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  • 1 Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, Office S.1, P-4200-150, Porto, Portugal
  • | 2 Department of Pharmaceutical Sciences, Mahatma Gandhi University, Cheruvandoor Campus, 686 631, Ettumanoor, Kerala, India
  • | 3 Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain
  • | 4 Institute of Nanoscience and Nanotechnology, University of Barcelona, Av. Joan XXIII s/n, 08028, Barcelona, Spain
  • | 5 Department of Endocrinology, Hospital de São João, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal
  • | 6 Institute of Biotechnology and Bioengineering, Centre of Genomics and Biotechnology University of Trás-os-Montes and Alto Douro (CGB-UTAD/IBB), P.O. Box 1013, 5001-801, Vila Real, Portugal
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Abstract

This article reports the thermodynamic changes of lipid nanoparticles (LN) upon delivery of lipophilic vitamin E derivatives to the skin. Skin penetration of α-tocopherol (α-T) and α-tocopherol acetate (α-Ta) into and across porcine ear skin was investigated in vitro using tape-stripping test in modified Franz diffusion cells. Wide angle X-ray scattering (WAXS) and differential scanning calorimetry (DSC) have been used to characterize the polymorphism of the solid matrix of LN before and after in vitro skin penetration assay. Cetyl palmitate LN with a loading capacity of 20% of vitamin E derivatives (with regard to the lipid matrix) have shown the typical β’ modification of waxes, with a crystallinity index (%CI) between 30 and 40%. Mean particle size and shelf life stability was assessed by static (laser diffractometry, LD) and dynamic (photon correlation spectroscopy, PCS) light scattering techniques. Submicron-sized LN were produced, i.e., 99% of LN showed a size below 600 nm immediately after production. A mean size between 180 and 350 nm (polydispersity index < 0.25) was obtained for LN stored at both 8 and 22 °C, and this size range was kept constant for at least 20 days of shelf life. Quantification of α-T and α-Ta in the skin using tape-stripping provided a 3.4-fold increase in the level of actives within the stratum corneum (SC) and 1.3-fold increase in the viable epidermis (VE). LN increased skin penetration of both actives, following a cumulative release during 8 h in modified Franz diffusion cells. The differences in the distribution levels observed between α-T and α-Ta when delivered via LN was due to the different thermodynamic activity of both actives, i.e., following increased partition coefficient of α-Ta into SC and VE, in comparison to α-T.

  • 1. Burton, GW, Ingold, KU. Vitamin E as in vitro and in vivo antioxidants. Ann N Y Acad Sci. 1989;570:722. .

  • 2. Kalka, K, Mukhtar, H, Turowski-Wanke, A, Merk, H. Biomelanin antioxidants in cosmetics: assessment based on inhibition of lipid peroxidation. Skin Pharmacol Appl Skin Physiol. 2000;13:143149. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Burgess, C. Topical vitamins. J Drugs Dermatol. 2008;7:s2s6.

  • 4. Van Haaften, RIM, Evelo, CTA, Penders, J, Eijnwachter, MPF, Haenen, GRMM, Bast, A. Inhibition of human glutathione S-transferase P1-1 by tocopherol and α-tocopherol derivatives. Biochim Biophys Acta. 2001;1548:2328. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Lam, PY, Yan, CW, Chiu, PY, Leung, HY, Ko, KM. 2011 Schisandrin B protects against solar irradiation-induced oxidative stress in rat skin tissue. Fitoterapia. 82:393400. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Doktorovova, S, Souto, EB. Nanostructured lipid carrier-based hydrogel formulations for drug delivery: a comprehensive review. Expert Opin Drug Deliv. 2009;6:165176. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Souto, EB, Muller, RH. Lipid nanoparticles: effect on bioavailability and pharmacokinetic changes. Handb Exp Pharmacol. 2010;197:115141. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Müller, RH, Mehnert, W, Souto, EB. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for dermal delivery Bronaugh, L, eds. Percutaneous absorption. New York: Marcel Dekker, Inc.; 2005 719738. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Souto, EB, Doktorovova, S. Chapter 6—solid lipid nanoparticle formulations pharmacokinetic and biopharmaceutical aspects in drug delivery. Methods Enzymol. 2009;464:105129. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Mehnert, W, Mäder, K. Solid lipid nanoparticles—production, characterization and applications. Adv Drug Deliv Rev. 2001;47:165196. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11. Müller, RH, Mäder, K, Gohla, S. Solid lipid nanoparticles (SLN) for controlled drug delivery—a review of the state of art. Eur J Pharm Biopharm. 2000;50:161177. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Müller, RH, Radtke, M, Wissing, SA. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv Drug Deliv Rev. 2002;54:S131S155. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Dingler, A, Gohla, S. Production of solid lipid nanoparticles (SLN): scaling up feasibilities. J Microencapsul. 2002;19:1116. .

