of disease treatment and prevention at cellular and molecular levels. Unlike conventional therapies, which often suffer from lack of specificity and dose-related side effects, nanomedicine will bring nano-sized particulate systems to enhance bioavailability of therapeutics as well as their delivery in a site-specific manner, thus, resulting in increased therapeutic index while limiting toxicity. Nanoparticles, constructed from a wide range of biomaterials, can be exploited to efficiently deliver biotherapeutics into the skin in order to improve dermatological treatments. This review provides a perspective on nanoscale delivery systems designed for topical delivery of small drugs, peptides/proteins, and nucleic acids.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Blecher PK, Friedman A. Nanotechnology and the diagnosis of dermatological infectious disease. J Drugs Dermatol: JDD. 2012;11(7):846–51.

    Google Scholar 

  2. DeLouise LA. Applications of nanotechnology in dermatology. J Investig Dermatol. 2012;132:964–75.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Rizzo LY et al. Recent progress in nanomedicine: Therapeutic, diagnostic and theranostic applications. Curr Opin Biotechnol. 2013;24(6):1159–66.

    Article  CAS  PubMed  Google Scholar 

  4. Alex SM, Sharma CP. Nanomedicine for gene therapy. Drug Deliv Transl Res. 2013;3(5):437–45.

    Article  CAS  Google Scholar 

  5. Yah CS. The toxicity of gold nanoparticles in relation to their physiochemical properties. Biomed Res. 2013;24:400–13.

    CAS  Google Scholar 

  6. Elias PM. Epidermal lipids, barrier function, and desquamation. J Investig Dermatol. 1983;80:44s–9.

    Article  CAS  Google Scholar 

  7. Abraham W, Downing DT. Lamellar structures formed by stratum corneum lipids in vitro: a deuterium nuclear magnetic resonance (NMR) study. Pharm Res. 1992;9(11):1415–21.

    Article  CAS  PubMed  Google Scholar 

  8. Tojo K. Random brick model for drug transport across stratum corneum. J Pharm Sci. 1987;76(12):889–91.

    Article  CAS  PubMed  Google Scholar 

  9. Bos JD, Meinardi MM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9(3):165–9.

    Article  CAS  PubMed  Google Scholar 

  10. Johnson ME, Blankschtein D, Langer R. Evaluation of solute permeation through the stratum corneum: Lateral bilayer diffusion as the primary transport mechanism. J Pharm Sci. 1997;86(10):1162–72.

    Article  CAS  PubMed  Google Scholar 

  11. Bouwstra JA, Ponec M. The skin barrier in healthy and diseased state. Biochim Biophys Acta (BBA)-Biomembr. 2006;1758(12):2080–95.

    Article  CAS  Google Scholar 

  12. Cevc G. Lipid vesicles and other colloids as drug carriers on the skin. Adv Drug Deliv Rev. 2004;56(5):675–711.

    Article  CAS  PubMed  Google Scholar 

  13. Tang H et al. Theoretical description of transdermal transport of hydrophilic permeants: Application to low-frequency sonophoresis. J Pharm Sci. 2001;90(5):545–68.

    Article  CAS  PubMed  Google Scholar 

  14. Potts RO, Francoeur ML. The influence of stratum corneum morphology on water permeability. J Investig Dermatol. 1991;96(4):495–9.

    Article  CAS  PubMed  Google Scholar 

  15. Winkler A, Muller-Goymann CC. The influence of topical formulations on the permeation of 5-aminolevulinic acid and its n-butyl ester through excised human stratum corneum. Eur J Pharm Biopharm. 2005;60(3):427–37.

    Article  CAS  PubMed  Google Scholar 

  16. Bouwstra JA et al. The role of ceramides 1 and 2 in the stratum corneum lipid organisation. Biochim Biophys Acta (BBA)-Lipids Lipid Metab. 1996;1300(3):177–86.

