Indian Journal of Nuclear Medicine

Delivery of drugs to the target sites by the use of carrier systems has recently been the major area of drug delivery research. Incorporation of drugs into delivery carriers prevents drugs from degradation, targets the drug to the site of action and reduces toxicity or side effects by modifying their in vivo distribution. Delivery of anticancer agents using carrier systems with an objective of enhancing their tumor concentrations has been widely attempted. Over the years, surfactants have been of pharmaceutical interest either as drug carriers or, more recently, as targeting systems. The very small size of nanoparticles (< 100 nm) prevents uptake by the reticuloendothelial system and facilitates their extra vasation at leaky sites of capillaries, leading to passive accumulation in tumor tissues and penetration into cells.

Etoposide (ET) is an anticancer agent used in the treatment of a variety of malignancies and has been demonstrated to be effective in the treatment of small cell lung carcinoma, brain stem gliomas, malignant lymphoma and ovarian cancer. The present study describes our attempt to enhance the delivery of etoposide to Ehrlich Ascites solid tumor in mice by incorporating etoposide into nanoparticles. Etoposide (ET) and etoposide loaded nanoparticles were radiolabeled with Tc-99m by the reduction method using stannous chloride. Labeling parameters were optimized to obtain high labeling efficiency. The diethylenetriaminepentaacetic acid and cysteine challenge tests showed less than 2% transchelation of Tc-99m-ET at 24 hr indicating their high in vitro stability. The complexes also exhibited serum stability assessed by ascending instant thin layer chromatography. At 30 minutes post i.v. administration, greater concentrations of etoposide were found in liver. The overall uptake of etoposide loaded polylactic glycolic acid (PLGA), polycynoacrlate (PCL) and empty nanoparticle formulations by liver and spleen were significantly lower than that of free etoposide. The spleen uptake of all nanoparticles was low initially but increased with time. Nanoparticles of PLGA and PCL were taken up by lungs in higher concentration as compared to free etoposide. This is useful finding as the main use of etoposide is in chemotherapy of lung cancer. Elimination of nanoparticles through kidney was less when compared to free drug. Nanoparticles were taken up significantly by bone marrow, which was also be visualized in gamma scintigraphy. Enhanced accumulation of radiolabelled nanoparticles in tumor, confirmed by gamma imaging studies, proves the potential use of the developed system in chemotherapy.