National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Medical Laboratory, Third Military Medical University of Chinese PLA, Chongqing 400038, PR China.
National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Medical Laboratory, Third Military Medical University of Chinese PLA, Chongqing 400038, PR China.
Eur J Pharm Sci. 2018 Dec 1;125:172-180. doi: 10.1016/j.ejps.2018.10.001. Epub 2018 Oct 5.
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 (IC) of this nanoemulsion (480.7 μg/mL and 408 μg/mL) were 1.67 times and 1.98 times higher than those of its water solution (287 μg/mL and 206 μg/mL) after acting 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 (LD) of this nanoemulsion (23.25 mg/kg, 95% LD, 21.7-25.16 mg/kg) was 1.26 times higher than that of its water solution (18.59 mg/kg, 95% LD, 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.
本研究旨在提高藤黄酸的水溶性，降低其副作用，并增强其在体外和体内抗急性髓系白血病的疗效。该油包水型纳米乳（平均粒径 17.20±0.11nm，Zeta 电位 4.17±0.82mV）由吐温-80、丙二醇、角鲨烷和藤黄酸组成，溶解度提高了 4000 倍，通过伪三元相图制备而成。我们发现该纳米乳成功包封了藤黄酸，其稳定性好，在三种不同的磷酸盐缓冲液（pH=2.0、5.8 和 7.4）中均表现出明显的药物延迟释放效果。该纳米乳（480.7μg/mL 和 408μg/mL）对毒性标准细胞系（L929 细胞）作用 24h 和 48h 的半抑制浓度（IC）分别是其水溶液（287μg/mL 和 206μg/mL）的 1.67 倍和 1.98 倍。重要的是，急性注射毒性试验表明，该纳米乳（23.25mg/kg，95%LD，21.7-25.16mg/kg）的半数致死量（LD）是其水溶液（18.59mg/kg，95%LD，16.84-20.53mg/kg）的 1.26 倍。与混悬液相比，该纳米乳的生物利用度提高了 318.2%。此外，该纳米乳通过提高急性髓系白血病的存活率（MV4-11 移植小鼠）和降低白血病细胞（Jurket、HL-60 和 MV4-11 细胞）的半抑制浓度值，提高了其对急性髓系白血病的疗效。本研究表明，该纳米乳可能是一种有前途的急性髓系白血病治疗药物。
