Tissue distribution of doxorubicin associated with polyisohexylcyanoacrylate nanoparticles

Abstract

The body distribution of i. v. doxorubicin depends mainly on the physicochemical characteristics of the molecule. However, entrapment of that cytostatic drug inside polyalkylcyanoacrylate nanoparticles has been shown to modify its distribution profoundly in the mouse. Polyisohexylcyanoacrylate nanoparticles loaded with [¹⁴C]-doxorubicin were studied in comparison with free drug, with emphasis on their distribution pattern in mouse tissue after i. v. administration. An autoradiographic study showed that most of the radioactivity was found in the reticuloendothelial system as soon as a few minutes after i. v. administration of the doxorubicin-loaded nanoparticles. Quantitative determinations by liquid scintillation counting in fresh tissue (spleen, heart, kidneys, liver, lungs, bone marrow) and blood samples confirmed these observations. When the drug was linked to nanoparticles, doxorubicin blood clearance was reduced during the first few minutes after administration, whereas heart and kidney concentrations were substantially decreased. Assays of doxorubicin and doxorubicinol by a specific HPLC analytical method gave results very similar to those obtained by scintillation counting.