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Nanocosmetics pp 161–177Cite as

Nanocrystals for Dermal Application

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Abstract

Dermal application of actives aims at delivering the active to the desired place of action, typically to the deeper layers of the skin. Passive diffusion is the main driving force of absorption into the skin, and a main prerequisite for effective passive diffusion is a sufficient amount of dissolved active within the formulation, because only dissolved molecules can be taken up. Many cosmetic and cosmeceutical actives possess poor solubility and can therefore not be delivered to the skin by classical formulation approaches. One of the modern and most powerful strategies to overcome poor solubility is the use of nanocrystals, which are addressed in this chapter.

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References

  1. Scheuplein RJ. Analysis of permeability data for the case of parallel diffusion pathways. Biophys J. 1966;6:1–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Scheuplein RJ, Blank IH. Permeability of the skin. Physiol Rev. 1971;51:702–47.

    Article  CAS  PubMed  Google Scholar 

  3. Godin B, Touitou E. Transdermal skin delivery: predictions for humans from in vivo, ex vivo and animal models. Adv Drug Deliv. 2007;59:1152–61.

    Article  CAS  Google Scholar 

  4. Norlén L. Skin barrier formation, The membrane folding model. J Invest Dermatol. 2001;117(4):823–9.

    Article  PubMed  Google Scholar 

  5. Kreilgaard M. Influence of microemulsions on cutaneous drug delivery. Adv Drug Deliv. 2002;54:77–98.

    Article  Google Scholar 

  6. Pawar KR, Babu RJ. Lipid materials for topical and transdermal delivery of nanoemulsions. Crit Rev Ther Drug Carrier Syst. 2014;31:429–58.

    Article  PubMed  Google Scholar 

  7. Junyaprasert VB, Teeranachaideekul V, Souto EB, et al. Q10-loaded NLC versus nanoemulsions: stability, rheology and in vitro skin permeation. Int J Pharm. 2009;377:207–14.

    Article  CAS  PubMed  Google Scholar 

  8. Roberts MS, Mohammed Y, Pastore MN, et al. Topical and cutaneous delivery using nanosystems. J Control Release. 2017;247:86–105.

    Article  CAS  PubMed  Google Scholar 

  9. Müller RH, Gohla S, Keck CM. State of the art of nanocrystals—special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm. 2011;78(1):1–9.

    Article  PubMed  Google Scholar 

  10. Keck CM, Müller RH. Nanodiamanten - Erhöhte Bioaktivitat. Labor & More. 2008;01(08):64–5.

    Google Scholar 

  11. Keck CM, Müller RH. Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation. Eur J Pharm Biopharm. 2006;62(1):3–16.

    Article  CAS  PubMed  Google Scholar 

  12. Keck CM, Al Shaal L, Müller RH. SmartCrystals®—review of the second generation of drug nanocrystals. Handbook of materials for nanomedicine. In: Torchilin VP, Amiji MM, Editors. Pan stanford series on biomedical nanotechnology, London: Pan Stanford Publishing; 2010. p. 555–80.

    Google Scholar 

  13. Müller RH, Keck CM. Challenges and solutions for the delivery of biotech drugs—a review of drug nanocrystal technology and lipid nanoparticles. J Biotechnol. 2004;113(1–3):151–70.

    Article  PubMed  Google Scholar 

  14. Mauludin R, Müller RH, Keck CM. Kinetic solubility and dissolution velocity of rutin nanocrystals. Eur J Pharm Sci. 2009;36(4–5):502–10.

    Article  CAS  PubMed  Google Scholar 

  15. Müller RH, Keck CM. Twenty years of drug nanocrystals. Where are we, and where do we go? Eur J Pharm Biopharm. 2012;80(1):1–3.

    Article  PubMed  Google Scholar 

  16. Mauludin R, Müller RH, Keck CM. Development of an oral rutin nanocrystal formulation. Int J Pharm. 2009;370(1–2):202–9.

    Article  CAS  PubMed  Google Scholar 

  17. Rabinow BE. Nanosuspensions in drug delivery. Nat Rev Drug Discov. 2004;3(9):785–96.

    Article  CAS  PubMed  Google Scholar 

  18. Merisko-Liversidge E, Liversidge GG, Cooper ER. Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci. 2003;18(2):113–20.

