Reddy Lakkireddy Harivardhan, Sharma Rakesh Kumar, Murthy Rayasa Ramachandra
Drug Delivery Research Laboratory, Center of Relevance and Excellence in NDDS, Pharmacy Department, G.H. Patel Building, Donor's Plaza, Fatehgunj Baroda-390002, Gujarat, India.
Acta Pharm. 2006 Jun;56(2):143-55.
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.
该研究评估了通过聚山梨酯20胶束递送时，增强肿瘤对依托泊苷（拓扑异构酶II抑制剂）摄取的可能性。通过使用杜诺伊环张力计测定临界胶束浓度（CMC）以及使用动态光散射测量尺寸来确定胶束的形成。添加5%乙醇降低了聚山梨酯20的CMC（从5.0×10⁻⁵降至4.54×10⁻⁵mol L⁻¹）。依托泊苷（ET）和负载依托泊苷的聚山梨酯20胶束（EPM）通过使用氯化亚锡的还原法用⁹⁹ᵐTc进行放射性标记。优化标记参数以获得高标记效率。二乙三胺五乙酸和半胱氨酸激发试验表明，⁹⁹ᵐTc - ET和⁹⁹ᵐTc - EPM复合物的转螯合作用非常低，表明它们在体外具有稳定性。通过上行薄层色谱法评估，这些复合物也表现出血清稳定性。皮下注射EPM导致肿瘤摄取显著更高（注射后6小时比ET高100倍）（p < 0.001）且肿瘤滞留时间延长。γ成像研究也证实了肿瘤摄取。与ET相比，EPM在注射后24小时表现出相对较高的脑浓度（高7倍），表明EPM在治疗脑恶性肿瘤方面具有潜在用途。
