Abstract
Purpose. Assessment of the in vitro cytotoxicity of solid lipid nanoparticles (SLNs) as a function of lipid matrix (Dynasan 114, Compritol ATO 888), and stabilizing surfactant (poloxamers, Tween 80, soya lecithin, and sodium dodecyl sulphate). Comparison with other colloidal carriers should determine their potential use in the clinic.
Methods. SLNs were produced by high pressure homogenisation. Cytotoxicity was assessed by measuring the viability of HL60 cells and human granulocytes after incubation with SLNs. Particle internalisation was quantified by chemiluminescence measurements.
Results. The nature of the lipid had no effect on viability; distinct differences were found for the surfactants. Binding to the SLN surface reduced markedly the cytotoxic effect of the surfactants, e.g., up to a factor of 65 for poloxamer 184. The permanent HL60 cell line— differentiated from cells with granulocyte characteristics by retinoic acid treatment—yielded results identical to freshly isolated human granulocytes. In general, the SLNs showed a lower cytotoxicity compared to polyalkylcyanoacrylate and polylactic/glycolic acid (PLA/ GA) nanoparticles.
Conclusions. Because the results are identical when using human granulocytes, differentiated HL60 cells can be used as an easily accessible in vitro test system for i.v. injectable SLN formulations. The SLNs appear suitable as a drug carrier system for potential intravenous use due to their very low cytotoxicityin vitro.
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REFERENCES
P. Speiser. Lipidnanopellets als Trägersystem für Arzneimittel zur peroralen Anwendung. European Patent EP 0167825 (1990).
M. R. Gasco. Solid lipid microspheres having a narrow size distribution and method for producing them. European Patent 0526666 A1 (1991).
R. H. Müller, W. Mehnert, J. S. Lucks, C. Schwarz, A. zur Mühlen, H. Weyhers, C. Freitas, and D. Rühl. Eur. J. Pharm. Biopharm. 41(1):62–69 (1995).
S. Maaßen. Solid lipid nanoparticles (SLN)—Vergleichende Phagozytose-und Zytotoxizitätsuntersuchungen an humanen Granulozyten. PhD thesis University of Kiel (1994).
H. Weyhers, S. Ehlers, W. Mehnert, H. Hahn, and R. H. Müller. Proceed. 1st World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology (APGI, APV) Budapest: 489–490 (1995).
T. R. Breitmann, S. W. Selonick, and S. J. Collins. Proc. Natl. Acad. Sci. USA 77:2936–2940 (1980).
L. T. Williams, R. Snyderman, M. C. Pike, and R. J. Lefkowitz. Proc. Natl. Acad. Sci. USA 74:1204 (1977).
S. Rudt, and R. H. Müller. Int. J. Pharm. 99:1–6 (1993).
C. Lherm, R. H. Müller, F. Pusieux, and P. Couvreur. Int. J. Pharm. 84:13–22 (1992).
P. Couvreur. CRC Crit. Rev. Ther. Drug Carrier Systems 5:1–20 (1988).
V. Lenaerts, J. F. Nagelkerke, T. J. C. Van Berkel, P. Couvreur, L. Grislain, M. Roland, and P. Speiser. J. Pharm. Sci. 73:980–982 (1984).
J. Kattan, J. P. Droz, P. Couvreur, J. P. Marino, A. Boutan-Laroze, P. Rougier, P. Brault, H. Vranckx, J. M. Grognet, X. Morge, H. Sancho-Garnier. Invest. New Drug, 10:191–199 (1992)
F. Brasseur, A. Biernacki, V. Lenaerts, L. Galanti, P. Couvreur, C. Deckers, M. Roland. Proc. 3rd Int: Conf. Pharm. Technol. 2:194–202 (1983)
A. Bräuer. Hepatozyten-Zellkulturen—in vitro-Testsystem zur Optimierung neuer Arzneiformulierungen. PhD thesis University of Kiel (1991)
F. Koosha, R. H. Müller, S. S. Davis, and M. C. Davies. J. Control. Rel. 9:145–157 (1989).
S. Rudt, and R. H. Müller. J. Control. Rel. 25:51–59 (1993).
A. Bräuer, C. Aschmann, and R. H. Müller. Arch Pharm. 322:755 (1989).
E. M. Gipps, P. Groscurth, J. Kreuter, and P. P. Kreuter. Int. J. Pharm. 40:23–31 (1987)
A. Bräuer, C. Lherm, P. Couvreur, and R. H. Müller. Acta Pharm. Technol. 36:33S (1990).
S. Rudt. Untersuchungen zur in vitro Phagozytose und zur Cytotoxizität von Arzneistoffträgersystemen für die parenterale Applikation. PhD thesis University of Kiel (1992).
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Müller, R.H., Rühl, D., Runge, S. et al. Cytotoxicity of Solid Lipid Nanoparticles as a Function of the Lipid Matrix and the Surfactant. Pharm Res 14, 458–462 (1997). https://doi.org/10.1023/A:1012043315093
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DOI: https://doi.org/10.1023/A:1012043315093