    Article  CAS  PubMed  Google Scholar 

  19. Stegemann S, Leveiller F, Franchi D, et al. When poor solubility becomes an issue. From early stage to proof of concept. Eur J Pharm Sci. 2007;31(5):249–61.

    Article  CAS  PubMed  Google Scholar 

  20. Müller RH, Keck CM. Second generation of drug nanocrystals for delivery of poorly soluble drugs: SmartCrystal®-technology. Eur J Pharm Sci. 2008;34(1):20–1.

    Article  Google Scholar 

  21. Liversidge GG, Cundy KC. Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs. Int J Pharm. 1995;125(1):91–7.

    Article  CAS  Google Scholar 

  22. Merisko-Liversidge E, Liversidge GG. Nanosizing for oral and parenteral drug delivery. A perspective on formulating poorly-water soluble compounds using wet media milling technology. Adv Drug Deliv Rev. 2011;63(6):427–40.

    Article  CAS  PubMed  Google Scholar 

  23. Zhai X, Lademann J, Keck CM, et al. Nanocrystals of medium soluble actives—novel concept for improved dermal delivery and production strategy. Int J Pharm. 2014;470(1–2):141–50.

    Article  CAS  PubMed  Google Scholar 

  24. Liversidge GG, Cundy KC, Bishop JF, et al. Surface modified drug nanoparticles. US Patent 5,145,684; (1992).

    Google Scholar 

  25. Michael JM, Thomas ER, Atkins J. Microencapsulated 3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles. US Patent 5,965,168; 1992.

    Google Scholar 

  26. Müller RH, Akkar A. Drug nanocrystals of poorly soluble drugs. Encyclopedia of Nanoscience and Nanotechnology (Nalwa HS, Editor), American Scientific Publishers; (2004). p. 627–38.

    Google Scholar 

  27. Mishra PR, Al Shaal L, Müller RH, et al. Production and characterization of Hesperetin nanosuspensions for dermal delivery. Int J Pharm. 2009;371(1–2):182–9.

    Article  CAS  PubMed  Google Scholar 

  28. Gassmann P, List M, Schweitzer A, Sucker H. Hydrosols—Alternatives for the parenteral application of poorly water soluble drugs. Eur J Pharm Biopharm. 1994;40:64–72.

    CAS  Google Scholar 

  29. List M, Sucker H. Pharmaceutical colloidal hydrosols for injection. GB Patent 2,200,048; 1988.

    Google Scholar 

  30. Auweter H, Bohn H, Heger R, et al. Precipitated water-insoluble colorants in colloid disperse form. US Patent 6,494,924; 2002.

    Google Scholar 

  31. Merisko-Liversidge E, Sarpotdar P, Bruno J, et al. Formulation and antitumor activity evaluation of nanocrystalline suspensions of poorly soluble anticancer drugs. Pharm Res. 1996;13(2):272–8.

    Article  CAS  PubMed  Google Scholar 

  32. Petersen RD. Nanocrystals for use in topical formulations and method of production thereof; 2006. PCT/EP2007/009943.

    Google Scholar 

  33. Scholz P, Arntjen A, Müller RH, et al. ARTcrystal® process for industrial nanocrystal production—optimization of the ART MICCRA® pre-milling step. Int J Pharm. 2014;465(1–2):388–95.

    Article  CAS  PubMed  Google Scholar 

  34. Scholz P, Keck CM. Flavonoid nanocrystals produced by ARTcrystal®-technology. Int J Pharm. 2015;482(1–2):27–37.

    Article  CAS  PubMed  Google Scholar 

  35. Salazar J, Müller RH, Möschwitzer JP. Performance comparison of two novel combinative particle-size-reduction technologies. J Pharm Sci. 2013;102(5):1636–49.

    Article  CAS  PubMed  Google Scholar 

  36. Scholz P, Keck CM. Ibuprofen nanocrystals produced by ArtCrystal-technology. Pharm Ind. 2016;9(16):1340–54.

    Google Scholar 

  37. Salazar J, Ghanem A, Müller RH, et al. Nanocrystals: comparison of the size reduction effectiveness of a novel combinative method with conventional top-down approaches. Eur J Pharm Biopharm. 2012;81(1):82–90.

