Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700032, India.
Curr Cancer Drug Targets. 2016;16(4):357-72. doi: 10.2174/1568009616666151106120606.
Among the various drug delivery devices, nanoliposome is an emerging formulation in the treatment of cancer. Here we have developed tamoxifen citrate (TC) loaded nanoliposome conjugated with phosphoethanolamine (PE) by thin film hydration method. Various physicochemical and biopharmaceutical characterization studies such as drug-excipients interaction, surface morphology, energy dispersive X-ray analysis, zeta potential, in vitro drug release, cellular uptake, in vitro cytotoxicity assay and in vivo pharmacokinetic profiles were conducted. TC-loaded nanoliposome (TNL1) and PE-conjugated TC-loaded nanoliposome (TNL-PE) showed 3.23±0.26% and 3.07±0.05% drug loading values, respectively. Average diameters (z-average) of the nanoliposomes were within 100 nm, with negative zeta potentials and cumulative percentages of drug release were 75.77±12.21% and 61.04±10.53% at 30 h for TNL1 and TNL-PE respectively. Predominant uptake of both the types of nanoliposomes was visualized in MCF-7 breast cancer cells. TNL1 and TNL-PE decreased the cell viability from 95.95±0.37 to 12.22±0.64% and from 96.51±0.24 to 13.49±0.08% respectively. In vivo pharmacokinetic study showed that AUC 0-∞, AUMC0-∞, MRT, and t1/2 value of TNL-PE increased (22%, 100%, 2.66 fold and 60% respectively) as compared to the free drug. Administration of TNL-PE decreased the renal clearance value (about 38%) as compared to the free drug. TNL1 and TNL-PE released the drug in a sustained manner. Further, TNL-PE may be used for active targeting for breast cancer cells when it is tagged with specific antibodies to PE, a linker molecule.
在各种药物输送装置中，纳米脂质体是癌症治疗中一种新兴的制剂。在这里，我们通过薄膜水化法开发了载有柠檬酸他莫昔芬（TC）的纳米脂质体与磷乙醇胺（PE）的轭合物。进行了各种物理化学和生物制药特性研究，例如药物-赋形剂相互作用、表面形态、能量色散 X 射线分析、Zeta 电位、体外药物释放、细胞摄取、体外细胞毒性测定和体内药代动力学特征。TC 负载的纳米脂质体（TNL1）和 PE 共轭 TC 负载的纳米脂质体（TNL-PE）分别显示 3.23±0.26%和 3.07±0.05%的药物负载值。纳米脂质体的平均直径（z 平均）在 100nm 以内，具有负 Zeta 电位，TNL1 和 TNL-PE 的累积药物释放百分比分别为 30h 时的 75.77±12.21%和 61.04±10.53%。两种类型的纳米脂质体在 MCF-7 乳腺癌细胞中的摄取均占主导地位。TNL1 和 TNL-PE 使细胞活力从 95.95±0.37%分别降低至 12.22±0.64%和 96.51±0.24%至 13.49±0.08%。体内药代动力学研究表明，与游离药物相比，TNL-PE 的 AUC0-∞、AUMC0-∞、MRT 和 t1/2 值分别增加（22%、100%、2.66 倍和 60%）。与游离药物相比，TNL-PE 降低了肾清除率值（约 38%）。TNL1 和 TNL-PE 以持续的方式释放药物。此外，当与 PE（一种连接分子）的特定抗体缀合时，TNL-PE 可用于针对乳腺癌细胞的主动靶向。
