Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran,
Students Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Int J Nanomedicine. 2018 Nov 9;13:7363-7374. doi: 10.2147/IJN.S181896. eCollection 2018.
The aim of this study was to prepare curcumin nanoemulsion (CR-NE) to solve the problems associated with poor water solubility and low bioavailability of CR and to test its efficiency in the treatment of acute and chronic toxoplasmosis in mouse models.
CR-NE 1% was prepared using spontaneous emulsification by soybean as oil phase; a mixture of Tween 80 and Tween 85 as surfactant; ethanol as cosurfactant and distilled water. Particle size and zeta potential of NE were assessed using Nano-ZS90 dynamic light scattering. Stability testing of NE was assessed after storage for 2 months at room temperature. In vivo experiments were carried out using 50 BALB/c mice inoculated with virulent RH strain (type I) and 50 BALB/c mice inoculated with avirulent Tehran strain (type II) of and treated with CR-NE (1% w/v), CR suspension (CR-S, 1% w/v), and NE without CR (NE-no CR).
The mean particle size and zeta potential of CR-NE included 215.66±16.8 nm and -29.46±2.65 mV, respectively, and were stable in particle size after a three freeze-thaw cycle. In acute phase experiment, the survival time of mice infected with RH strain of and treated with CR-NE extended from 8 to 10 days postinoculation. The differences were statistically significant between the survival time of mice in CR-NE-treated group compared with negative control group (<0.001). Furthermore, CR-NE significantly decreased the mean counts of peritoneum tachyzoites from 5,962.5±666 in negative control group to 627.5±73 in CR-NE-treated mice (<0.001). Growth inhibition rates of tachyzoites in peritoneum of mice receiving CR-NE, CR-S, and NE-no CR included 90%, 21%, and 11%, respectively, compared with negative control group. In chronic phase experiment, the average number and size of tissue cysts significantly decreased to 17.2±15.6 and 31.5±6.26 µm, respectively, in mice inoculated with bradyzoites of Tehran strain and treated with CR-NE compared with that in negative control group (<0.001). Decrease of cyst numbers was verified by downregulation of BAG1 in treatment groups compared with negative control group with a minimum relative expression in CR-NE (1.12±0.28), CR-S (11.76±0.87), and NE-no CR (14.67±0.77), respectively, (<0.001).
Results from the current study showed the potential of CR-S and CR-NE in treatment of acute and chronic toxoplasmosis in mouse models for the first time. However, CR-NE was more efficient than CR-S, and it seems that CR-NE has a potential formula for the treatment of acute and chronic toxoplasmosis, especially in those with latent bradyzoites in brain.
本研究旨在制备姜黄素纳米乳(CR-NE),以解决 CR 水溶性差和生物利用度低的问题,并在小鼠模型中检测其治疗急性和慢性弓形虫病的疗效。
采用大豆为油相、吐温 80 和吐温 85 的混合物为表面活性剂、乙醇为助表面活性剂、蒸馏水自发乳化制备 1%CR-NE。采用 Nano-ZS90 动态光散射法测定 NE 的粒径和 Zeta 电位。室温下储存 2 个月后,对 NE 的稳定性进行评价。使用 50 只 BALB/c 小鼠接种强毒 RH 株(I 型)和 50 只 BALB/c 小鼠接种弱毒 Tehran 株(II 型)进行体内实验,并分别用 CR-NE(1%w/v)、CR 混悬剂(CR-S,1%w/v)和不含 CR 的 NE(NE-no CR)处理。
CR-NE 的平均粒径和 Zeta 电位分别为 215.66±16.8nm 和-29.46±2.65mV,经过三次冻融循环后粒径稳定。在急性感染实验中,感染 RH 株的小鼠的存活时间从接种后 8 天延长至 10 天。与阴性对照组相比,CR-NE 治疗组小鼠的存活时间差异有统计学意义(<0.001)。此外,CR-NE 显著降低了阴性对照组 5962.5±666 个腹膜内速殖子的平均计数,降至 CR-NE 治疗组的 627.5±73 个(<0.001)。接受 CR-NE、CR-S 和 NE-no CR 的小鼠腹膜内速殖子的生长抑制率分别为 90%、21%和 11%,与阴性对照组相比。在慢性感染实验中,与阴性对照组相比,感染 Tehran 株的 bradyzoites 的小鼠的组织包囊数量和大小分别显著减少至 17.2±15.6 和 31.5±6.26μm(<0.001)。与阴性对照组相比,治疗组的 BAG1 下调证实了囊数量的减少,以 CR-NE(1.12±0.28)、CR-S(11.76±0.87)和 NE-no CR(14.67±0.77)的最小相对表达率为最低(<0.001)。
本研究首次表明 CR-S 和 CR-NE 有潜力治疗小鼠模型中的急性和慢性弓形虫病。然而,CR-NE 比 CR-S 更有效,而且 CR-NE 似乎具有治疗急性和慢性弓形虫病的潜在配方,特别是在那些有潜伏在大脑中的 bradyzoites 的患者中。