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姜黄素纳米乳剂作为一种新型化学药物治疗小鼠急、慢性弓形虫病。

Curcumin nanoemulsion as a novel chemical for the treatment of acute and chronic toxoplasmosis in mice.

机构信息

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.

出版信息

Int J Nanomedicine. 2018 Nov 9;13:7363-7374. doi: 10.2147/IJN.S181896. eCollection 2018.

Abstract

BACKGROUND

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.

MATERIALS AND METHODS

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).

RESULTS

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).

CONCLUSION

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.

摘要

背景

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。

材料与方法

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。

结果

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)。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3180/6233476/0f779a80cbe5/ijn-13-7363Fig1.jpg

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