    Article  Google Scholar 

  17. Lopez O et al. Different stratum corneum lipid liposomes as models to evaluate the effect of the sodium dodecyl sulfate. Biochim Biophys Acta (BBA)-Biomembr. 2000;1508(1):196–209.

    Article  CAS  Google Scholar 

  18. Chesnoy S et al. Effect of iontophoresis in combination with ionic enhancers on the lipid structure of the stratum corneum: an X-ray diffraction study. Pharm Res. 1996;13(10):1581–4.

    Article  CAS  PubMed  Google Scholar 

  19. Bouwstra JA et al. Structural investigations of human stratum corneum by small-angle X-ray scattering. J Investig Dermatol. 1991;97(6):1005–12.

    Article  CAS  PubMed  Google Scholar 

  20. Foldvari M, Gharagozloo M, Li C. Nanoparticles for dermal and transdermal delivery: Permeation pathways and applications. In: Torchilin V, editor. Handbook of nanobiomedical research. Singapore: World Scientific; 2014. p. 231–60. This chapter provides a comprehensive review of all nanoparticle types designed and evaluated for dermal and transdermal drug delivery including coverage of nanoparticle properties, mechanism of interaction with the skin and interpretation of relative usefullness in clinical applications.

    Chapter  Google Scholar 

  21. Santos Maia C et al. Drug targeting by solid lipid nanoparticles for dermal use. J Drug Target. 2002;10(6):489–95.

    Article  CAS  PubMed  Google Scholar 

  22. Lee AL et al. Block copolymer mixtures as antimicrobial hydrogels for biofilm eradication. Biomaterials. 2013;34(38):10278–86.

    Article  CAS  PubMed  Google Scholar 

  23. Erdogan M, Wright J, McAlister V. Liposomal tacrolimus lotion as a novel topical agent for treatment of immune-mediated skin disorders: Experimental studies in a murine model. Br J Dermatol. 2002;146(6):964–7.

    Article  CAS  PubMed  Google Scholar 

  24. Li G et al. Tacrolimus-loaded ethosomes: Physicochemical characterization and in vivo evaluation. Eur J Pharm Biopharm. 2012;82(1):49–57.

    Article  CAS  PubMed  Google Scholar 

  25. Pople PV, Singh KK. Development and evaluation of colloidal modified nanolipid carrier: application to topical delivery of tacrolimus, Part II–in vivo assessment, drug targeting, efficacy, and safety in treatment for atopic dermatitis. Eur J Pharm Biopharm. 2013;84(1):72–83.

    Article  CAS  PubMed  Google Scholar 

  26. Cevc G, Blume G. Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim Biophys Acta (BBA)-Biomembr. 1992;1104(1):226–32.

    Article  CAS  Google Scholar 

  27. Elsayed M et al. Lipid vesicles for skin delivery of drugs: reviewing three decades of research. Int J Pharm. 2007;332(1):1–16.

    Article  CAS  PubMed  Google Scholar 

  28. Muller R, Radtke M, Wissing S. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002;54:S131–55.

    Article  CAS  PubMed  Google Scholar 

  29. Muller RH, Shegokar R, Keck CM. 20 years of lipid nanoparticles (SLN and NLC): present state of development and industrial applications. Curr Drug Discov Technol. 2011;8(3):207–27.

    Article  PubMed  Google Scholar 

  30. Vaghasiya H, Kumar A, Sawant K. Development of solid lipid nanoparticles based controlled release system for topical delivery of terbinafine hydrochloride. Eur J Pharm Sci. 2013;49(2):311–22.

    Article  CAS  PubMed  Google Scholar 

  31. Gasco MR. Method for producing solid lipid microspheres having a narrow size distribution. Google Patents; 1993.

  32. Puglia C, Bonina F. Lipid nanoparticles as novel delivery systems for cosmetics and dermal pharmaceuticals. Expert Opin Drug Deliv. 2012;9(4):429–41.

