Pharmaceutical Research

, Volume 22, Issue 11, pp 1887–1897 | Cite as

Solid Lipid Nanoparticles (SLN) and Oil-Loaded SLN Studied by Spectrofluorometry and Raman Spectroscopy

  • Katja Jores
  • Annekathrin Haberland
  • Siegfried Wartewig
  • Karsten MäderEmail author
  • Wolfgang Mehnert
Research Paper


Recently, colloidal dispersions made of mixtures from solid and liquid lipids have been described to overcome the poor drug loading capacity of solid lipid nanoparticles (SLN). It has been proposed that these nanostructured lipid carriers (NLC) are composed of oily droplets, which are embedded in a solid lipid matrix. High loading capacities and controlled release characteristics have been claimed. It is the objective of the present paper to investigate these new NLC particles in more detail to obtain insights into their structure.


Colloidal lipid dispersions were produced by high-pressure homogenization. Particle sizes were estimated by laser diffraction and photon correlation spectroscopy. The hydrophobic fluorescent marker nile red (NR) was used as model drug, and by fluorometric spectroscopy, the molecular environment (polarity) was elucidated because of solvatochromism of NR. The packaging of the lipid nanoparticles was investigated by Raman spectroscopy and by densimetry. The light propagation in lipid nanodispersions was examined by refractometry to obtain further insights into the nanostructural compositions of the carriers.


Fluorometric spectroscopy clearly demonstrates that NLC nanoparticles offer two nanocompartments of different polarity to accommodate NR. Nevertheless, in both compartments, NR experiences less protection from the outer water phase than in a nanoemulsion. In conventional SLN, lipid crystallization leads to the expulsion of the lipophilic NR from the solid lipid. Measurements performed by densimetry and Raman spectroscopy confirm the idea of intact glyceryl behenate lattices in spite of oil loading. The lipid crystals are not disturbed in their structure as it could be suggested in case of oil incorporation. Refractometric data reveal the idea of light protection because of incorporation of sensitive drug molecules in NLC.


Neither SLN nor NLC lipid nanoparticles did show any advantage with respect to incorporation rate compared to conventional nanoemulsions. The experimental data let us conclude that NLC lipid nanoparticles are not spherical solid lipid particles with embedded liquid droplets, but they are rather solid platelets with oil present between the solid platelet and the surfactant layer.

Key Words

colloidal carrier densimetry fluorometry nanoemulsion NLC Raman spectroscopy refractometry SLN solid lipid nanoparticles 



Katja Jores was supported by Deutsche Forschungsgemeinschaft (DFG).


