| The purpose of this study aimed to prepare a high encapsulation efficiency, goodstability, safe and efficient avermectin naon liposome, and study its pharmacokineticsprocess, acute toxicity and clinical outcomes in the goats.1. To select the best method for AVMNL preparation. The best method of AVMNL preparation was selected from thin-film dispersion method and modified thin-film dispersion method by means of AVMNL entrapment efficiency. AVMNL was prepared by modified thin-film dispersion method, whose entrapment efficiency was 90.36%. The difference of modified thin-film dispersion method from thin-film dispersion method of entrapment efficiency was significant(P<0.05). The results showed thin-film dispersion method was the best method to prepare AVMNL.2. Preparation and physico-chemical property of avermectin naon liposome. Modified thin-film dispersion method was adopted to prepare the AVMNL. The optimal prescription for preparation of AVMNL were as follows: Lecithin︰Cholesterol=9︰1, AVM︰Lecithin=1︰10, p H of PBS is 7.0, conducting ultrasonic toward 5 minutes, evaporating at 40℃, and freezing and thawing 3 times. The appearance of AVMNL was milky liquid, spherical and distributed evenly under electron microscope. The average particle size was 198.2nm.3 The stability test of avermectin naon liposome. The content of avermectin nano liposome was measured by ultraviolet spectrophotometer. The stability of avermectin nano liposome was evaluated by thermal stability test and light stability test. The results showed that avermectin had the maximal absorption in 254 nm. It had a good linear range in 2 μg/m L- 32 μg/m L, and its mean recovery was(96.51±4.21)%,and RSD was 0.04%. That is, the method was accurate and reliable in measurement results. Avermectin nano liposome was not sensitive to heat, but its encapsulation efficiency was reduced in the light condition, so it should be protected from light.4 The Pharmacokinetic test of avermectin naon liposome. Pharmacokinetics in goats was studied after subcustaneous avermectin nano liposome injection. The avermectin nano liposomes concentration in serum was determined by HPLC after extracted from serum by ethyl acetate several times and evaporated through nitrogen stream. The pharmacokinetics characteristic of avermectin in goats was fitted with classic absorbable one-compartment model. Main pharmacokinetics parameters were as follows: absorption half time t1/2Ka=0.24±0.03 d, elimination half time t1/2Ke=6.74±0.80 d, the peak concentration Cm = 60.76 ± 5.62 ng/m L, area under the concentration time curve AUC = 664.35 ± 28.14 ng/m L) ? d, peak time Tp=1.20±0.08 d, and the efficacy could be maintained more than 30 days. As a result, the release effect of avermectin nano liposome has been determined, which can be used as long-acting formulations of avermectin in deeper study.5 The Acute toxicity test of avermectin nano liposome. After subcutaneous avermectin nano liposome in the pre-test, 100% mortality at a dose of 153.68mg/kg, the mortality rate of 0% at a dose of 57.97mg/kg. LD50 at a dose of 98.36mg/kg. LD50 95% confidence limit(FL) ranges: 83.39mg/kg~ 116.01mg/kg.6 Treatments in goats of avermectin nano liposome: Aivermectin nano 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, and compared to avermectin ordinary injection(0.2 mg/kg), avermectin nano liposome had a good release effect, and to 1.0 mg/kg dose of subcutaneous injection of the best. |
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