Preclinical toxicity assessment of anionic nanoliposomes

Abstract

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.