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Abstract
The aim of this study was to compare the biodistribution in mice of functionalized rhodamine B (Rh) labeled colchicine derivative furano-allocolchicinoid (AC, 6) either conjugated to 40 kDa chitosan (AC-Chi, 8) or encapsulated into chitosan nanoparticles (AC-NPs). AC-NPs were formed by ionotropic gelation and were 400–450 nm in diameter as estimated in mice by dynamic light scattering and confocal microscopy. AC-Chi and AC-NPs preserved the specific colchicine activity in vitro. AC preparations were once IV injected into C75BL/6 mice; muscles, spleen, kidney, liver, lungs, blood cells and serum were collected at 30 min, 2, 5, 10, and 20 h post injection. To analyze the distribution of the furano-allocolchicinoid preparations in body liquids and tissues, Rh was measured directly in sera or extracted by acidic ethanol from tissue homogenates. Preliminary Rh extraction rate was estimated in vitro in tissue homogenates and was around 25–30% from total quantity added. After in vivo injection, AC-NPs were accumulated more in liver and spleen, while less in kidney and lungs in comparison with free AC and AC-Chi. Therefore, incorporation of colchicine derivatives as well as other hydrophobic substances into nano/micro sized carriers may help redistribute the drug to different organs and, possibly, improve antitumor accumulation.
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