Acta Pharm. 56 (2006) 143-155[ Full paper in PDF ]
The study evaluates the possibility of enhancing uptake of etoposide (topoisomerase II inhibitor) by tumor when delivered through polysorbate 20 micelles. The micelle formation was ascertained by determining the critical micellar concentration (CMC) with a du Nouy ring tensiometer and by size measurement using dynamic light scattering. Addition of 5% ethanol decreased the CMC of polysorbate 20 (from 5.0 x 10-5 to 4.54 x 10-5 mol L-1). Etoposide (ET) and etoposide loaded Polysorbate 20 micelles (EPM) were radiolabeled with 99mTc by the reduction method using stannous chloride. Labeling parameters were optimized to obtain high labeling efficiency. The diethylenetriaminepentaacetic acid and cysteine challenge tests showed very low transchelation of 99mTc-ET and 99mTc-EPM complexes indicating their in vitro stability. The complexes also exhibited serum stability assessed by ascending thin layer chromatography. Subcutaneous injection of EPM resulted in significantly higher tumor uptake (~ 100 folds compared to ET 6 h post injection) (p < 0.001) and prolonged tumor retention. Tumor uptake was also confirmed by gamma imaging studies. EPM exhibited relatively high brain concentrations (~7 fold 24 h post injection) compared to ET, suggesting the potential use of EPM in the treatment of brain malignancies.
Keywords: etoposide, polysorbate micelles, drug delivery, radiolabeling, biodistribution, tumor transport