Safety Evaluation of Berberine-loaded Liposomes in Rats

Berberine (BBR)-loaded liposomes have endogenous lipid-lowering and exogenous lipid-lowering, which are reported in our previous studies. However, the safety profile of BBR-loaded liposomes has not been disclosed. In this study, experiments were carried out to evaluate the potential toxicity of BBR-loaded liposomes through the methods of acute and sub-chronic oral administration in rats. Acute toxicity studies were conducted according to the Organization for Economic Cooperation and Development (OECD) guidelines No. 420 on female Wistar white rats for 14 days with a single dose of BBR-loaded liposomes equivalence with  2000 mg of BBR/kg body weight (b.w) for sighting study; 2000 mg of BBR/kg and 5000 mg of BBR/kg b.w for the main study. Sub-chronic toxicity studies were performed according to OECD guidelines No. 407 on Wistar white rats (both sexes) with daily oral doses of BBR-loaded liposomes equivalence with 150 mg, 450 mg of BBR/kg b.w for 28 days consecutively. The study results showed no signs of acute toxicity. In the sub-chronic toxicity study, there was no significant change in the general characters, body weight, and organ weights of the treated group of rats when compared to the control group of the same sex. Hematological, biochemical, and histological parameters also showed no toxic effects of BBR-loaded liposomes on rats. The overall findings of this study indicated that LD50 of BBR-loaded liposomes was above 5000 mg/kg; the doses of 150 mg and 450 mg of BBR/kg b.w could be considered safe doses of BBR-loaded liposomes for oral administration.