Influence of surface-modifying surfactants on the pharmacokinetic behavior of 14C-poly (methylmethacrylate) nanoparticles in experimental tumor models.
OBJECTIVE
The aim of this study was to investigate the different pharmacokinetic behavior of surface-modified poly(methylmethacrylate) (PMMA) nanoparticles.


METHODS
The particles were 14C-labeled and coated with polysorbate 80, poloxamer 407, and poloxamine 908. Plain particles served as control particles. In vivo studies were performed in three tumor models differing in growth, localization, and origin. Particle suspensions were administered via the tail vein, and at given time animals were killed and organs were dissected for determination of PMMA concentration.


RESULTS
For the PMMA nanoparticles coated with poloxamer 407 or poloxamine 908, high and long-lasting concentrations were observed in the melanoma and at a lower level in the breast cancer model. In an intracerebrally growing glioma xenograft, the lowest concentrations that did not differ between the tumor-loaded and tumor-free hemispheres were measured. Organ distribution of the four investigated batches differed significantly. For instance, poloxamer 407- and poloxamine 908-coated particles circulated over a longer period of time in the blood, leading additionally to a higher tumor accumulation. In contrast, plain and polysorbate 80-coated particles accumulated mainly in the liver. The strong expression of vascular endothelial growth factor and Flk-1 in the melanoma correlated with high concentrations of PMMA in this tumor.


CONCLUSIONS
The degree of accumulation of PMMA nanoparticles in tumors depended on the particle surface properties and the specific growth differences of tumors.
Lode
J
J
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Fichtner
I
I
Kreuter
J
J
Berndt
A
A
Diederichs
J E
JE
Reszka
R
R
D000818:Animals; D019540:Area Under Curve; D001812:Blood-Brain Barrier; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008222:Lymphokines / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008863:Microspheres; D009368:Neoplasm Transplantation; D019904:Polymethyl Methacrylate / Q000737:chemistry* / Q000493:pharmacokinetics*; D013501:Surface-Active Agents / Q000737:chemistry*; D013535:Suspensions; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D013501:Surface-Active Agents; D013535:Suspensions; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019904:Polymethyl Methacrylate