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

• Published in: Pharmaceutical research 1999-10, Vol.16 (10), p.1564-1569
• Main Authors: Gulyaev, A E, Gelperina, S E, Skidan, I N, Antropov, A S, Kivman, G Y, Kreuter, J
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacokinetics; Area Under Curve; Blood-Brain Barrier; Brain - metabolism; Chromatography, High Pressure Liquid; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Excipients; Half-Life; Injections, Intravenous; Microspheres; Polysorbates; Rats; Rats, Wistar; Tissue Distribution
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1018983904537

To investigate the possibility of delivering of anticancer drugs into the brain using colloidal carriers (nanoparticles). Rats obtained 5 mg/kg of doxorubicin by i.v. injection in form of 4 preparations: 1. a simple solution in saline, 2. a simple solution in polysorbate 80 1% in saline, 3. bound to poly(butyl cyanoacrylate) nanoparticles, and 4. bound to poly(butyl cyanoacrylate) nanoparticles overcoated with 1% polysorbate 80 (Tween 80). After sacrifice of the animals after 10 min, 1, 2, 4, 6, and 8 hours, the doxorubicin concentrations in plasma, liver, spleen, lungs, kidneys, heart and brain were determined after extraction by HPLC. No significant difference in the body distribution was observed between the two solution formulations. The two nanoparticle formulations very significantly decreased the heart concentrations. High brain concentrations of doxorubicin (>6 microg/g) were achieved with the nanoparticles overcoated with polysorbate 80 between 2 and 4 hours. The brain concentrations observed with the other three preparations were always below the detection limit (< 0.1 microg/g). The present study demonstrates that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by binding to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated with the nonionic surfactant polysorbate 80. It is highly probable that coated particles reached the brain intact and released the drug after endocytosis by the brain blood vessel endothelial cells.