    Article  CAS  PubMed  Google Scholar 

  38. Keck CM. Cyclosporine nanosuspensions: optimised size characterisation & oral formulations, PhD-thesis, Freie Universität Berlin; 2006.

    Google Scholar 

  39. Kobierski S, Keck CM. Production of Hesperidin dermal nanocrystals by novel smartCrystal® combination technology, 10th European Workshop on Particulate Systems, Berlin/Germany, 30th–31th May; 2008.

    Google Scholar 

  40. Romero GB, Chen R, Keck CM, et al. Industrial concentrates of dermal hesperidin smartCrystals®–production, characterization & long-term stability. Int J Pharm. 2015;482(1–2):54–60.

    Article  CAS  PubMed  Google Scholar 

  41. Al Shaal L, Müller RH, Keck CM. Preserving hesperetin nanosuspensions for dermal application. Die Pharmazie. 2010;65(2):86–92.

    CAS  PubMed  Google Scholar 

  42. Kobierski S, Ofori-Kwakye K, Müller RH, et al. Resveratrol nanosuspensions. Interaction of preservatives with nanocrystal production. Die Pharmazie. 2011;66(12):942–7.

    CAS  PubMed  Google Scholar 

  43. Obeidat WM, Schwabe K, Müller RH, et al. Preservation of nanostructured lipid carriers (NLC). Eur J Pharm Biopharm. 2010;76(1):56–67.

    Article  CAS  PubMed  Google Scholar 

  44. Rachmawati H, Rahma A, Al Shaal L, et al. Destabilization mechanism of ionic surfactant on curcumin nanocrystal against electrolytes. Sci Pharm. 2016;84(4):685–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kessler M, Ubeaud GJL. Anti- and pro-oxidant activity of rutin and quercetin derivatives. J Pharm Pharmacol. 2003;55:131–42.

    Article  CAS  PubMed  Google Scholar 

  46. Stahr P, Keck CM. Tailor-made nanocrystals for optimised dermal drug delivery, 5th Galenus Workshop, Berlin/Germany, 16th–18th November; 2016.

    Google Scholar 

  47. Braun A, Stahr P, Schäfer K-H, Keck CM. SmartCrystals® for neuroprotection, Menopause, Andropause, Anti-Aging-Kongress, Vienna/Austria, 8th–10th December; 2016.

    Google Scholar 

  48. Al Shaal L, Mishra PR, Müller RH, et al. Nanosuspensions of hesperetin. Preparation and characterization. Die Pharmazie. 2014;69(3):173–82.

    CAS  PubMed  Google Scholar 

  49. Hatahet T, Morille M, Hommoss A, et al. Dermal quercetin smartCrystals®. Formulation development, antioxidant activity and cellular safety. Eur J Pharm Biopharm. 2016;102:51–63.

    Article  CAS  PubMed  Google Scholar 

  50. Vidlářová L, Romero GB, Hanuš J, et al. Nanocrystals for dermal penetration enhancement—effect of concentration and underlying mechanisms using curcumin as model. Eur J Pharm Biopharm. 2016;104:216–25.

    Article  PubMed  Google Scholar 

  51. Shegokar R, Müller RH. Nanocrystals. Industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm. 2010;399(1–2):129–39.

    Article  CAS  PubMed  Google Scholar 

  52. Lohan SB, Bauersachs S, Ahlberg S, et al. Ultra-small lipid nanoparticles promote the penetration of coenzyme Q10 in skin cells and counteract oxidative stress. Eur J Pharm Biopharm. 2015;89:201–7.

    Article  CAS  PubMed  Google Scholar 

  53. Abraham A. (in prep.), PlantCrystals for improved delivery of antioxidants, PhD-thesis, Philipps-Universität Marburg.

    Google Scholar 

  54. Griffin S, Tittikpina NK, Al-marby A, et al. Turning waste into value: nanosized natural plant materials of Solanum incanum L. and Pterocarpus erinaceus Poir with promising antimicrobial activities. Pharmaceutics. 2016;8(2):11.

    Article  PubMed Central  Google Scholar 

  55. Griffin S, Sarfraz M, Hartmann SF, et al. Resuspendable powders of lyophilized chalcogen particles with activity against microorganisms. Antioxidants (Basel). 2018;7(2):23.