    Article  CAS  PubMed  Google Scholar 

  33. Iqbal MA et al. Nanostructured lipid carriers system: recent advances in drug delivery. J Drug Target. 2012;20(10):813–30.

    Article  CAS  PubMed  Google Scholar 

  34. Nam SH, Ji XY, Park J-S. Investigation of tacrolimus loaded nanostructured lipid carriers for topical drug delivery. Bull Korean Chem Soc. 2011;32:956–60.

    Article  CAS  Google Scholar 

  35. Pople PV, Singh KK. Targeting tacrolimus to deeper layers of skin with improved safety for treatment of atopic dermatitis. Int J Pharm. 2010;398(1):165–78.

    Article  CAS  PubMed  Google Scholar 

  36. Shah PP et al. Enhanced skin permeation using polyarginine modified nanostructured lipid carriers. J Control Release. 2012;161(3):735–45.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Desai PR et al. Investigation of follicular and non-follicular pathways for polyarginine and oleic acid-modified nanoparticles. Pharm Res. 2013;30(4):1037–49.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Papakostas D et al. Nanoparticles in dermatology. Arch Dermatol Res. 2011;303(8):533–50.

    Article  CAS  PubMed  Google Scholar 

  39. Alvarez-Roman R et al. Skin penetration and distribution of polymeric nanoparticles. J Control Release. 2004;99(1):53–62.

    Article  CAS  PubMed  Google Scholar 

  40. Abdel-Mottaleb M et al. Surface-charge-dependent nanoparticles accumulation in inflamed skin. J Pharm Sci. 2012;101(11):4231–9.

    Article  CAS  PubMed  Google Scholar 

  41. Qiao Y, Bai X-F, Du Y-G. Chitosan oligosaccharides protect mice from LPS challenge by attenuation of inflammation and oxidative stress. Int Immunopharmacol. 2011;11(1):121–7.

    Article  CAS  PubMed  Google Scholar 

  42. Rossi S et al. Wound dressings based on chitosans and hyaluronic acid for the release of chlorhexidine diacetate in skin ulcer therapy. Pharm Dev Technol. 2007;12(4):415–22.

    Article  CAS  PubMed  Google Scholar 

  43. Pinto RJ et al. Antibacterial activity of optically transparent nanocomposite films based on chitosan or its derivatives and silver nanoparticles. Carbohydr Res. 2012;348:77–83.

    Article  CAS  PubMed  Google Scholar 

  44. Tan Q et al. Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery. Int J Nanomedicine. 2011;6:1621.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Morishita M, Park K (eds.) Biodrug delivery systems: fundamentals, applications, and clinical development. Informa 2009.

  46. Antosova Z et al. Therapeutic application of peptides and proteins: Parenteral forever? Trends Biotechnol. 2009;27(11):628–35.

    Article  CAS  PubMed  Google Scholar 

  47. McCrudden MT et al. Strategies for enhanced peptide and protein delivery. Ther Deliv. 2013;4(5):593–614. This review paper critically discusses protein and peptide delivery by different routes of administration and provides an excellent perspective on the challenges involved.

    Article  CAS  PubMed  Google Scholar 

  48. Bodde HE, Verhoef JC, Ponec M. Transdermal peptide delivery. Biochem Soc Trans. 1989;17(5):943–5.

    CAS  PubMed  Google Scholar 

  49. Dawson BV et al. In vitro transdermal delivery of a melanotropic peptide through human skin. J Investig Dermatol. 1990;94(4):432–5.

    Article  CAS  PubMed  Google Scholar 

  50. Foldvari M et al. Palmitoyl derivatives of interferon alpha: Potential for cutaneous delivery. J Pharm Sci. 1998;87(10):1203–8.

    Article  CAS  PubMed  Google Scholar 

  51. Foldvari M et al. Dermal and transdermal delivery of protein pharmaceuticals: Lipid-based delivery systems for interferon alpha. Biotechnol Appl Biochem. 1999;30(Pt 2):129–37.

