Interaction of serum components with poly(methylmethacrylate) nanoparticles and the resulting body distribution after intravenous injection in rats.
Radiolabelled poly(methylmethacrylate) (PMMA) nanoparticles were coated with rat serum albumin (RSA), serum and inactivated serum, to examine the influence of these blood components on the body distribution of a model colloidal drug carrier. The particles were incubated overnight at 37 degrees C either in a 1% solution of RSA in phosphate buffered saline (PBS) or in serum obtained from the rats. A suspension of nanoparticles in PBS was used as a control. Serum complement inactivation was achieved by storage at 56 degrees C for 30 min. The suspensions were then injected intravenously via the tail vein of Wistar rats. The animals were sacrificed at five different time points (30 min, 2 h, 6 h, 24 h, and 7 d after injection) and two samples of each organ and two blood samples were weighed into scintillation vials. The radioactivity of each sample was then measured in a Beckman scintillation counter. Coating with RSA led to no significant change in the body distribution of the particles, whereas incubation in serum, especially with complement inactivation prior to injection, very significantly reduced the uptake of particles into the organs of the reticuloendothelial system (RES), e.g., liver, spleen, and bone marrow. At the same time, much higher concentrations of nanoparticles were observed in the serum and in non-RES organs and peripheral tissues (kidneys, muscles, and intestine). This effect was most pronounced after 30 min, but was still observable after 7 d.
Borchard
G
G
Institut für Pharmazeutische Technologie, J. W. Goethe Universität, Frankfurt a.M., Germany.
Kreuter
J
J
D000818:Animals; D003102:Colloids; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D004337:Drug Carriers; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D008768:Methylmethacrylates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008863:Microspheres; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D003102:Colloids; D003169:Complement Inactivator Proteins; D004337:Drug Carriers; D008768:Methylmethacrylates