Investigations on the interactions between curcumin loaded vitamin E TPGS coated nanodiamond and Caco-2 cell monolayer
Investigations on the interactions between curcumin loaded vitamin E TPGS coated nanodiamond and Caco-2 cell monolayer
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姜黄素负载维生素 E TPGS 包覆纳米金刚石与 Caco-2 细胞单层之间相互作用的研究
DOI：
10.1016/j.ijpharm.2018.09.030
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发表时间：
2018
影响因子：
5.8
通讯作者：
Pan Hao
中科院分区：
文献类型：
--
作者：
Liu D;an;Cheng Bingchao;Li Dongyang;Li Jinyu;Wu Qingyin;Pan Hao
采用体外Caco-2细胞单层模型研究姜黄素负载D-α-生育酚聚乙二醇1000琥珀酸酯涂层纳米金刚石系统（NDs/CUR/TPGS复合物）改善转运的潜在机制。核壳结构的NDs/CUR/TPGS纳米复合物的粒径为196.32 ± 5.76 nm，负载效率为81.59 ± 3.42%。细胞毒性实验结果表明，空白NDs孵育72 h后对Caco-2细胞无明显毒性作用。结果表明，所有系列CUR负载制剂的细胞存活率顺序为CUR悬浮液> ND/CUR > ND/CUR/TPGS。共聚焦激光荧光显微镜（CLSM）和流式细胞仪（FACS）研究证实，TPGS修饰可以有效地增强细胞对NDs的摄取。NDs/CUR和TPGS包被蛋白的转运机制主要是通过能量依赖的、网格蛋白介导的和小窝蛋白介导的内吞作用，NDs/CUR的内吞作用也是通过巨胞饮作用。此外，NDs/CUR和NDs/CUR/TPGS的Papp值（AP-BL）分别是CUR悬浮液的2.09倍和3.86倍。结果表明，NDs/CUR/TPGS纳米复合物能显著增强CUR的药理活性和肠通透性。因此，NDs可能是一个有前途的口服药物传递平台，用于改善肠道渗透性和口服生物利用度的难溶性药物。
This study aimed at investigating the potential mechanism of improved transportation of the curcumin loaded D-α-tocopherol polyethylene glycol 1000 succinate coated nanodiamonds system (NDs/CUR/TPGS complexes) using an in vitro Caco-2 cell monolayer model. The core–shell structured NDs/CUR/TPGS nanocomplexes were 196.32 ± 5.76 nm in size, with a high loading efficiency of 81.59 ± 3.42%. Cytotoxicity results suggested that the blank NDs did not induce any serious toxicity on Caco-2 cells even after incubated for 72 h. The cell viability for all the series of CUR loaded preparations was found to follow the sequence of CUR suspension > NDs/CUR > NDs/CUR/TPGS. Confocal laser fluorescence microscopy (CLSM) and flow cytometry system (FACS) studies confirmed that the cellular uptake of NDs could be efficiently enhanced by TPGS decoration. The transport mechanism of NDs/CUR and TPGS coated ones was mainly through an energy dependent, clathrin-mediated and caveolin-mediated endocytosis, and the endocytosis of NDs/CUR was also via macropinocytosis. Furthermore, the Pappvalue (AP-BL) of NDs/CUR and NDs/CUR/TPGS was 2.09- and 3.86-fold higher than that of the CUR suspension. All the results demonstrated that the pharmacological activates and intestinal permeability of CUR across Caco-2 cell monolayer was greatly enhanced by NDs/CUR/TPGS nanocomplexes. Thus NDs could be a promising oral drug delivery platform for improving the intestinal permeability and oral bioavailability of poorly soluble drugs.