Preparation And Properties Of Drug-loaded Systems For Controlled Release Ivermectin.and The Effacy Test Of A New Anticoccidial Drug In Chicken

As a kind of antiparasitic drug,ivermectin has many outstanding characteristics,such as high insecticidal activity,broad spectrum,being applied to a variety of animals,multiple administration routes including through the mouth,skin and muscle,application safety in recommended dose without poisoning effect,no teratogenesis and carcinogenesis effect.Hollow silica nanoparticle,a new type of inorganic porous nano-material,has the characteristics of large specific surface area,high mechanical strength and strong thermal stability.For its good biocompatibility,it has been widely applied as catalyst carrier,enzyme immobilization,biological markers,especially in the area of drug-loaded study,such as drug sustained and controlled release,drug targeting and intelligent drug delivery.In our research,insoluble ivermectin was dissolved into ethanol with different volume ratio to prepare the ivermectin-SiO₂ sustained release particle of different theoretical drug-loading rate,including 1%,2% and 5%.The actual drug-loading rate of ivermectin-SiO₂ was detected by thermogravimetric analysis?TGA?and ultraviolet spectrophotometer?UV?separately.The degree of drug adsorption and release was determined in vitro subsequently.When the volume ratio of ethanol and silica solution was 2.5:1,the actual drug-loading rate of ivermectin-SiO₂ by TGA was 0.59%,1.51% and 3.07%,corresponding respectively to the theoretical drug-loading rate 1%,2% and 5%.When the volume ratio was 3:1,the actual drug-loading rate was 0.24%,1.09% and 2.36% accordingly.On the other hand,the standard curve equation y=34471.87631x+ 0.00162?R2=0.99991?,established by ultraviolet spectrophoto-meter under 245 nm,was used to calculate the actual drug-loading rate and encapsulation rate.As the volume ratio was 2.5:1,the actual drug-loading rate figured out based on the above equation was 0.63%,1.58% and 3.25%,the encapsulation rate was 78.24%,96.85% and 75.07%.However,as the volume ratio was 3:1,the actual drug-loading rate was 0.24%,1.05% and 2.03%,the encapsulation rate was 25.59%,55.93% and 5.94% respectively.The above results obtained by the two methods showed that the actual drug-loading rate and encapsulation rate was better when the volume ratio of ethanol to silica solution was 2.5:1 than of 3:1.It was found that the ivermectin reached dissolution equilibrium at 114 hour,the ivermectin-SiO₂ had a significant sustained release effect.The ivermectin-SiO₂ with theoretical drug-loading rate of 1% and 2% reached dissolution equilibrium at about 150 hour,while the accumulative releasing ratio of 5% loaded-drug was just 50% at this time point.The accumulative releasing ratio increased with the drug-loaded amount.However it always cannot exceed the ratio of ivermectin.Together,it can be concluded that the design of the drug-loaded systems for controlled release of ivermectin is feasible.And the pharmaceutical preparation is expected to applied to clinical practice for the simple procedure and low cost.Avian coccidiosis,caused by Eimeria protozoan,is an intestinal parasitic disease that often causes huge economic losses to the poultry industry because of its high morbidity and mortality.The mortality rate of the disease is usually high,especially in the 15 to 50-day age chicks,the rate can be up to 80%.Once infection,it disturbs the growth of chicks for a long time even if they are cured.With high efficiency,low toxicity,broad spectrum anticoccidial effect,diclazuril is popular among the famers.However,diclazuril is insoluble in water,which is inconvenient for clinical medication.In order to test the anticoccidial efficacy of hydrosoluble diclazuril premix that is developed by a company,the 15-day age AA+ broilers were inoculated with 1×105 sporulated oocysts of E.tenella which were resistant to diclazuril through crop.Three drug treatment groups were designed in our research: hydrosoluble diclazuril premix of 0.5mg/kg,1mg/kg,2mg/kg,diclazuril premix of 1mg/kg,2mg/kg,Nicarbazin premix of 125mg/kg.The results showed that the anticoccidial index?ACI?of the six groups were 67?96?95.74?110.53?95.61?113.97 respectively,which were all bellow 160.This indicated that the efficacy on coccidiosis of the three kinds of drugs was poor.Although the hydrosoluble diclazuril had higher absorption rate,it also cannot kill coccidial effectively,even with increased dose.What's more,the E.tenella strain used in our research was resistant to Nicarbazin.