    Article  Google Scholar 

  56. Griffin S, Sarfraz M, Farida V, et al. No time to waste organic waste. Nanosizing converts remains of food processing into refined materials. J Environ Manage. 2018;210:114–21.

    Article  PubMed  Google Scholar 

  57. Griffin S, Masood MI, Nasim MJ, et al. Natural nanoparticles. A particular matter inspired by nature. Antioxidants (Basel). 2017;7(1):3.

    Article  Google Scholar 

  58. Sinambela P, Egorov E, Löffler BM, et al. Anti-Aging rutin smartCrystals® for reduction of brown and red skin spots—an in vivo study, Menopause, Andropause, Anti-Aging-Kongress, Vienna/Austria, 6th–8th December; 2012.

    Google Scholar 

  59. Keck CM, Müller RH, Gohla S. Nanokristalle - innovatives Formulierungsprinzip für schwerlösliche Anti-Aging Wirkstoffe, Menopause, Andropause, Anti-Aging-Kongress, Vienna/Austria, 6th–8th December; 2007.

    Google Scholar 

  60. Sinambela P, Egorov E, Löffler BM, et al. Combination of rutin smartCrystals® and peptide-loaded liposomes for wrinkle reduction—an in vivo study, Menopause, Andropause, Anti-Aging-Kongress, Vienna/Austria, 6th–8th December; 2012.

    Google Scholar 

  61. Gerst M, Rostamizadeh K, Arntjen A, et al. ARTCrystal®-technology for improved dermal penetration of rutin nanocrystals, nanocrystals for improved antioxidant capacity of flavonoids, NutriOx 2014: Nutrition and Ageing, Metz/France, 1th–3th October; 2014.

    Google Scholar 

  62. Keck CM, Pyo SM, Jin N, et al. Rutin smartCrystals®—most effective anti-oxidant activity & skin penetration, Menopause, Andropause, Anti-Aging-Kongress, Vienna/Austria, 11th–13th December; 2014.

    Google Scholar 

  63. Jin N, Staufenbiel S, Keck CM, et al. SmartCrystals®—enhancement of drug penetration without penetration enhancer, Menopause, Andropause, Anti-Aging-Kongress, Vienna/Austria, 11th–13th December; 2014.

    Google Scholar 

  64. Keck CM, Monsuur F, Höfer HH, et al. SmartPearls®—new dermal injection-like delivery system without use of a needle, Menopause, Andropause, Anti-Aging-Kongress, Vienna/Austria, 11th–13th December; 2014.

    Google Scholar 

  65. Knauer J, Pyo SM, Keck CM, et al. Antioxidant activity of rutin—watersoluble derivatives vs. rutin smartCrystals®, Menopause, Andropause, Anti-Aging-Kongress, Vienna/Austria, 10th–12th December; 2015.

    Google Scholar 

  66. Pelikh O, Stahr P, Dietrich H, et al. Anti-aging actives for dermal application—size matters, Menopause, Andropause, Anti-Aging-Congress, Vienna/Austria, 6th–9th December; 2017.

    Google Scholar 

  67. Pelikh O, Stahr P, Dietrich H, et al. Anti-aging actives for dermal application—the vehicle is the key for efficacy, Menopause, Andropause, Anti-Aging-Congress, Vienna/Austria, 6th–9th December; 2017.

    Google Scholar 

  68. Pelikh O, Stahr P, Gerst M, et al. Nanocrystals for improved dermal drug delivery. Eur J Pharm Biopharm; 128:170–8.

    Article  CAS  PubMed  Google Scholar 

  69. Vogt A, Mandt N, Lademann J, et al. Follicular targeting—a promising tool in selective dermatotherapy. J Investig Dermatol Symp Proceed. 2005;10(3):252–5.

    Article  Google Scholar 

  70. Toll R, Jacobi U, Richter H, et al. Penetration profile of microspheres in follicular targeting of terminal hair follicles. J Invest Dermatol. 2004;123(1):168–76.

    Article  CAS  PubMed  Google Scholar 

  71. Vogt A, Hadam S, Deckert I, et al. Hair follicle targeting, penetration enhancement and Langerhans cell activation make cyanoacrylate skin surface stripping a promising delivery technique for transcutaneous immunization with large molecules and particle-based vaccines. Exp Dermatol. 2015;24(1):73–5.

