Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, 470003 Sagar, MP, India.
Cancer Pharmacology Division, Indian Institute of Integrative Medicine, 180001 Jammu, India.
Colloids Surf B Biointerfaces. 2015 Feb 1;126:414-25. doi: 10.1016/j.colsurfb.2014.12.045. Epub 2015 Jan 8.
The object of the present study was to investigate the glioma targeting propensity of folic acid (F) decorated polymer-lipid hybrid nanoparticles (PLNs) encapsulating cyclo-[Arg-Gly-Asp-D-Phe-Lys] (cRGDfK) modified paclitaxel (PtxR-FPLNs). The prepared PLNs were supposed to bypass the blood-brain barrier (BBB) efficiently and subsequently target integrin rich glioma cells. The developed formulations were characterized for size, shape, drug entrapment efficiency, and in vitro release profile. PtxR-FPLNs demonstrated highest in vitro inhibitory effect, cell apoptosis and cell uptake. Pharmacokinetics and biodistribution studies showed efficacy of PtxR-FPLNs in vivo. In vivo anti-tumor studies clearly revealed that the median survival time for Balb/C mice treated with PtxR-FPLNs (42 days) was extended significantly as compared to PtxR-PLNs (35 days), free PtxR (18 days), Ptx-FPLNs (38 days), Ptx-PLNs (30 days), free Ptx (14 days) and control group (12 days). From the results it can be concluded that the developed dual targeted nanoformulation was able to efficiently cross the BBB and significantly deliver higher amounts of drug to brain tumor for better therapeutic outcome.
本研究的目的是研究叶酸（F）修饰的聚合物-脂质杂化纳米粒（PLNs）包载环-[精氨酸-甘氨酸-天冬氨酸-D-苯丙氨酸-赖氨酸]（cRGDfK）修饰紫杉醇（PtxR-FPLNs）对神经胶质瘤的靶向性。所制备的 PLNs 有望高效地绕过血脑屏障（BBB），随后靶向整合素丰富的神经胶质瘤细胞。对开发的制剂进行了大小、形状、药物包封效率和体外释放特性的表征。PtxR-FPLNs 表现出最高的体外抑制效果、细胞凋亡和细胞摄取。药代动力学和生物分布研究表明 PtxR-FPLNs 在体内具有疗效。体内抗肿瘤研究清楚地表明，用 PtxR-FPLNs（42 天）治疗的 Balb/C 小鼠的中位存活时间明显延长，与 PtxR-PLNs（35 天）、游离 PtxR（18 天）、Ptx-FPLNs（38 天）、Ptx-PLNs（30 天）、游离 Ptx（14 天）和对照组（12 天）相比。结果表明，所开发的双重靶向纳米制剂能够有效地穿过血脑屏障，并将更多的药物递送到脑肿瘤中，以获得更好的治疗效果。
