Nanoemulsion enhances α-tocopherol succinate bioavailability in rats
Nanoemulsion enhances α-tocopherol succinate bioavailability in rats
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DOI：
10.1016/j.ijpharm.2016.10.026
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发表时间：
2016-12-30
影响因子：
5.8
通讯作者：
Tang, Jingling
中科院分区：
文献类型：
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作者：
Gao, Yanan;Qi, Xuejing;Tang, Jingling
维生素E类似物α-生育酚琥珀酸酯（α-TOS）具有广泛的抗肿瘤作用。α-TOS可通过靶向线粒体诱导肿瘤细胞凋亡并抑制肿瘤生长。α-TOS的低生物利用度是制剂开发中遇到的主要问题。本研究将α-TOS纳米乳（alpha-TOS-NE）作为α-TOS的一种新型给药系统，以提高其生物利用度。对人乳腺癌细胞系MCF-7和人口腔上皮癌细胞系KB进行基于MTT的细胞毒性测定和线粒体膜电位（DY）以评价α-TOS-NE的体外抗癌功效。与游离alpha-TOS相比，alpha-TOS-NE表现出更强的细胞毒性并降低Delta Psi。绘制了静脉注射α-TOS-NE组、腹腔注射α-TOS-NE组和腹腔注射游离α-TOS组（7%DMSO/93%PEG）的药代动力学曲线。首先，纳米乳剂（NE）使α-TOS的静脉注射成为可能，使其成为一种静脉制剂。第二，与I. P.游离α-TOS组相比，I. P. α-TOS-NE组具有更高的生物利用度。因此，NE改善了α-TOS的强抗癌功效，同时增加了其在大鼠中的体内生物利用度。总之，我们的实验室制造的NE是一个安全的药物递送系统的临床试验，并可能是一个有前途的制剂，通过静脉注射给药的α-TOS。(C)© 2016 Elsevier B. V.版权所有。
The vitamin E analogue, alpha-tocopherol succinate (alpha-TOS), has a broad anti-tumor effect. alpha-TOS can induce cancer cells apoptosis and suppress tumor growth by targeting mitochondria. Low bioavailability of alpha-TOS is the major problem encountered with formulation development. In our study, alpha-TOS nanoemulsion (alpha-TOS-NE) was demonstrated as a new drug delivery system of alpha-TOS to increase the bioavailability. MTT-based cytotoxicity assay and mitochondrial membrane potential (DY) were performed on human breast cancer cell lines MCF-7 and human oral epithelial cancer cell lines KB to evaluate in vitro anticancer efficacy of alpha-TOS-NE. In comparison with free alpha-TOS, alpha-TOS-NE exhibited a stronger cytotoxicity and decreased Delta Psi. Pharmacokinetic profiles of I.V. alpha-TOS-NE group, I.P. alpha-TOS-NE group, and I.P. free alpha-TOS group (7% DMSO/93% PEG) were drawn. First of all, nanoemultion (NE) enables the I.V. injection of alpha-TOS, make it possible to be an I.V. preparation. Second, compare to the I.P. free alpha-TOS group, I.P. alpha-TOS-NE group had a higher bioavailability. Thus, NE improved the strong anti-cancer efficacy of alpha-TOS while increasing its in vivo bioavailability in rats. In conclusion, our laboratory-made NE was a safe drug delivery system for clinical trials and could be a promising formulation for alpha-TOS by I.V administration. (C) 2016 Elsevier B.V. All rights reserved.