Studies On The Freeze-drying Technology,Bioavailability And Preliminary Toxicity Of Albendazole Nano Powder

Objective: To investigate the freeze-drying technology, the bioavailability in rats, the acute toxicity and sub-chronic toxicity in mice of albendazole nano powder. To study the possible effects of bioavailability and toxicity on the drug after nanoparticlization. Methods:(1) The albendazole nano powder was prepared by freeze-drying technology. The main factors that affect the freeze-drying process(pre-freezing temperature, types, ratio and concentration of cryoprotectants)were investigated and optimized by single factor test.(2) Compared with the albendazole raw material, the relative bioavailability of albendazole nano powder was evaluated in rats.(3) Albendazole nano powder and albendazole raw material were once givern by lavage to contrast the possible change of acute toxicity in mice after nanoparticlization.(4) Mice were divided into 5 groups randomly, a blank control group, a group of albendazole raw material, three groups of albendazole nano powder were included. The drug was given orally with albendazole nano powder at a dose of 4000mg/kg, 1333 mg/kg, 400mg/kg for up to one month respectively, the continuous observation of 2 weeks was done. The daily activities were observed, the mice’s body weight, food intake, important organization coefficient, hematology and blood biochemistry were measured, and the histopathological changes were examined. Results:(1) The pre-freezing temperature is-20℃, the concentration of cryoprotectant is 4%, the ratio of cryoprotectant is glucose:mannitol = 3:7, then we can get the albendazole nano powder with loose appearance relatively, the size of albendazole nano powder is(304.60±2.05)nm, the Zeta potential is(-16.36±0.43)mV.(2) The albendazole nano powder in rats is consistent with two-compartment pharmacokinetic model. Compared with the raw material of albendazole, the relative bioavailability of albendazole nano powder is 157.03%.(3) The maximum tolerated dose of albendazole nano powder in mice after oral administration is 4000mg/kg, and the maximum tolerated dose of albendazole raw material is 3000 mg/kg.(4) In the experiment of sub-chronic toxicity, in addition to the high dose group of albendazole nano powder can influence the white blood cells, platelet and liver of the mice, the examination of hematology, blood biochemistry and histologic are normal in other groups. The daily activities and the organization coefficient in the blank control group, the group of albendazole raw material, the groups of albendazole nano powder are normal. Conclusion:(1) The albendazole nano powder prepared by lyophilization can obtain better appearance and smaller partical size than the albendazole raw material.(2) The albendazole nano powder can improve absorption rate of the drug, increase absorption of the drug and improve oral bioavailability of albendazole.(3) The albendazole nano powder dose not significantly increase acute toxicity of albendazole after nanocrystallization.(4) The high dose group of albendazole nano powder givern to mice for a month can reduce the number of white blood cells, platelets and have some influence on the liver in the mice, but they are back to normal in recovery phase. The toxicity of albendazole nano powder dose not significantly increase after nanocrystallization. The toxicity of albendazole nano powder and albendazole raw material are on the same level.