| Ceftiofur sodium is widely used in the veterinary clinics as an animal-specific broad-spectrum antibiotic. Chitosan nanoparticle shows slow release, controlled release and targeted release properties in drug delivery and has been gradually concerned by pharmaceutical researchers. In order to prepare novel sustained-release and efficient ceftiofur sodium drug delivery, the ceftiofur sodium-chitoan nanoparticle (CNP) was prepared by ionic crosslinking method and the related properties were studied.The content detection method was established by ultraviolet spectrophotometry for determining the encapsulation efficiency and drug loading. The regression equation of concentration and absorbance of ceftiofur was:y= 0.0382x-0.0068, r=0.9999. The linear range was 6-22μg/mL. The intro-day and inter-day precision was 0.35～0.94% and 0.60～1.28%, respectively. The recovery rate was 99.14～100.17%.CNP were prepared by ionic crosslinking method. Using encapsulation efficiency as index of examination, the uniform design experiment was used to optimize the prescripton of CNP. The optimal formulation of CNP was:chitosan:4mg/mL; sodium tripolyphosphate (TPP):1.5mg/mL and ceftiofur sodium:2.0mg/mL.For evaluating quality of CNP, the appearance was observed by transmission electron microscopy, the particle size and distribution was detected by laser particle size analyzer, encapsulation efficiency and drug loading efficiency was determined by dialysis method, in vitro release profile of ceftiofur sodium was determined by shaking method at constant temperature. It was found that the optimal CNP showed good appearance arid uniform size. The size was about 179.4nm, mean encapsulation and mean loading rate was 84.21% and 6.69%, respectively. The in vitro release experiment showed ceftiofur sodium was released above 90%, meanwhile CNP released 10% at 4h. CNP released 33% at 30h. CNP remarkably reduced the release rate of ceftiofur sodium compared to crud drug.Ceftiofur sodium in plasma was determined by high performance liquid chromatography. Calibration curve was linear between 2.78 and 14.63μg/mL. y =4484.0559+30245.2340x, with the correlation coefficient r=0.9995. The intro-day and inter-day precision was 0.97～1.64% and 1.15～2.04%, respectively. The recovery was in the range of 96.07～98.88%.Degradation kinetics test in plasma showed ceftiofur sodium was unstable in rabbit plasma. The residue concentration of ceftiofur sodium was 22.9% while CNP was 37.6% at 4h. Their stability improved after removing plasma protein, the residue concentration was 40.2% and 78.4%, respectively.In vitro bacteriostatic test showed the MIC of ceftiofur sodium and CNP against E.coli was 1.3 and 1.0μg/mL, respectively. The MIC of ceftiofur sodium against S. aureus was 1.0μg/mL while CNP was 0.8μg/mL. The antibacterial effect of CNP was better than ceftiofur sodium against E.coli and S. aureus.The preparation method of CNP was handy and simple, and the quality was adjustable. The quality evaluation, degradation kinetics in plasma and bacteriostatic test indicated that CNP obtained slower release, better stability and higher bacteriostatic effect. It is potential to be used as a good carrier in drug delivery system.
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