Purpose
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.
Methods
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.
Results
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.
Conclusion
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.
Similar content being viewed by others
References
B. Siekmann K. Westesen (1992) ArticleTitleSubmicron-sized parenteral carrier systems based on solid lipids Pharm. Pharmacol. Lett. 1 123–126
A. Dingler. Feste Lipid-Nanopartikel als kolloidale Wirkstoffträgersysteme zur dermalen Applikation, PhD Thesis, Berlin, 1998.
R. H. Müller W. Mehnert J.-S. Lucks C. Schwarz A. z. Mühlen H. Weyhers C. Freitas D. Rühl (1995) ArticleTitleSolid lipid nanoparticles (SLN)—An alternative colloidal carrier system for controlled drug delivery Eur. J. Biopharm. 41 62–69
R. H. Müller K. Mäder S. Gohla (2000) ArticleTitleSolid lipid nanoparticles (SLN) for controlled drug delivery—A review of the state of the art Eur. J. Biopharm. 50 161–177 Occurrence Handle10.1016/S0939-6411(00)00087-4
W. Mehnert K. Mäder (2001) ArticleTitleSolid lipid nanoparticles: production, characterization and applications Adv. Drug Deliv. Rev. 47 165–196 Occurrence Handle10.1016/S0169-409X(01)00105-3 Occurrence Handle11311991
K. Westesen H. Bunjes M. H. J. Koch (1997) ArticleTitlePhysicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potential J. Control. Release 48 223–236 Occurrence Handle10.1016/S0168-3659(97)00046-1
K. Westesen B. Siekmann (1997) ArticleTitleInvestigation of the gel formation of phospholipid-stabilized solid lipid nanoparticles Int. J. Pharm. 151 35–45 Occurrence Handle10.1016/S0378-5173(97)04890-4
V. Jenning A. F. Thünemann S. H. Gohla (2000) ArticleTitleCharacterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids Int. J. Pharm. 199 167–177 Occurrence Handle10.1016/S0378-5173(00)00378-1 Occurrence Handle10802410
R. H. Müller M. Radtke S. A. Wissing (2002) ArticleTitleNanostructured lipid matrices for improved microencapsulation of drugs Int. J. Pharm. 242 121–128 Occurrence Handle10.1016/S0378-5173(02)00180-1 Occurrence Handle12176234
V. Jenning K. Mäder S. H. Gohla (2000) ArticleTitleSolid lipid nanoparticles (SLN™) based on binary mixtures of liquid and solid lipids: a 1H-NMR study Int. J. Pharm. 25 15–21 Occurrence Handle10.1016/S0378-5173(00)00462-2
A. Hantzsch (1922) ArticleTitleÜber die Halochromie und “Solvatochromie” des Dibenzalacetons und einfacherer Ketone, sowie ihrer Ketochloride Chem. Ber. 55 953–979
P. Greenspan S. D. Fowler (1985) ArticleTitleSpectrofluorometric studies of the lipid probe nile red J. Lipid Res. 26 781–789 Occurrence Handle4031658
M. Bockisch (1993) Nahrungsfette und-öle Ulmer Stuttgart
A. Fischer-Carius. Untersuchungen an extrudierten und sphäronisierten Matrixpellets mit retardierter Wirkstofffreigabe, PhD Thesis, Berlin, 1998.
