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Phagocytosis of Nanoparticles by Human Immunodeficiency Virus (HlV)-Infected Macrophages: A Possibility for Antiviral Drug Targeting

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Abstract

Human monocytes/macrophages (MO/MAC) were isolated from peripheral blood and cultivated on hydrophobic Teflon membranes. This culture system is suitable for HIV infection of MO/MAC in vitro. After transfer into 24-well plates the mature macrophages (infected or uninfected) were used for measurements of phagocytosis. The uptake of different, radioactively labeled nanoparticles (NP) made of polyalkylcyanoacrylate, polymethylmethacrylate (PMMA), and human serum albumin (HSA) by the macrophages was determined. In addition, the influence on phagocytosis of size and composition, concentration, and surface of the NP was studied. Further, macrophages of different state of activation were tested. NP made of polyhexylcyanoacrylate (PHCA) or human serum albumin with a diameter of about 200 nm were found most useful for targeting antiviral substances such as azidotymidine to macrophages. Cells infected in vitro with HIV-1D117/III, a monocytotropic HIV isolate from a perinatally infected child, possessed an even higher phago-cytotic activity than noninfected cells. Macrophages isolated from HIV-infected patients also showed good incorporation of NP. Thus, the concept of a specific targeting of antiviral substances to macrophages in HIV-infected individuals appears quite promising.

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REFERENCES

  1. R. B. Johnston. Monocytes and macrophages. N. Engl. J. Med. 318:747 (1988).

    Google Scholar 

  2. R. van Furth. Phagocytic cells. Development and distribution of mononuclear phagocytes in normal steady state and inflammation. In J. Gallen, M. Golstein, and R. Snyderman (eds.), Inflammation, Raven Press, New York, 1988, p. 281.

    Google Scholar 

  3. R. Andreesen, K. J. Bross, J. Osterholz, and F. Emmrich. Human macrophage maturation and heterogeneity: Analysis with a newly generated set of monoclonal antibodies to differentiation antigens. Blood 67:1257–1264 (1986).

    Google Scholar 

  4. C. Scheibenbogen, W. Brugger, C. Rordorf, and R. Andreesen. Developmental regulation and stimulus specificity of cytokine release by human macrophages. Exp. Cell Biol. 57:118 (1989).

    Google Scholar 

  5. H. E. Gendelmann, J. M. Orenstein, M. A. Martin, C. Ferrua, R. Mitra, T. Phipps, L. A. Wahl, H. C. Lane, A. S. Fauci, D. S. Burke, D. Skillman, and M. S. Meltzer. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating-factor-1-treated monocytes. J. Exp. Med. 167:1428–1441 (1988).

    Google Scholar 

  6. H. Kühnel, H. von Briesen, U. Dietrich, M. Adamski, D. Mix, L. Biesert, R. Kreutz, A. Immelmann, C. Meichsner, R. Andreesen, H. Gelderblom, and H. Rübsamen-Waigmann. Molecular cloning of two West African human deficiency virus type 2 isolates that replicate well in macrophages: a Gambian isolate, from a patient with neurologic acquired immunodeficiency syndrome, and a highly divergent Ghanian isolate. Proc. Natl. Acad. Sci. (Wash.) 86:2383–2387 (1989).

    Google Scholar 

  7. H. von Briesen, R. Andreesen, R. Esser, W. Brugger, C. Meichsner, K. Becker, and H. Rübsamen-Waigmann. Infection of monocytes/macrophages by HIV in vitro. Res. Virol. 141:225–231 (1990).

    Google Scholar 

  8. S. Roy and M. A. Wainberg. Role of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS). J. Leukocyte Biol. 43:91–97 (1988).

    Google Scholar 

  9. M. S. Meltzer, D. R. Skillmann, and H. E. Gendelmann. Macrophages and the human immunodeficiency virus. Immunol. Today 6:217–224 (1990).

    Google Scholar 

  10. J. Kreuter, U. Taeuber, and V. Illi. Distribution and elimination of polymethylmethacrylate nanoparticles after injection in rats and mice. J. Pharm. Sci. 68:1443–1447 (1979).

    Google Scholar 

  11. P. G. Waser, U. Müller, J. Kreuter, S. Berger, K. Munz, E. Kaiser, and B. Pfluger. Localisation of colloidal particles (liposomes, hexylcyanoacrylate nanoparticles and albumin nanoparticles) by histology and autoradiography in mice. Int. J. Pharm. 39:213–227 (1987).

