阴离子纳米脂质体的临床前毒性评价

IF 9.9 Q1 MATERIALS SCIENCE, COMPOSITES
Amir Abbas Momtazi-Borojeni , Mahdi Hatamipour , Mohammad Reza Sarborji , Mahmoud Reza Jaafari , Amirhossein Sahebkar
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引用次数: 0

摘要

目的评估含有[氢化大豆磷脂酰胆碱(HSPC)]和[1,2-二硬脂酰-sn-甘油-3-磷酸甘油(DSPG)]的阴离子纳米脂质体制剂的体内毒性。 方法采用脂膜水合法制备阴离子纳米脂质体制剂。为了评估阴离子纳米脂质体的毒性,给雌雄白化小鼠静脉注射阴离子纳米脂质体制剂(100 μmol/kg),持续四周。在最后一次注射四周后,采用亚急性方案进行毒性研究。为此,测定了血浆中的血脂指标、尿素、肌酐、谷草转氨酶、谷丙转氨酶、谷草转氨酶和空腹血糖(FBG)。为了评估组织病理学改变,使用苏木精和伊红(H&E)染色法研究了包括心脏、肝脏、肾脏、脾脏和大脑在内的重要器官的组织。结果结果显示,与对照组小鼠相比,脂质体治疗组小鼠的总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、肌酐、尿素、谷草转氨酶、谷丙转氨酶和谷草转氨酶均无显著变化。然而,与相应的对照组小鼠相比,经脂肪族处理的雄性小鼠和雌性小鼠的血浆甘油三酯水平分别明显下降(64.5 ± 15.3 mg/dL,p = 0.001)和(58.75 ± 15.3 mg/dL,p = 0.002)。与对照组雄性小鼠相比,经脂质体处理的雄性小鼠的 FBG 水平明显增加了 154 ± 20 mg/dL,p = 0.001。与对照组雄性小鼠相比,经脂质体处理的雄性小鼠的 PAB 水平明显下降了 12 ± 4.2 HK,p = 0.03。本研究结果表明,含 DSPG 的纳米脂质体制剂对健康小鼠的重要器官功能和血液中的生化生物标志物水平无明显不良影响。不过,还需要进一步研究,以找到与糖尿病风险相关的 DSPG 脂质体的安全剂量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Preclinical toxicity assessment of anionic nanoliposomes

Aim

To evaluate the in vivo toxicity of the anionic nanoliposome formulation containing [hydrogenated soy phosphatidylcholine (HSPC)] and [1,2-distearoyl-sn-glycero-3- phosphoglycerol (DSPG)].

Methods

The anionic nanoliposome formulation was prepared by the lipid film hydration method. To assess the toxicity of anionic nanoliposomes, male and female albino mice were weakly treated with intravenous injection of the formulation (100 μmol/kg) for four weeks. The toxicity study was performed by the subacute protocol, four weeks after the last injection. To this end, the plasma levels of lipid indexes, urea, creatinine, AST, ALT, ALP, and fasting blood glucose (FBG) were measured. To evaluate histopathological alterations, the tissues of the vital organs including the heart, liver, kidneys, spleen, and brain were studied using hematoxylin & eosin (H&E) staining.

Results

The results showed nonsignificant changes in total cholesterol, LDL-C, HDL-C, creatinine, urea, AST, ALP, and ALT in the liposome-treated mice when compared with control mice. However, plasma levels of triglycerides were significantly decreased (by 64.5 ± 15.3 mg/dL, p = 0.001) and (by 58.75 ± 15.3 mg/dL, p = 0.002) in the liposome-treated male and female mice, respectively, when compared with corresponding control mice. The FBG level was significantly increased by154 ± 20 mg/dL, p = 0.001 in the liposome-treated male mice when compared with the control male mice. The PAB level was significantly decreased by 12 ± 4.2 HK, p = 0.03 in the liposome-treated male mice when compared with the control male mice. Histological examination of vital organs indicated no significant differences in tissue damage between the liposome-treated and control mice.

Conclusion

The findings of the present study indicated that DSPG-containing nanoliposome formulation exerted no significant adverse effects on the function of vital organs and blood levels of biochemical biomarkers in healthy mice. However, further investigations are needed to find a safe dose of DSPG liposomes concerning the risk of diabetes.

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来源期刊
Advanced Industrial and Engineering Polymer Research
Advanced Industrial and Engineering Polymer Research Materials Science-Polymers and Plastics
CiteScore
26.30
自引率
0.00%
发文量
38
审稿时长
29 days
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