Preparation Of Ivermectin Liposome And Its Pharmacokinetics And Treatments In Goats

The purpose of this study was to prepare a high encapsulation efficiency ivermectin liposome that is stable, secure and efficient and to study pharmacokinetics process of ivermectin liposome in the goats.1. Preparation of ivermectin liposome: Modified thin-film dispersion method was adopted to prepare the IVML. The optimal prescription for preparation of IVML were as follows: Lecithin︰Cholesterol=9︰1, IVM︰Lecithin=1︰10, pH of PBS is 7.0, conducting ultrasonic toward 5 minutes, evaporating at 40℃, and freezing and thawing 3 times. Its diameter was distributed mainly in 86～115 nm and the average grain size was (91.8±1.5) nm. The encapsulation efficiency of prepared IVML has reached (90.71±0.8)%(n=3), and it was stable fo heat, but unstable for light. The results shows the encapsulation efficiency was comply with a standard.2. The physico-chemical property of ivermectin liposome: The physico-chemical property was detected by electron microscope, photon correlation spectroscope. The results showed that ivermectin liposome was milky white liquid. Its average diameter was (91.8±1.5) nm. The disposition of diameter was narrow and uniformity.3. The stability of ivermectin liposome: The content of ivermectin liposome were measured by ultraviolet spectrophotometer. The stability of ivermectin liposome was evaluated by centrifuging, acceleration, light and long-term. The results showed that ivermectin had the maximal absorption in 250 nm. It had a good linear range in 2μg/mL~48μg/mL, its mean recovery was 97.60%, and its average entrapment efficiency was (90.71±0.8)%. The method of determining was convenient, sensitive, accurate and suitable for determining the entrapment efficiency and content of the liposome. The appearance and content of liposome did not change by constant temperature acceleration and long-term.4. The acute toxicity experiment of ivermectin liposome: The safety of ivermectin liposome was evaluated by acute toxicity experiment. The results showed that the accmumulation LD50 of the ivermectin liposome test on mouse was 103.04 mg/kg.5. Pharmacokinetics of ivermectin liposome in goats: Goats were treated with ivermectin liposome (0.2 mg/kg) for hypodermic injection. The concentrations of ivermectin liposome in blood were determined by high performance liquid chromatography(HPLC). Concentration-time is fitted by method of residual and pharmacokinetic parameters is calculated. The results showed that the two-compartment open model with absorption factor adequately describes concentrations of ivermectin liposome(0.2 mg/kg)for hypodermic injection in 6 goats'blood disposition and the best concentration-time equations are: C=41.2768·e-0.6564·t+4.9744·e-0.0809·t-46.2512·e-0.7244·t. The primary pharmacokinetic parameters of ivermectin liposome are: t1/2Kα=0.499±0.264 d, t1/2Ke=6.859±1.002 d, AUC=77.066±17.315 ng·mL-1·d. It will be seen that the distribution of ivermectin liposome in vivo is rapid, and the elimination of thiamphenicol nanoemulsion in vivo is slowly and relatively.6. Treatments in goats of ivermectin liposome: Iivermectin liposome was administrated to goats by subcutaneous injection and divide them into three different dose (0.2 mg/kg, 0.5 mg/kg, 1.0 mg/kg)for de-worming, liposomal ivermectin and the ivermectin injection (0.2 mg/kg) were carried on contrast to experiment, observing the treatment result. The results of treatment showed the cure rates of high and low dose liposomal ivermectin were significantly higher than that of conventional ivermectin, liposomal ivermectin can reduce consumption, prolong drug effect and cut down medicine remaining as well and to 1.0 mg/kg dose of subcutaneous injection of the best.