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.
Highlights
The synthesis and structures of furano-allocolchicinoid analogues are shown on Schemes 1 and 2
All conjugates were obtained using Steglich conditions; rhodamine derivative was synthesized according to the published procedure from commercial rhodamine
Our results demonstrated that an increase in the size of the preparation results in the increase in the biodistribution
Summary
Natural alkaloid colchicine (1) (Figure 1) is a mitotic poison that binds to intracellular protein tubulin and prevents mitotic spindle formation. This leads to a block in cell proliferation and reduced cell motility [1,2]. Administrated colchicine has an elimination half-life of 20–40 h [3]. It binds to neutrophils and serum albumin and may cause the body to produce fewer blood cells of different types [4]. Numerous attempts have been made to modify the molecule in order to reduce its inherent toxic side effects [6]
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