  • 14. Wissing, SA, Lippacher, A, Müller, RH. Investigations on the occlusive properties of solid lipid nanoparticles (SLN). J Cosmet Sci. 2001;52:313324.

    • Search Google Scholar
    • Export Citation
  • 15. Wissing, SA, Müller, RH. A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles. Int J Cosmet Sci. 2001;23:233243. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Wissing, SA, Müller, RH. 2002 The influence of the crystallinity of lipid nanoparticles on their occlusive properties. Int J Pharm. 242:377379. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17. Pilgram, GSK, van Pelt, AME, Bouwstra, JA, Koerten, HK. Electron diffraction provides new information on human stratum corneum lipid organization studied in relation to depth and temperature. J Investig Dermatol. 1999;113:403409. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Gonzalez-Mira, E, Nikolic, S, Garcia, ML, Egea, MA, Souto, EB, Calpena, AC. Potential use of nanostructured lipid carriers for topical delivery of flurbiprofen. J Pharm Sci. 2011;100:242251. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19. Freitas, C, Müller, RH. Correlation between long-term stability of solid lipid nanoparticles (SLN™) and crystallinity of the lipid phase. Eur J Pharm Biopharm. 1999;47:125132. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20. Egorova, EM. The validity of the Smoluchowski equation in electrophoretic studies of lipid membranes. Electrophoresis. 1994;15:11251131. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21. Martins, S, Silva, AC, Ferreira, DC, Souto, EB. Improving oral absorption of Salmon calcitonin by trimyristin lipid nanoparticles. J Biomed Nanotechnol. 2009;5:7683. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22. Weyhers H . Feste Lipid Nanopartikel (SLN) für die gewebsspezifische Arzneistoffapplikation, Herstellung, Charakterisierung oberflächenmodifizierter Formulierungen. PhD Thesis, Freie Universität Berlin, Berlin; 1995.

    • Search Google Scholar
    • Export Citation
  • 23. Nielsen, PB, Müllertz, A, Norling, T, Kristensen, HG. The effect of α-tocopherol on the in vitro solubilisation of lipophilic drugs. Int J Pharm. 2001;222:217224. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24. Souto, EB, Müller, RH. SLN and NLC for topical delivery of ketoconazole. J Microencapsul. 2005;22:501510. .

  • 25. Alvarez-Roman, R, Naik, A, Kalia, YN, Guy, RH, Fessi, H. Skin penetration and distribution of polymeric nanoparticles. J Control Release. 2004;99:5362. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Short, SM, Paasch, BD, Turner, JH, Weiner, N, Daugherty, AL, Mrsny, RJ. Percutaneous absorption of biologically-active interferon-gamma in a human skin graft-nude mouse model. Pharm Res. 1996;13:10201027. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Short, SM, Rubas, W, Paasch, BD, Mrsny, RJ. Transport of biologically active interferon-gamma across human skin in vitro. Pharm Res. 1995;12:11401145. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. Downing, DT, Strauss, JS. On the mechanism of sebaceous secretion. Arch Dermatol Res. 1982;272:343349. .