Abstract
Purpose. To investigate the influence of fluorescent labelling of polystyrene particles on phagocytic uptake, surface hydrophobicity and protein adsorption.
Methods. Phagocytic uptake was analysed using chemiluminescence. Hydrophobicity was quantified by adsorption measurements of a hydrophobic dye. Protein adsorption was evaluated by two-dimensional electrophoresis.
Results. Commercially available fluorescently labelled particles showed marked differences when compared to unlabelled particles: phagocytic uptake and surface hydrophobicity of labelled particles were diminished. Also the plasma protein adsorption pattern was found to be different from the unlabelled particles: for example, the amount of fibrinogen adsorbed was strongly reduced on the labelled particles. On the other hand, some unknown proteins could be detected on the fluorescently marked particles. In contrast, plain polystyrene particles and labelled ones could be successfully synthesised by Paulke which did not show any considerable differences in phagocytic uptake, surface hydrophobicity and protein adsorption. Polysorbate 20 added as stabilizer to particle suspensions led to completely different behaviour of the particles: the particles showed altered protein adsorption patterns, dominated by immunoglobulins and especially by apolipoproteins. Furthermore, these particles were not phagocytized at all.
Conclusions. Surface hydrophobicity and phagocytic uptake in vitro as well as the interactions with plasma proteins of commercially available polystyrene particles were strongly affected by fluorescent labelling. Particles synthesised by Paulke remained unchanged after labelling. The results show the importance of thorough surface characterization for using particles in test systems in vitro and in vivo.
Similar content being viewed by others
REFERENCES
J. N. Weinstein and L. D. Leserman. Pharm. Ther. 24:207–215 (1984).
L. Illum and S. S. Davis. J. Parent. Sci. Tech. 36:242–253 (1982).
E. Tomlinson and J. G. McVie. Pharm. Int. 4:281–287 (1983).
S. S. Davis, S. Douglas, L. Illum, P. D. E. Mak, and R. H. Müller. In G. Gregoriadis, J. Senior and G. Poste (eds.), Targeting of drugs with synthetic systems, Plenum Press, New York, 1986, pp. 123–146.
H. Weyhers. Feste Lipid Nanopartikel (SLN) für die gewebsspezifische Arzneistoffapplikation, Ph.D. thesis, The Free University of Berlin, 1995.
R. H. Müller. Colloidal carriers for controlled drug delivery and targeting, Wissenschaftliche Verlagsgesellschaft, Stuttgart, CRC Press, Boca Raton, 1991.
S. Rudt. Untersuchungen zur in vitro-Phagozytose und zur Cytotoxizität von Arzneistoff-Trägersystemen für die parenterale Applikation, Ph.D. thesis, University of Kiel, 1992.
S. Maaßen. Solid Lipid nanoparticles (SLN)-Phagozytose-und Toxizitätsuntersuchungen an Humangranulozyten, Ph.D. thesis, University of Kiel, 1994.
T. Blunk. Plamaproteinadsorption aufkolloidalen Arzneistoffträgern, Ph.D. thesis, University of Kiel, 1994.
T. Blunk, D. F. Hochstrasser, J.-C. Sanchez, B. W. Müller, and R. H. Müller. Electrophoresis 14:1382–1387 (1993).
R. H. Müller and S. Heinemann. In R. Gurny and H. E. Junginger (eds.), Bioadhesion-Possibilities and Future Trends, Wissenschaftliche Verlagsgesellschaft, Stuttgart, 1989, pp. 202–213.
A. Kotera, F. Furusawa, and Y. Takeda. Kolloid Z. Z. Polymere 239:677–681 (1970).
J. W. Goodwin, J. Hearn, C.-C. Ho, and R. H. Ottewill. Colloid. Polymer. Sci. 252:464–471 (1974).
S. J. Collins, F. W. Ruscetti, R. E. Gallagher, and R. C. Gallo. Proc. Natl. Acad. Sci. USA 75:2458–2462 (1978).
Y. Honma, K. Takenaga, T. Kasukabe, and M. Hozumi. Biochem. Biophys. Res. Comm. 95:507–512 (1980).
E. Ka-Wai Hui and B. Yat-Ming Yung. FEBS 318:193–199 (1993).
T. R. Breitmann, S. W. Selonick, and S. J. Collins. Proc. Natl. Acad. Sci. USA 77:2936–2940 (1980).
P. Newburger, M. Chovanic, J. Greenberger, and H. Cohen. J. Cell. Biol. 82:315–322 (1979).
S. Rudt and R. H. Müller. J. Controll. Rel. 25:51–59 (1993).
S. Rudt and R. H. Müller. Int. J. Pharm. 99:1–6 (1993).
S. Rudt and R. H. Müller. J. Controll. Rel. 22:263–272 (1992).
D. F. Hochstrasser, M. G. Harrington, A.-C. Hochstrasser, M. J. Miller, and C. R. Merril. Anal. Biochem. 173:424–435 (1988).
R. D. Appel, D. F. Hochstrasser, M. Funk, J. R. Vargas, C. Pellegrini, A. F. Muller, and J. R. Scherrer. Electrophoresis 12:722–735 (1991).
O. Golaz, G. J. Hughes, S. Frutiger, N. Paquet, A. Bairoch, C. Pasquali, J.-C. Sanchez, J.-D. Tissot, R. D. Appel, C. Walzer, L. Balant, and D. F. Hochstrasser. Electrophoresis 14:1223–1231 (1993).
N. L. Anderson and N. G. Anderson. Electrophoresis 12:883–906 (1991).
G. Lukowski, R. H. Müller, B. W. Müller, and M. Dittgen. Int. J. Pharm. 84:23–31 (1992).
H. Hedeman, M. Lück, T. Blunk, S. Frokjaer, and R. H. Müller. Clin. Nutr. (in press).
C. J. Van Oss, C. F. Gillman, and A. W. Neumann. Phagocytic engulfment and cell adhesiveness as cellular surface phenomena, Marcel Decker, New York, 1975.
C. J. Van Oss, D. R. Absolom, and A. W. Neumann. Ann. N. Y. Acad. Sci. 416:332–350 (1984).
I. M. Roitt et al. Kurzes Lehrbuch der Immunologie, Georg Thieme Verlag, Stuttgart, 1991.
E. Brynda, N. A. Cepalova, and M. Stol. J. Biomed. Mater. Res. 18:685–693 (1984).
R. Alyautdin, D. Gothier, V. Petrov, D. Kharkevich, and J. Kreuter. Eur. J. Pharm. Biopharm. 41(1):44–48 (1995).
J. Lee, P. A. Martic, and J. S. Tan. J. Colloid Interf. Sci. 131:252–266 (1989).
S. I. Jeon, J. H. Lee, J. D. Andrade, and P. G. De Gennes. J. Colloid Interf. Sci. 142:149–158 (1991).
R. H. Müller and S. Rudt. Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 18:219 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Müller, R.H., Rühl, D., Lück, M. et al. Influence of Fluorescent Labelling of Polystyrene Particles on Phagocytic Uptake, Surface Hydrophobicity, and Plasma Protein Adsorption. Pharm Res 14, 18–24 (1997). https://doi.org/10.1023/A:1012043131081
Issue Date:
DOI: https://doi.org/10.1023/A:1012043131081