Investigation on Particle Self-Assembly in Solid Lipid-Based Colloidal Drug Carrier Systems
Purpose. The effect of spontaneous particle self-assembly into stack-like structures occurring in dispersions of melt-homogenized tripalmitin nanocrystals (solid lipid nanoparticles; SLNs) was studied in dependence of lipid concentration, stabilizer type, stabilizer concentration, and particle size.
Methods. Tripalmitin nanosuspensions with concentrations ranging from 20 to 200 mg/g were prepared by high-pressure melt homogenization. The formulations were characterized by synchrotron small-angle X-ray scattering (SAXS), photon correlation spectroscopy (PCS), and freeze-fracture transmission electron microscopy (TEM).
Results. Dispersions of partly self-assembled particles could be derived both with anionic or cationic surfactants. Particle self-assemblies were observed in such formulations when the tripalmitin concentration exceeds 40 mg/g. Further increase of the lipid concentration enhances particle self-assembly. The tendency to form self-assemblies is also influenced by the particle shape. The interparticle distances in stacked lamellae are determined by the tripalmitin concentration and by the surfactant concentration.
Conclusions. Parallel alignment of tripalmitin nanoplatelets is a completely reversible and concentration-dependent effect that can be attributed to the overlap of the exclusion volumes of the anisometric particles. The usefulness of this effect might be explored for the formulation of drug delivery systems.
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- 1.K. Westesen and B. Siekmann. Biodegradable colloidal drug carrier systems based on solid lipids. In S. Benita (ed.), Microencapsulation, Marcel Dekker, New York, 1996, pp.213-258.Google Scholar
- 2.K. Westesen. Novel lipid-based colloidal dispersions as potential drug administration systems—expectations and reality. Colloid Polym. Sci. 278:608-618 (2000).Google Scholar
- 3.R. H. Müller, K. Mäder, and S. Gohla. Solid lipid nanoparticles (SLN) for controlled drug delivery—a review of the state of art. Eur. J. Pharm. Biopharm. 50:161-177 (2000).Google Scholar
- 4.K. Westesen, B. Siekmann, and M. H. J. Koch. Investigation on the physical state of lipid nanoparticles by synchrotron radiation X-ray diffraction. Int. J. Pharm. 93:189-199 (1993).Google Scholar
- 5.W. Schütze and C. C. Müller-Goymann. Phase transformation of a liposomal dispersion into a micellar solution induced by drug-loading. Pharm. Res. 15:538-543 (1998).Google Scholar
- 6.H. Bunjes, M. H. J. Koch, and K. Westesen. Effect of particle size on colloidal solid triglycerides. Langmuir 16:5234-5241 (2000).Google Scholar
- 7.G. Lukowski, J. Kasbohm, P. Pflegel, A. Illing, and H. Wulff. Crystallographic investigation of cetylpalmitate solid lipid nanoparticles. Int. J. Pharm. 196:201-205 (2000).Google Scholar
- 8.T. Unruh, K. Westesen, P. Boesecke, P. Lindner, and M. H. J. Koch. Self-assembly of triglyceride nanocrystals in suspension. Langmuir 18:1796-1800 (2002).Google Scholar
- 9.M. H. J. Koch, I. Bordas. X-ray diffraction and scattering on disordered systems using synchrotron radiation. Nucl. Instrum. Meth. 208:461-469 (1983).Google Scholar
- 10.C. J. Boulin, R. Kempf, A. Gabriel, and M. H. J. Koch. Data acquisition-systems for linear and area x-ray-detectors using delay-line readout. Nucl. Instrum. Meth. A269:312-320 (1988).Google Scholar
- 11.A. Gabriel. Position-sensitive x-ray detector. Rev. Sci. Instrum. 48:1303-1305 (1977).Google Scholar
- 12.C. de Raad Iseli. T. Reimann, F. Golding, C. Boulin, A. Epstein, E. Beloeuvre, A. Gabriel, and M. H. J. Koch. A data acquisition system for gas proportional detectors with delay line readout based onspace-time-space conversion. Nucl. Instrum. Meth. A467:1152-1155 (2001).Google Scholar
- 13.R. J. Hunter. Foundations of Colloid Science, Vol. II, Clarendon Press, Oxford, 1989, pp 827-834.Google Scholar
- 14.S. Jogun and C. F. Zukoski. Rheology of dense suspensions of plateletlike particles. J. Rheol. 40:1211-1232 (1996).Google Scholar
- 15.A. van Langevelde, K. van Maalsen, F. Hollander, R. Peschar, and H. Schenk. Structure of mono-acid even-numbered β-triacylglycerols. Acta Cryst. B55:114-122 (1999).Google Scholar
- 17.H. Bunjes, M. H. J. Koch, and K. Westesen. Influence of emulsifiers on the crystallization of solid lipid nanoparticles. J. Pharm. Sci. 92:1509-1520 (2003).Google Scholar