Journal of Drug Targeting, 01 January 2006, Vol.14(2), pp.97-105
It was recently shown that doxorubicin (DOX) bound to polysorbate-coated nanoparticles (NP) crossed the intact blood-brain barrier (BBB), and thus reached therapeutic concentrations in the brain. Here, we investigated the biodistribution in the brain and in the body of poly(butyl-2-cyano[3- 14 C]acrylate) NP ([ 14 C]-PBCA NP), polysorbate 80 (PS 80)-coated [ 14 C]-PBCA NP, DOX-loaded [ 14 C]-PBCA NP in glioblastoma 101/8-bearing rats after i.v. injection. The biodistribution profiles and brain concentrations of radiolabeled NP were determined by radioactivity counting after i.v. administration in rats. Changes in BBB permeability after tumour inoculation were assessed by i.v. injection of Evans Blue solution. The accumulation of NP in the tumour site and in the contralateral hemisphere in glioblastoma bearing-rats probably was augmented by the enhanced permeability and retention effect (EPR effect) that may have been becoming instrumental due to the impaired BBB on the NP delivery into the brain. The uptake of the NP by the organs of the reticuloendothelial system (RES) was reduced after PS 80-coating, but the addition of DOX increased again the concentration of NP in the RES.
Blood-Brain Barrier ; Glioblastoma ; Nanoparticles ; Doxorubicin ; Polysorbate 80 ; Pharmacy, Therapeutics, & Pharmacology
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