Studies On The Preparation Of Doxycycline Liposome And Its Pharmacokinetics

To bring into full play doxycycline efficacy of medicine, or to extend the effective blood concentration time, reducing drug consumption, increasing drug treatment index, lower drug toxicity, and changes in administration to avoid the emergence of such purposes. The toxicology pharmacokinetics and clinical treatment of liposomal doxycycline in the animal body were studied, which had the highest encapsulation efficiency and best stability. To optimize the preparing technique and prescription, doxycycline liposomes were prepared by the thin-film hydration and ultrasonic technique to investigate the effect of velocity, organic solvent and vibrated speed of aether on its encapsulation efficiency and stability. The optimized preparing techniques were determined: methanol,chloroform as organic solvent, the optimum prescription preparation of doxycycline liposome were selected with orthogonal design: lecithin: cholesterol= 1:20; doxycycline (lecithin + cholesterol)= 1:8; PH of PBS is 7.4, organic solvent:PBS=3:l. The results indicated the prepared liposome under the test conditions had the highest encapsulation rate (68.8±1.38%) and best stability.The safety evaluation of liposomal doxycycline was conducted by the acutetoxicity tests in rats. Sixty KM rats were randomly divided into 4 groups. There levels of liposomal doxycycline were injected for 4 week in succession and physiological saline was injected as control group. The growth performance, hematological indicators, serum biochemical and histopathological examination were conduced. The results indicated that the LD₅₀ of liposomal doxycycline are higher than the LD50 of doxycycline, and no difference were observed between trailed and control group. The results indicated that toxicity of Hposomeal doxycycline was significantly lower than that of convertional doxycycline.The experiment was conducted in rabbit's body to investigate pharmacokinetics about liposomal doxycycline. A dose of 0.5mg/kg Hposomeal doxycycline was given to rabbit's and blood samples were collected at different time to measure the drug concentration. The results showed that drug concentration-time curve conformed to one compartment model and its main pharmacokinetical parameters were t_1/2β7.6060h, CL0.3973 mL/kg,AUG14.5884 h.mg/mL, which indicated the drug effects time had been extended effectively.