    CAS  PubMed  Google Scholar 

  52. Martins S et al. Lipid-based colloidal carriers for peptide and protein delivery—Liposomes versus lipid nanoparticles. Int J Nanomedicine. 2007;2(4):595–607.

    PubMed Central  CAS  PubMed  Google Scholar 

  53. Pierre MB, Dos Santos Miranda Costa I. Liposomal systems as drug delivery vehicles for dermal and transdermal applications. Arch Dermatol Res. 2011;303(9):607–21.

    Article  CAS  PubMed  Google Scholar 

  54. Foldvari M. Biphasic vesicles: a novel topical drug delivery system. J Biomed Nanotechnol. 2010;6(5):543–57.

    Article  CAS  PubMed  Google Scholar 

  55. Foldvari M et al. Topical delivery of interferon alpha by biphasic vesicles: Evidence for a novel nanopathway across the stratum corneum. Mol Pharm. 2010;7(3):751–62.

    Article  CAS  PubMed  Google Scholar 

  56. Foldvari M et al. Biphasic vesicles for topical delivery of interferon alpha in human volunteers and treatment of patients with human papillomavirus infections. Curr Drug Deliv. 2011;8(3):307–19. This paper describes biphasic vesicles, a novel delivery system and the first topical cream suitable for delivering a large protein into the skin and mucosa in humans.

    Article  CAS  PubMed  Google Scholar 

  57. King M et al. In vivo sustained dermal delivery and pharmacokinetics of interferon alpha in biphasic vesicles after topical application. Eur J Pharm Biopharm. 2013;84(3):532–9.

    Article  CAS  PubMed  Google Scholar 

  58. Foldvari M, Moreland A, Mezei M. Topical liposome-encapsulated interferon-alpha for the treatment of genital papillomavirus infections. J Investig Dermatol. 1989;93(4):550.

    Google Scholar 

  59. Foldvari M et al. Dermal and transdermal delivery of protein pharmaceuticals: Lipid-based delivery systems for interferon alpha. Biotechnol Appl Biochem. 1999;30:129–37.

    CAS  PubMed  Google Scholar 

  60. Foldvari M, Kumar P. Recent progress in the application of nanotechnology for prevention and treatment of human papillomavirus infection. Ther Deliv. 2012;3(8):1005–17.

    Article  CAS  PubMed  Google Scholar 

  61. Kumar P et al. Stabilization of interferon alpha-2b in a topical cream. Pharm Technol. 2009;33(7):80–6.

    CAS  Google Scholar 

  62. Kurzeja R, Bohmer G, Schneider A. Clinical outcome of topical interferon alpha-2b cream in Phase II trial for LSIL/CIN patients. J Cancer Ther. 2011;2:203–8.

    Article  CAS  Google Scholar 

  63. Getie M, Wohlrab J, Neubert RH. Dermal delivery of desmopressin acetate using colloidal carrier systems. J Pharm Pharmacol. 2005;57(4):423–7.

    Article  CAS  PubMed  Google Scholar 

  64. Goebel AS et al. Dermal peptide delivery using enhancer molecules and colloidal carrier systems–part I: carnosine. Skin Pharmacol Physiol. 2012;25(6):281–7.

    Article  CAS  PubMed  Google Scholar 

  65. Russell-Jones G, Himes R. Water-in-oil microemulsions for effective transdermal delivery of proteins. Expert Opin Drug Deliv. 2011;8(4):537–46.

    Article  CAS  PubMed  Google Scholar 

  66. Gainza G et al. A novel strategy for the treatment of chronic wounds based on the topical administration of rhEGF-loaded lipid nanoparticles: In vitro bioactivity and in vivo effectiveness in healing-impaired db/db mice. J Control Release. 2014;185:51–61.

