Development of a safety and efficacy nanoemulsion delivery system encapsulated gambogic acid for acute myeloid leukemia in vitro and in vivo
Development of a safety and efficacy nanoemulsion delivery system encapsulated gambogic acid for acute myeloid leukemia in vitro and in vivo
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开发安全有效的藤黄酸纳米乳递送系统，用于体外和体内治疗急性髓系白血病
DOI：
10.1016/j.ejps.2018.10.001
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发表时间：
2018-12-01
影响因子：
4.6
通讯作者：
Sun, Hongwu
中科院分区：
文献类型：
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作者：
Feng, Ziqi;Wang, Zelin;Sun, Hongwu
本研究旨在提高藤黄酸的溶解度，减少其毒副作用，提高其体内外抗急性髓系白血病的疗效。通过拟三元相图制备了含吐温-80、乙二醇、角鲨烯和藤黄酸的水包油型纳米乳液（平均粒径17.20 ± 0.11 nm，zeta电位4.17 ± 0.82 mV），溶解度提高了4000倍。结果表明，该纳米乳成功地包裹了藤黄酸，在pH = 2.0、5.8和7.4的磷酸盐缓冲液中稳定，并显示出明显的缓释效果。对毒性标准细胞株（L929）作用24 h和48 h后，纳米乳的半数抑制浓度（IC 50）（480.7 μ g/mL和408 μ g/mL）分别是水溶液（287 μ g/mL和206 μ g/mL）的1.67倍和1.98倍。重要的是，急性注射毒性表明该纳米乳的半致死量（LD 50）（23.25 mg/kg，95%LD 50，21.7-25.16 mg/kg）是其水溶液（18.59 mg/kg，95%LD 50，16.84-20.53 mg/kg）的1.26倍。与混悬液相比，纳米乳的生物利用度为318.2%。此外，该纳米乳通过改善存活时间和百分比（MV 4 -11移植小鼠）以及降低急性髓性白血病如Jurket、HL-60和MV 4 -11细胞中的半数抑制浓度值，在体外和体内对急性髓性白血病具有更好的功效。本研究提示该纳米乳可能成为一种有前途的治疗急性髓系白血病的药物。
This study aimed to improve the solubility, reduce the side effects and enhance the efficacy of gambogic acid against acute myeloid leukemia in vitro and in vivo. This oil-in-water nanoemulsion (average size 17.20 +/- 0.11 nm, zeta potential 4.17 +/- 0.82 mV) containing Tween-80, glycol, squalene and gambogic acid with improving 4000 times solubility was prepared by pseudoternary phase diagrams. We found that this nanoemulsion successfully encapsulated gambogic acid; it was stable and showed an obvious delayed release effect for the drug in three different phosphate-buffered saline (pH = 2.0, 5.8 and 7.4). The half inhibiting concentration (IC50) of this nanoemulsion (480.7 mu g/mL and 408 mu g/mL) were 1.67 times and 1.98 times higher than those of its water solution (287 mu g/mL and 206 mu g/mL) after acing on the toxicity standard cell line (L929 line) for 24 h and 48 h, respectively. Importantly, acute injection toxicity indicated that the half lethal dose (LD50) of this nanoemulsion (23.25 mg/kg, 95% LD50, 21.7-25.16 mg/kg) was 1.26 times higher than that of its water solution (18.59 mg/kg, 95% LD50, 16.84-20.53 mg/kg). Compared with its suspension, the bioavailability of this nanoemulsion was 318.2%. Furthermore, this nanoemulsion had a better efficacy against the acute myeloid leukemia in vitro and in vivo by improving the time and percent of survival (MV4-11 engrafts mice) and reducing half inhibiting concentration values in acute myeloid leukemia such as Jurket, HL-60 and MV4-11 cells. Our studies suggested that this nanoemulsion may be a promising therapeutic medicine for acute myeloid leukemia.