Influence of surface-modifying surfactants on the pharmacokinetic behaviorof C-14-poly (methylmethacrylate) nanoparticles in experimental tumor models

Purpose. The aim of this study was to investigate the different pharmacokin etic behavior of surface-modified poly(methylmethacrylate) (PMMA) nanoparti cles. Methods. The particles were C-14-labeled and coated with polysorbate 80, po loxamer 407, and poloxamine 908. Plain particles served as control particle s. 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 an d at a lower level in the breast cancer model. In an intracerebrally g-rowi ng glioma xenograft, the lowest concentrations that did not differ between the tumor-loaded and tumor-free hemispheres were measured. Organ distributi on of the four investigated batches differed significantly. For instance, p oloxamer 407- and poloxamine 908-coated particles circulated over a longer period of time in the blood, leading additionally to a higher tumor accumul ation. In contrast, plain and polysorbate 80-coated particles accumulated m ainly in the liver, The strong expression of vascular endothelial growth fa ctor and Flk-1 in the melanoma correlated with high concentrations of PMMA in this tumor. Conclusion. The degree of accumulation of PMMA nanoparticles in tumors depe nded on the particle surface properties and the specific growth differences of tumors.