Preparation And Properties Of FFC/Hydroxypropyl Chitosan-Long Chain Carboxylic Acid Nano-Micelles

Florfenicol（FFC）has a wide antibacterial spectrum and leaves less residue in animals,so it is safer than chloramphenicol.FFC’s poor water solubility caused numerous problems in veterinary clinical applications.In order to solve this problem,a new type of chitosan derivative nano-material—HPCH-SA nano-micelle—was prepared in this paper.Hydroxypropyl and stearic acid were grafted onto CS to synthesize HPCH-SA polymer,and then HPCH-SA polymer was self-assembled into HPCH-SA nano-micelles by the dialysis-ultrasound method.The raw materials,intermediates,HPCH-SA polymers,HPCH-SA nano-micelles,and FFC/HPCH-SA nano-micelles were characterized by FT-IR,~1H NMR,and XRD.The results showed that the HPCH-SA nano-micelles were spherical,the surface was smooth and wrinkle-free,and the Zeta potential was 35.1 m V when the particle size was 225.42 nm.When the molar ratio of FFC:HPCH-SA blank nano-micelle was 1:1,it had the best drug loading（33.09%）and entrapment efficiency（79.02%）.In in vitro tests,FFC/HPCH-SA nano-micelles have obvious antibacterial activity,and the release of drug FFC in drug-loaded nano-micelles was called sustained release.The hemolysis experiment showed that the nano-micelles had excellent antihemolytic properties.The parameters of FFC in rats were as follows:the area under the drug-time curve AUC_（0-24）was 28.546±0.821 mg/L·h,the average retention time MRT_（0-24）was4.24±0.187 h,the biological half-life t_1/2zwas 5.39±0.722 h,the peak time T_maxwas1.5 h,the clearance rate CLz/F was 1.026±0.035 L/h/kg,and the apparent distribution volume Vz/F was 7.966±0.988 L/kg.The maximum blood solubility Cmax was7.993±0.137 mg/L,and the oral bioavailability F was 93.157±1.218%,indicating that FFC could be absorbed widely,eliminated slowly,had a long half-life and could be maintained at a high concentration for a long time after reaching the maximum blood concentration,and had a good oral bioavailability.The results showed that amphiphilic chitosan derivative nano-micelle HPCH-SA could effectively increase the solubility of hydrophobic drugs in body fluids,prolonged the action time of drugs,and improved the bioavailability of drugs,which had a broad application prospect.