H. Bunjes K. Westesen M. H. J. Koch (1996) ArticleTitleCrystallization tendency and polymorphic transitions in triglyceride nanoparticles Int. J. Pharm. 129 159–173 Occurrence Handle10.1016/0378-5173(95)04286-5
InstitutionalAuthorNameISO/DIS13320-1 (1997) Korngrößenanalyse—Leitfaden für Laserbeugungsverfahren Beuth Verlag Berlin, Wein and Zürich
K. Jores W. Mehnert M. Drechsler H. Bunjes C. Johann K. Mäder (2004) ArticleTitleInvestigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy J. Control. Release 95 217–227 Occurrence Handle10.1016/j.jconrel.2003.11.012 Occurrence Handle14980770
C. Olbrich O. Kayser A. Lamprecht C. Kneuer C. M. Lehr R. H. Müller (2000) Interactions of fluorescent solid lipid nanoparticles (SLN) with macrophage-like cells visualized by CLSM International Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology APV/APGI Berlin 331–332
M. M. Davis H. B. Hetzer (1966) ArticleTitleTitrimetric and equilibrium studies using indicators related to nile blue A Anal. Chem. 38 451–461 Occurrence Handle10.1021/ac60235a020
B. Siekmann K. Westesen (1994) ArticleTitleThermoanalysis of the recrystallization process of melt-homogenized glyceride nanoparticles Coll. Surfaces, B 3 159–175
K. Westesen H. Bunjes (1995) ArticleTitleDo nanoparticles prepared from lipids solid at room temperature always possess a solid lipid matrix? Int. J. Pharm. 115 129–131 Occurrence Handle10.1016/0378-5173(94)00347-8
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.
S. Udenfriend (1962) Fluorescence Assay in Biology and Medicine Academic Press New York
S. Wartewig R. Neubert (2002) ArticleTitleNicht-invasive Analysenmethoden der Schwingungsspektroskopie in der pharmazeutischen Forschung Pharm. Ind. 64 863–869
B. Schrader (Eds) (1995) Infrared and Raman Spectroscopy, Methods and Applications VCH Weinheim
P. Tandon G. Förster R. Neubert S. Wartewig (2000) ArticleTitlePhase transition in oleic acid as studied by X-ray diffraction and FT-Raman spectroscopy J. Mol. Struct. 524 IssueID27 201–215 Occurrence Handle10.1016/S0022-2860(00)00378-1
R. Mendelsohn D. J. Moore (1998) ArticleTitleVibrational spectroscopic studies of lipid domains in biomembranes and model systems Chem. Phys. Lipids 96 141–157 Occurrence Handle10.1016/S0009-3084(98)00085-1 Occurrence Handle9871985
K. Jores W. Mehnert K. Mäder (2003) ArticleTitlePhysicochemical investigations on solid lipid nanoparticles (SLN) and on oil-loaded solid lipid nanoparticles: A NMR- and ESR-study Pharm. Res. 20 1274–1283 Occurrence Handle10.1023/A:1025065418309 Occurrence Handle12948026
V. Jenning. Feste Lipid-Nanopartikel (SLN™) als Trägersystem für die dermale Applikation von Retinol: Wirkstoffinkorporation, -freisetzung und Struktur, PhD Thesis, Berlin, 1999.
D. Precht (1988) Fat crystal structure in cream and butter N. Garti K. Sato (Eds) Crystallization and Polymorphisms of Fats and Fatty Acids Marcel Dekker Inc. New York 305–361
V. Jenning S. Gohla (2000) ArticleTitleComparison of wax and glyceride solid lipid nanoparticles (SLN™) Int. J. Pharm. 196 219–222 Occurrence Handle10699722
K. Jores W. Mehnert K. Mäder (2003) ArticleTitlePhysicochemical investigations on solid lipid nanoparticles (SLN) and on oil-loaded solid lipid nanoparticles: a nuclear magnetic resonance and electron spin resonance study Pharm. Res. 20 1274–1283 Occurrence Handle10.1023/A:1025065418309 Occurrence Handle12948026
C. Blümer K. Mäder. Isostatic Ultra High pressure effects on supercooled melts in colloidal triglyceride dispersions. Pharm. Res., accepted (2005).
Acknowledgment
Katja Jores was supported by Deutsche Forschungsgemeinschaft (DFG).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jores, K., Haberland, A., Wartewig, S. et al. Solid Lipid Nanoparticles (SLN) and Oil-Loaded SLN Studied by Spectrofluorometry and Raman Spectroscopy. Pharm Res 22, 1887–1897 (2005). https://doi.org/10.1007/s11095-005-7148-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-005-7148-5