    Article  CAS  PubMed  Google Scholar 

  72. Lademann J, Richter H, Schaefer UF, et al. Hair follicles—a long-term reservoir for drug delivery. Skin Pharmacol Physiol. 2006;19(4):232–6.

    Article  CAS  PubMed  Google Scholar 

  73. Blume-Peytavi U, Massoudy L, Patzelt A, et al. Follicular and percutaneous penetration pathways of topically applied minoxidil foam. Eur J Pharm Biopharm. 2010;76(3):450–3.

    Article  CAS  PubMed  Google Scholar 

  74. Knorr F, Lademann J, Patzelt A, et al. Follicular transport route—research progress and future perspectives. Eur J Pharm Biopharm. 2009;71(2):173–80.

    Article  CAS  PubMed  Google Scholar 

  75. Patzelt A, Knorr F, Blume-Peytavi U, et al. Hair follicles, their disorders and their opportunities. Drug Discov Today: Dis Mech. 2008;5(2):173–81.

    Article  Google Scholar 

  76. Blume-Peytavi U, Vogt A. Human hair follicle. Reservoir function and selective targeting. Br J Dermatol. 2011;165(2):13–7.

    Article  CAS  PubMed  Google Scholar 

  77. Raber AS, Mittal A, Schäfer J, et al. Quantification of nanoparticle uptake into hair follicles in pig ear and human forearm. J Control Release. 2014;179:25–32.

    Article  CAS  PubMed  Google Scholar 

  78. Wosicka H, Cal K. Targeting to the hair follicles. Current status and potential. J Dermatol Sci. 2010;57(2):83–9.

    Article  CAS  PubMed  Google Scholar 

  79. Otberg N, Patzelt A, Rasulev U, et al. The role of hair follicles in the percutaneous absorption of caffeine. Br J Clin Pharmacol. 2008;65(4):488–92.

    Article  CAS  PubMed  Google Scholar 

  80. Lauterbach A, Müller-Goymann CC. Comparison of rheological properties, follicular penetration, drug release, and permeation behavior of a novel topical drug delivery system and a conventional cream. Eur J Pharm Biopharm. 2014;88(3):614–24.

    Article  CAS  PubMed  Google Scholar 

  81. Lademann J, Knorr F, Richter H, et al. Hair follicles—an efficient storage and penetration pathway for topically applied substances. Summary of recent results obtained at the Center of Experimental and Applied Cutaneous Physiology, Charité - Universitätsmedizin Berlin, Germany. Skin Pharmacol Physiol. 2008;21(3):150–5.

    Article  CAS  PubMed  Google Scholar 

  82. European Parliament. Regulation (EC) No 1223/2009 of the European parliament and of the council of 30 November 2009 on cosmetic products. Off J Eur Union: L 342/59; 2009.

    Google Scholar 

  83. Keck CM, Müller RH. Nanotoxicological classification system (NCS)—a guide for the risk-benefit assessment of nanoparticulate drug delivery systems. Eur J Pharm Biopharm. 2013;84(3):445–8.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutics and Biopharmaceutics, Philipps-Universität Marburg, Robert-Koch-Str. 4, 35037, Marburg, Germany

    Olga Pelikh, Steffen F. Hartmann, Abraham M. Abraham & Cornelia M. Keck

Authors
  1. Olga Pelikh
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  2. Steffen F. Hartmann
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  3. Abraham M. Abraham
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  4. Cornelia M. Keck
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Corresponding author

Correspondence to Cornelia M. Keck .

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Editors and Affiliations

  1. vdlconsult , Hildesheim, Germany

    Jean Cornier

  2. Institut für Pharmazeutische Technologie und Biopharmazie, Philipps-Universität Marburg, Marburg, Germany

    Cornelia M. Keck

  3. Faculty of Natural Sciences, University of Technology DELFT, Crans-Montana, Switzerland

    Marcel Van de Voorde

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Pelikh, O., Hartmann, S.F., Abraham, A.M., Keck, C.M. (2019). Nanocrystals for Dermal Application. In: Cornier, J., Keck, C., Van de Voorde, M. (eds) Nanocosmetics. Springer, Cham. https://doi.org/10.1007/978-3-030-16573-4_8

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