  1. 1.
    Siekmann, B., Westesen, K. 1992Submicron-sized parenteral carrier systems based on solid lipidsPharm. Pharmacol. Lett.1123126Google Scholar
  2. 2.
    A. Dingler. Feste Lipid-Nanopartikel als kolloidale Wirkstoffträgersysteme zur dermalen Applikation, PhD Thesis, Berlin, 1998.Google Scholar
  3. 3.
    Müller, R. H., Mehnert, W., Lucks, J.-S., Schwarz, C., Mühlen, A. z., Weyhers, H., Freitas, C., Rühl, D. 1995Solid lipid nanoparticles (SLN)—An alternative colloidal carrier system for controlled drug deliveryEur. J. Biopharm.416269Google Scholar
  4. 4.
    Müller, R. H., Mäder, K., Gohla, S. 2000Solid lipid nanoparticles (SLN) for controlled drug delivery—A review of the state of the artEur. J. Biopharm.50161177CrossRefGoogle Scholar
  5. 5.
    Mehnert, W., Mäder, K. 2001Solid lipid nanoparticles: production, characterization and applicationsAdv. Drug Deliv. Rev.47165196CrossRefPubMedGoogle Scholar
  6. 6.
    Westesen, K., Bunjes, H., Koch, M. H. J. 1997Physicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potentialJ. Control. Release48223236CrossRefGoogle Scholar
  7. 7.
    Westesen, K., Siekmann, B. 1997Investigation of the gel formation of phospholipid-stabilized solid lipid nanoparticlesInt. J. Pharm.1513545CrossRefGoogle Scholar
  8. 8.
    Jenning, V., Thünemann, A. F., Gohla, S. H. 2000Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipidsInt. J. Pharm.199167177CrossRefPubMedGoogle Scholar
  9. 9.
    Müller, R. H., Radtke, M., Wissing, S. A. 2002Nanostructured lipid matrices for improved microencapsulation of drugsInt. J. Pharm.242121128CrossRefPubMedGoogle Scholar
  10. 10.
    Jenning, V., Mäder, K., Gohla, S. H. 2000Solid lipid nanoparticles (SLN™) based on binary mixtures of liquid and solid lipids: a 1H-NMR studyInt. J. Pharm.251521CrossRefGoogle Scholar
  11. 11.
    Hantzsch, A. 1922Über die Halochromie und “Solvatochromie” des Dibenzalacetons und einfacherer Ketone, sowie ihrer KetochlorideChem. Ber.55953979Google Scholar
  12. 12.
    Greenspan, P., Fowler, S. D. 1985Spectrofluorometric studies of the lipid probe nile redJ. Lipid Res.26781789PubMedGoogle Scholar
  13. 13.
    Bockisch, M. 1993Nahrungsfette und-öleUlmerStuttgartGoogle Scholar
  14. 14.
    A. Fischer-Carius. Untersuchungen an extrudierten und sphäronisierten Matrixpellets mit retardierter Wirkstofffreigabe, PhD Thesis, Berlin, 1998.Google Scholar
  15. 15.
    Bunjes, H., Westesen, K., Koch, M. H. J. 1996Crystallization tendency and polymorphic transitions in triglyceride nanoparticlesInt. J. Pharm.129159173CrossRefGoogle Scholar
  16. 16.
    ISO/DIS13320-11997Korngrößenanalyse—Leitfaden für LaserbeugungsverfahrenBeuth VerlagBerlin, Wein and ZürichGoogle Scholar
  17. 17.
    Jores, K., Mehnert, W., Drechsler, M., Bunjes, H., Johann, C., Mäder, K. 2004Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopyJ. Control. Release95217227CrossRefPubMedGoogle Scholar
  18. 18.
    Olbrich, C., Kayser, O., Lamprecht, A., Kneuer, C., Lehr, C. M., Müller, R. H. 2000Interactions of fluorescent solid lipid nanoparticles (SLN) with macrophage-like cells visualized by CLSMInternational Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical TechnologyAPV/APGIBerlin331332Google Scholar
  19. 19.
    Davis, M. M., Hetzer, H. B. 1966Titrimetric and equilibrium studies using indicators related to nile blue AAnal. Chem.38451461CrossRefGoogle Scholar
  20. 20.
    Siekmann, B., Westesen, K. 1994Thermoanalysis of the recrystallization process of melt-homogenized glyceride nanoparticlesColl. Surfaces, B3159175Google Scholar
  21. 21.
    Westesen, K., Bunjes, H. 1995Do nanoparticles prepared from lipids solid at room temperature always possess a solid lipid matrix?Int. J. Pharm.115129131CrossRefGoogle Scholar
  22. 22.
    S. Liedtke, K. Jores, W. Mehnert, K. Mäder, Possibilities of non-invasive physicochemical characterisation of colloidal drug carriers, 27th Intern. Symp. Control. Rel. Bioact. Mater., Vol. 27, Controlled Release Society, Paris (2000) pp. 1088–1089.Google Scholar
  23. 23.
    Udenfriend, S. 1962Fluorescence Assay in Biology and MedicineAcademic PressNew YorkGoogle Scholar
  24. 24.
    Wartewig, S., Neubert, R. 2002Nicht-invasive Analysenmethoden der Schwingungsspektroskopie in der pharmazeutischen ForschungPharm. Ind.64863869Google Scholar
  25. 25.
    Schrader, B. eds. 1995Infrared and Raman Spectroscopy, Methods and ApplicationsVCHWeinheimGoogle Scholar
  26. 26.
    Tandon, P., Förster, G., Neubert, R., Wartewig, S. 2000Phase transition in oleic acid as studied by X-ray diffraction and FT-Raman spectroscopyJ. Mol. Struct.524201215CrossRefGoogle Scholar
  27. 27.
    Mendelsohn, R., Moore, D. J. 1998Vibrational spectroscopic studies of lipid domains in biomembranes and model systemsChem. Phys. Lipids96141157CrossRefPubMedGoogle Scholar
  28. 28.
    Jores, K., Mehnert, W., Mäder, K. 2003Physicochemical investigations on solid lipid nanoparticles (SLN) and on oil-loaded solid lipid nanoparticles: A NMR- and ESR-studyPharm. Res.2012741283CrossRefPubMedGoogle Scholar
  29. 29.
    V. Jenning. Feste Lipid-Nanopartikel (SLN™) als Trägersystem für die dermale Applikation von Retinol: Wirkstoffinkorporation, -freisetzung und Struktur, PhD Thesis, Berlin, 1999.Google Scholar
  30. 30.
    Precht, D. 1988Fat crystal structure in cream and butterGarti, N.Sato, K. eds. Crystallization and Polymorphisms of Fats and Fatty AcidsMarcel Dekker Inc.New York305361Google Scholar
  31. 31.
    Jenning, V., Gohla, S. 2000Comparison of wax and glyceride solid lipid nanoparticles (SLN™)Int. J. Pharm.196219222PubMedGoogle Scholar
  32. 32.
    Jores, K., Mehnert, W., Mäder, K. 2003Physicochemical investigations on solid lipid nanoparticles (SLN) and on oil-loaded solid lipid nanoparticles: a nuclear magnetic resonance and electron spin resonance studyPharm. Res.2012741283CrossRefPubMedGoogle Scholar
  33. 33.
    C. Blümer K. Mäder. Isostatic Ultra High pressure effects on supercooled melts in colloidal triglyceride dispersions. Pharm. Res., accepted (2005).Google Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Katja Jores
    • 1
    • 2
  • Annekathrin Haberland
    • 3
  • Siegfried Wartewig
    • 4
  • Karsten Mäder
    • 2
    Email author
  • Wolfgang Mehnert
    • 1
  1. 1.Department of Pharmaceutical Technology, Institute of PharmacyFree University of BerlinBerlinGermany
  2. 2.Institute of Pharmaceutical Technology and BiopharmacyMartin Luther University Halle WittenbergHalle/SaaleGermany
  3. 3.Department of Pharmacology and Toxicology, Institute of PharmacyFree University of BerlinBerlinGermany
  4. 4.Institute of Applied DermatopharmacyHalle/SaaleGermany

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