The role of serum complement on the organ distribution of intravenously administered poly (methyl methacrylate) nanoparticles: effects of pre-coating with plasma and with serum complement.
OBJECTIVE
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 particle'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.
Borchard
G
G
Department of Biopharmacy and Pharmaceutical Technology, University of the Saarland, Saarbrücken, Germany.
Kreuter
J
J
D000818:Animals; D003165:Complement System Proteins / Q000737:chemistry*; D004337:Drug Carriers; D005260:Female; D007275:Injections, Intravenous; D007728:Kupffer Cells / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D012157:Mononuclear Phagocyte System / Q000187:drug effects*; D010587:Phagocytosis; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013696:Temperature
D004337:Drug Carriers; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D003165:Complement System Proteins