Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles

Purpose. To investigate the possibility of delivering of anticancer drugs i nto the brain using colloidal carriers (nanoparticles). Methods. Rats obtained 5 mg/kg of doxorubicin by i. v. injection in form of 4 preparations : i. a simple solution in saline, 2. a simple solution in p olysorbate 80 1% in saline, 3.bound to poly(butyl cyanoacrylate) nanopartic les, and 4. bound to poly(butyl cyanoacrylate) nanoparticles overcoated wit h 1% polysorbate 80 (Tween(R) 80). After sacrifice of the animals after 10 min, 1, 2, 4, 6, and 8 hours, the doxorubicin concentrations in plasma, liv er, spleen, lungs, kidneys, heart and brain were determined after extractio n by HPLC. Results. No significant difference in the body distribution was observed be tween the two solution formulations. The two nanoparticle formulations very significantly decreased the heart concentrations. High brain concentration s of doxorubicin (>6 mu g/g) were achieved with the nanoparticles overcoate d with polysorbate 80 between 2 and 4 hours. The brain concentrations obser ved with the other three preparations were always below the detection Limit (< 0.1 mu g/g). Conclusions. The present study demonstrates that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by bind ing to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated wi th the nonionic surfactant polysorbate 80. It is highly probable that coate d particles reached the brain intact and released the drug after endocytosi s by the brain blood vessel endothelial cells.