Yao Hua, Ma Jinqi
Department of Gynecology and Obstetrics, The second People's Hospital of Nantong, Nantong, Jiangsu 226002, China.
Department of Obstetrics, Wuxi People's Hospital, Wuxi, Jiangsu 214023, China.
Acta Biochim Pol. 2018;65(2):219-225. doi: 10.18388/abp.2017_2331. Epub 2018 Jun 18.
The present paper investigates the enhancement of the therapeutic effect of Paclitaxel (a potent anticancer drug) by increasing its cellular uptake in the cancerous cells with subsequent reduction in its cytotoxic effects. To fulfill these goals the Paclitaxel (PTX)-Biotinylated PAMAM dendrimer complexes were prepared using biotinylation method. The primary parameter of Biotinylated PAMAM with a terminal HN group - the degree of biotinylation - was evaluated using HABA assay. The basic integrity of the complex was studied using DSC. The Drug Loading (DL) and Drug Release (DR) parameters of Biotinylated PAMAM dendrimer-PTX complexes were also examined. Cellular uptake study was performed in OVCAR-3 and HEK293T cells using fluorescence technique. The statistical analysis was also performed to support the experimental data. The results obtained from HABA assay showed the complete biotinylation of PAMAM dendrimer. DSC study confirmed the integrity of the complex as compared with pure drug, biotinylated complex and their physical mixture. Batch 9 showed the highest DL (12.09%) and DR (70%) for 72 h as compared to different concentrations of drug and biotinylated complex. The OVCAR-3 (cancerous) cells were characterized by more intensive cellular uptake of the complexes than HEK293T (normal) cells. The obtained experimental results were supported by the statistical data. The results obtained from both experimental and statistical evaluation confirmed that the biotinylated PAMAM NH dendrimer-PTX complex not only displays increased cellular uptake but has also enhanced release up to 72 h with the reduction in cytotoxicity.
本文研究了通过增加紫杉醇（一种有效的抗癌药物）在癌细胞中的细胞摄取量，随后降低其细胞毒性作用来增强其治疗效果。为实现这些目标，采用生物素化方法制备了紫杉醇（PTX）-生物素化聚酰胺-胺（PAMAM）树枝状大分子复合物。使用HABA分析法评估了带有末端HN基团的生物素化PAMAM的主要参数——生物素化程度。使用差示扫描量热法（DSC）研究了复合物的基本完整性。还检测了生物素化PAMAM树枝状大分子-PTX复合物的载药量（DL）和药物释放（DR）参数。使用荧光技术在OVCAR-3和HEK293T细胞中进行了细胞摄取研究。还进行了统计分析以支持实验数据。HABA分析获得的结果表明PAMAM树枝状大分子已完全生物素化。与纯药物、生物素化复合物及其物理混合物相比，DSC研究证实了复合物的完整性。与不同浓度的药物和生物素化复合物相比，第9批在72小时内显示出最高的载药量（12.09%）和药物释放率（70%）。OVCAR-3（癌）细胞的特征是比HEK293T（正常）细胞对复合物的细胞摄取更强烈。获得的实验结果得到了统计数据的支持。从实验和统计评估中获得的结果证实，生物素化的PAMAM NH树枝状大分子-PTX复合物不仅显示出细胞摄取增加，而且在72小时内药物释放增强，同时细胞毒性降低。
