Development of Linker-Conjugated Nanosize Lipid Vesicles: A Strategy for Cell Selective Treatment in Breast Cancer
Development of Linker-Conjugated Nanosize Lipid Vesicles: A Strategy for Cell Selective Treatment in Breast Cancer
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DOI：
10.2174/1568009616666151106120606
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发表时间：
2016-01-01
影响因子：
3
通讯作者：
Satapathy, Bhabani Sankar
中科院分区：
文献类型：
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作者：
Dey, Niladri Shekhar;Mukherjee, Biswajit;Satapathy, Bhabani Sankar
在各种药物递送装置中，纳米脂质体是治疗癌症的新兴制剂。本文采用薄膜水合法制备了磷酸乙醇胺（PE）修饰的枸橼酸他莫昔芬（TC）纳米脂质体。进行了各种理化和生物制药表征研究，如药物-辅料相互作用、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、体外细胞毒性试验和体内药代动力学特征。负载TC的纳米脂质体（TNL 1）和PE缀合的负载TC的纳米脂质体（TNL-PE）分别显示3.23 +/- 0.26%和3.07 +/- 0.05%载药量值。纳米脂质体的平均直径（z-平均值）在100 nm内，对于TNL 1和TNL-PE，在30 h时具有负zeta电位和药物释放的累积百分比分别为75.77 +/- 12.21%和61.04 +/- 10.53%。在MCF-7乳腺癌细胞中观察到两种类型的纳米脂质体的主要摄取。TNL 1和TNL-PE分别将细胞活力从95.95 +/-0.37%降低至12.22 +/- 0.64%和从96.51 +/-0.24%降低至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AUC（0-无穷大）、AUMC（0-无穷大）、MRT和t（1/2）值分别增加22%、100%、2.66倍和60%。与游离药物相比，TNL-PE给药降低了肾清除率值（约38%）。TNL 1和TNL-PE以持续的方式释放药物。此外，当TNL-PE用PE（接头分子）的特异性抗体标记时，TNL-PE可用于主动靶向乳腺癌细胞。
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-infinity), AUMC(0-infinity), MRT, and t(1/2) 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.