    Google Scholar 

  12. J. Kreuter, W. Stille, and S. Tröster. Pharmazeutische Zubereitung zur Behandlung von Infektionen mit HIV-Viren und damit verbundenen Begleitinfektionen. Deutsches Patent No. P37/7 406.1 (1987).

  13. D. L. Munz, R. Standke, and G. Hör. Measurement of phagocytic and proteolytic function of macrophages in liver, spleen and bone marrow. In P. H. Cox (ed.), Progress in Radiopharmacology 2:261–266 (1981).

  14. G. Hör, D. L. Munz, J. Brandhorst, F. D. Maul, and R. P. Baum. Scintigraphy of lymphokinetics and lymphatic neoplasia. In C. Winkler (ed.), Nuclear Medicine in Clinical Oncology, Springer-Verlag, Berlin, Heidelberg, 1986.

    Google Scholar 

  15. D. Leu, B. Manthey, J. Kreuter, P. Speiser, and P. Deluca. Distribution and elimination of coated polymethylmethacrylate nanoparticles after intravenous injection in rats. J. Pharm. Sci. 73:1433–1437 (1984).

    Google Scholar 

  16. S. D. Tröster, U. Müller, and J. Kreuter. Modification of the body distribution of polymethylmethacrylate nanoparticles in rats by coating with surfactants. Int. J. Pharm. 61:85–100 (1990).

    Google Scholar 

  17. R. Andreesen, J. Picht, and G. W. Lör. Primary cultures of human blood-borne macrophages grown on hydrophobic teflon membranes. J. Immunol. Methods 56:295–304 (1983).

    Google Scholar 

  18. D. S. Burke and R. R. Redfield. Classification of infections with human immunodeficiency virus. Ann. Intern. Med. 105:968 (1986).

    Google Scholar 

  19. Centers for Disease Control (CDC). Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Morbid. Mortal. Week. Rep. 37(suppl. no. 1S):3S–15S (1987).

    Google Scholar 

  20. H. Rübsamen-Waigmann, W. R. Willems, V. Bertram, and H. von Briesen. Reversal of HIV phenotype to fulminant replication on macrophages in perinatal transmission. Lancet 2:1155–1156 (1989).

    Google Scholar 

  21. H. Rübsamen-Waigmann, W. B. Becker, E. B. Helm, R. Brodt, H. Fischer, K. Henco, and H. D. Brede. Isolation of variants of lymphocytopathic retroviruses from the peripheral blood and cerebrospinal fluid of patients with ARC or AIDS. J. Med. Virol. 19:335–344 (1986).

    Google Scholar 

  22. J. Kreuter. Evaluation of nanoparticles as a drug delivery system I. J. Pharm. Acta Helv. 58:196–208 (1983).

    Google Scholar 

  23. J. J. Marty, R. C. Oppenheim, and P. P. Speiser. Nanoparticles: A new colloidal drug delivery system. Pharm. Acta Helv. 53:17–23 (1978).

    Google Scholar 

  24. K. Widder, G. Flouret, and A. Senyei. Magnetic microspheres: Synthesis of a novel parenteral drug carrier. J. Pharm. Sci. 68:79–82 (1979).

    Google Scholar 

  25. Y. Ikada and Y. Tabata. Phagocytosis of bioactive polymers. J. Bioact. Polym. 1:32–46 (1986).

    Google Scholar 

  26. R. Esser, H. von Briesen, M. Ceska, W. Glienke, S. Müller, A. Rehm, H. Rübsamen-Waigmann, and R. Andreesen. Secretory repertoire of HIV-infected human monocytes/macrophages. Pathobiology 59:219–222 (1990).

    Google Scholar 

  27. C. L'Herm, R. H. Müller, and P. Couvreur. Cytotoxicity of polyalkylcyanoacrylate particles in L929 fibroblast cultures—mechanism of the toxic effect. Abstracts DPhG Annual Meeting 1989, p. 682.

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Schäfer, V., von Briesen, H., Andreesen, R. et al. Phagocytosis of Nanoparticles by Human Immunodeficiency Virus (HlV)-Infected Macrophages: A Possibility for Antiviral Drug Targeting. Pharm Res 9, 541–546 (1992). https://doi.org/10.1023/A:1015852732512

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  • DOI: https://doi.org/10.1023/A:1015852732512

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