The Preparation And Evaluation Of Doxycycline Chitosan Nanoparticles Freeze-dried Powder

In this paper, Doxycycline Chitosan Nanoparticles (DC-CS-NPs) freeze-dried powder was prepared. The stability, release characteristics of DC-CS-NPs freeze-dried powder and DC raw material drug in vitro were researched. The pharmacokinetics and tissue distribution of them in channel catfish were studied.In the first, DC-CS-NPs freeze-dried powder was prepared by using freeze-drying and ionic gelation method. The preparation was optimized by orthogonal experimental design with encapsulation efficiency as the index. The particle morphology, size and potential were determined respectively by transmission electron microscopy, particle and potentiometric analyzer. The optimal preparation process of DC-CS-NPs was 2.5mg/mL chitosan solution,1.2mg/mL sodium tripolyphosphate solution,8mg doxycycline and pH 5.5. The DC-CS-NPs freeze-dried powder had a fluffy surface and good solubility. The DC-CS-NPs were discrete and uniform spheres under transmission electron microscopy with a mean particle size of (126.3±17.8) nm. The encapsulation efficiency and drug loading of DC-CS-NPs were (56.52±2.1)%and (16.83±0.27)%, respectively. The DC-CS-NPs freeze-dried powder has a feasible process of preparation.Secondly, the stabilities of DC-CS-NPs freeze-dried powder and DC raw material drug were studied. The ultraviolet, thermal and humid stabilities were measured. Compared to DC raw material drug, the ultraviolet degradation of DC-CS-NPs freeze-dried powder in 10d under bright lights of (4500±500) Lx decreased by 22.97%, and the thermal degradations in lOd decreased by 18.72% at 40℃and 31.41% at 60℃, while the humid degradations in 10d decreased by 20.45% at 75% and 26.90% at 92.5%. The DC-CS-NPs freeze-dried powder has characteristic of good stabilities.Thirdly, the release characteristics of DC-CS-NPs freeze-dried powder and DC raw material drug in vitro were studied. Results showed that the DC-CS-NPs freeze-dried powder had a significant slow-release characteristic. The release speed from fast to slow was artificial gastric juice, artificial intestinal juice and pH7.4 buffer phosphate. When the pH of artificial gastric juice was from 2 to 4, the release speed of freeze-dried powder decreased as the pH of artificial gastric juice increased; In the artificial gastric juice, artificial intestinal juice and pH7.4 buffer phosphate, the release of DC raw material drug were similar which could completely dissolute in 1 hour.Finally, the pharmacokinetics and tissue distribution of DC-CS-NPs freeze-dried powder and DC raw material drug in channel catfish were researched. After a single oral administration at a dose of 20 mg·kg-1 at (25±1)℃, not only the drug concentration of plasma and tissues but also pharmacokinetic parameters of plasma in Channel Catfish (Ictalurus punctatus) were changed. The double-peak phenomenons of plasma, liver, kidney, muscle (added skin) were turned into single-peak. Compared to DC raw material drug, the peak concentrations (Cmax) of tissues decreased and the peak times (Tmax) prolonged. The concentration-time course of DC in plasma can be described by a two-compartment open model after a single oral administration by using the 3p97 software. The Tmax and terminal elimination half-life (T1/2β) of DC-CS-NPs freeze-dried powder in plasma prolonged, and the Cmax decreased. The area under concentration-time curve (AUC) was larger. The DC-CS-NPs freeze-dried powder obviously changed the distribution of plasma and tissues. The drug concentration of liver and kidney decreased and the toxicity of drug to liver and kidney cell was much smaller. The DC-CS-NPs freeze-dried powder will become to an ideal DC new formulation.