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  • 1
    ISSN: 1573-904X
    Keywords: nanoparticles ; body distribution ; plasma proteins ; complement ; reticulo-endothelial system ; opsonization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The organ distribution of radiolabeled poly (methyl methacrylate) (PMMA) nanoparticles coated with plasma proteins and serum complement in rats was studied in order to determine the effect of serum complement on the particle phagocytosis by the organs of the reticulo-endothelial system (RES). Methods. PMMA-nanoparticles were coated overnight with plasma proteins or serum complement, and injected into Wistar rats. The body distribution of nanoparticles was measured by means of scintillation counting of organ samples. In addition, proteins adsorbed to the particle surface were inactivated by heat treatment prior to injection, and the particles's distribution was measured as described above. Results. Whereas uncoated nanoparticles (control group) were mainly taken up by the Kupffer cells in the liver, incubation of the particles in plasma for 12 h followed by heat inactivation reduced the particle concentrations in the liver to merely 22% after 30 min. After 120 min, liver concentrations were still lower than the control group, and almost 30% of the administered dose of the heat-inactivated particle group was present in non-RES organs and tissues. Particles with non-inactivated complement were accumulated in the lung at concentrations of 29% after 30 min, which increased to 71% after 120 min, whereas those coated with inactivated complement reached lung concentrations above 70% already after 30 min. Conclusions. Particles coated with plasma components are able to avoid uptake by the RES, especially after heat inactivation of the plasma components adsorbed. Adsorption and heat inactivation of complement proteins alone, however, does not have the same result as coating with plasma proteins followed by heat inactivation. Therefore, it is concluded that plasma components other than complement proteins take part in the process of RES activation and phagocytosis of injected nanoparticles.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: nanoparticles ; human immunodeficiency virus (HIV) ; macrophage ; drug targeting ; phagocytosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: 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.
    Type of Medium: Electronic Resource
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