Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, School of Engineering & Technology, Dr. H. S. Gour University, Sagar, Madhya Pradesh, India.
J Drug Target. 2012 Dec;20(10):841-9. doi: 10.3109/1061186X.2012.719231. Epub 2012 Sep 20.
Brain tumor is insidious complication which is difficult to treat because of the poor uptake of many potentially useful antitumor drugs through the blood-brain barrier (BBB). Present study was aimed for developing and exploring the use of thiamine conjugated poly(propylene imine) (PPI) dendrimers for increased delivery of paclitaxel (PTX) across the BBB. PTX loaded thiamine conjugated PPI dendrimers (PTX-Tm-PPI) shown increased drug loading and reduced hemolytic toxicity with suitability for prolonged delivery of PTX during in vitro release. Ex vivo cytotoxicity studies of free PTX, PTX-PPI and PTX-Tm-PPI dendrimers over IMR-32 human neuroblastoma cell line revealed higher potential of PTX-Tm-PPI nanoconjugate to retard tumor cell viability as compared to plain PTX or PTX-PPI. In vivo pharmacokinetics studies revealed significant (p < 0.05) slow clearance of PTX from the body via Tm-PPI nanoconjugate. Biodistribution studies confirmed about the targeting efficiency and higher biodistribution of Tm-PPI conjugates into the brain. The results concluded that the developed nanoconjugate has potential to deliver significantly higher amount of drug to brain tumor for improved therapeutic outcome.
脑肿瘤是一种隐匿性并发症，由于许多潜在有用的抗肿瘤药物通过血脑屏障（BBB）的摄取能力较差，因此难以治疗。本研究旨在开发和探索使用硫胺素共轭聚（丙稀亚胺）（PPI）树枝状聚合物来增加紫杉醇（PTX）通过血脑屏障的传递。负载 PTX 的硫胺素共轭 PPI 树枝状聚合物（PTX-Tm-PPI）显示出增加的药物载量和降低的溶血毒性，适合在体外释放期间延长 PTX 的输送。游离 PTX、PTX-PPI 和 PTX-Tm-PPI 树枝状聚合物对 IMR-32 人神经母细胞瘤细胞系的体外细胞毒性研究表明，与普通 PTX 或 PTX-PPI 相比，PTX-Tm-PPI 纳米复合物具有更高的潜力来延缓肿瘤细胞活力。体内药代动力学研究表明，通过 Tm-PPI 纳米复合物从体内清除 PTX 的速度明显减慢（p < 0.05）。生物分布研究证实了 Tm-PPI 缀合物对大脑的靶向效率和更高的生物分布。研究结果表明，所开发的纳米复合物具有向脑肿瘤递送显著增加的药物量的潜力，从而改善治疗效果。