    Article  CAS  PubMed  Google Scholar 

  67. Dou C et al. Strengthening the skin with topical delivery of keratinocyte growth factor-1 using a novel DNA plasmid. Mol Ther. 2014;22(4):752–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Li J et al. Gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal delivery of interleukin-4 using ultradeformable cationic liposome. J Gene Med. 2010;12(6):481–90.

    Article  CAS  PubMed  Google Scholar 

  69. Menger FM, Littau C. Gemini-surfactants: Synthesis and properties. J Am Chem Soc. 1991;113(4):1451–2.

    Article  CAS  Google Scholar 

  70. Foldvari M et al. Structural characterization of novel gemini non-viral DNA delivery systems for cutaneous gene therapy. J Exp Nanosci. 2006;1(2):165–76.

    Article  CAS  Google Scholar 

  71. Wettig SD, Verrall RE, Foldvari M. Gemini surfactants: a new family of building blocks for non-viral gene delivery systems. Curr Gene Ther. 2008;8(1):9–23.

    Article  CAS  PubMed  Google Scholar 

  72. Badea I et al. In vivo cutaneous interferon-γ gene delivery using novel dicationic (gemini) surfactant-plasmid complexes. J Gene Med. 2005;7(9):1200–14.

    Article  CAS  PubMed  Google Scholar 

  73. Badea I et al. Effect of topical interferon-gamma gene therapy using gemini nanoparticles on pathophysiological markers of cutaneous scleroderma in Tsk/+ mice. Gene Ther. 2012;19(10):978–87. This study was first to show that topical gene therapy, using a novel non-viral gemini-nanoparticle technology, is a feasible approach for the modulation of excessive collagen synthesis in scleroderma-affected skin.

    Article  CAS  PubMed  Google Scholar 

  74. Badea I et al. Pathogenesis and therapeutic approaches for improved topical treatment in localized scleroderma and systemic sclerosis. Rheumatology. 2009;48(3):213–21.

    Article  CAS  PubMed  Google Scholar 

  75. Badea I et al. Topical non-invasive gene delivery using gemini nanoparticles in interferon-gamma-deficient mice. Eur J Pharm Biopharm. 2007;65(3):414–22.

    Article  CAS  PubMed  Google Scholar 

  76. Takanashi M et al. Therapeutic silencing of an endogenous gene by siRNA cream in an arthritis model mouse. Gene Ther. 2009;16(8):982–9. In this paper a topical ‘gene cream’ is evaluated and was shown to be effective in delivering and achieving a functional response of siRNA.

    Article  CAS  PubMed  Google Scholar 

  77. Zheng D et al. Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation. Proc Natl Acad Sci. 2012;109(30):11975–80. This paper showed the high efficiency of covalently immobilized siRNA on gold nanoparticles to penetrate keratinocytes in vitro, mouse skin, and human epidermis within few hours after application.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

The research in this paper was supported by grants from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, and the Ontario Research Fund. The generous support of the Canada Research Chairs Program is also gratefully acknowledged (M. Foldvari).

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Conflict of Interest

M Foldvari has received consulting fees from Helix BioPharma Corporation and has a patent lipid vesicle compositions pending, and a patent Multicompartmental lipid vesicle compositions pending.

A Rafiee declares no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. School of Pharmacy and Waterloo Institute of Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, ON, N2L 3G1, Canada

    Marianna Foldvari & Amirreza Rafiee

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  1. Marianna Foldvari
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  2. Amirreza Rafiee
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Correspondence to Marianna Foldvari.

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This article is part of the Topical Collection on Immunology

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Foldvari, M., Rafiee, A. Perspectives on Using Nanoscale Delivery Systems in Dermatological Treatment. Curr Derm Rep 4, 1–7 (2015). https://doi.org/10.1007/s13671-014-0092-z

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  • DOI: https://doi.org/10.1007/s13671-014-0092-z

Keywords

  • Nanomedicine
  • Topical delivery
  • Nanoparticles
  • Biotherapeutics
  • Protein delivery
  • Nucleic acid delivery