Preliminary Research Of The Drug Release From Superparamagnetic Isonniazide PELA Microspheres In Vitro And Vivo And Safety Evalution

Objective:1. To prepare superparamagnetic isoniazide PELA microspheres,and to research the drug release from superparamagnetic isoniazide PELA microspheres under the interference of oscillating magnetic field in vitro.2. To research the release rules of isoniazid carried by superparamagnetic isoniazide PELA microspheres under the interference of oscillating magnetic field in vivo.3. To preliminarily research the safety of superparamagnetic isoniazide PELA microspheres by observing the acute toxicity of superparamagnetic Fe3O4 nanoparticles on mice.Methods:1. Superparamagnetic isoniazide PELA microspheres were prepared by double-emulsion/solvent evaporation method which was optimized by the orthogonal experiment. The entrapment efficiency and drug-loading rate of SPIPM were determined by ultraviolet spectrophotometry. Small cup method was used to study the drug release of SPIPM In vitro. Three groups were divided. Group A: superparamagnetic isoniazide PELA microspheres, Group B: superparamagnetic isoniazide PELA microspheres, Group C: isoniazid PELA microspheres. Group A and C were by oscillating magnetic field for 15 minutes 30 minutes before each sampling . Group B was not interfered by oscillating magnetic field.2. SPIPMs were prepared by solvent evaporation with complex emulsification. 18 New Zealand white rabbits were randomly divided into 3 groups to receive intramuscular injection, SPIPM was injected and oscillating magnetic field was given; SPIPM was injected, without oscillating magnetic field; Isoniazid solution was injected. Every fifteen minutes take venous blood, the blood concentration of isoniazid was tested by high performance liquid chromatography. To compare isoniazid release in the three groups of rabbits.3.The superparamagnetic Fe3O4 nanoparticles were obtained by means of chemical coprecipitation,and their morphology and structural characterization were observed and determined by transmission electron microscope and vibratory sample magnetometer, etc. According to different ways and dosage of the drug 60 mice were randomly divided into oral administration (with a total dose of 2000 mg/ kg and a volume of 25 ml/ kg, n = 20), intraperitoneal injection (with a total dose of 1625 mg/ kg and a volume of 20 ml/ kg, n = 20) and caudal vein injection (with a total dose of 438. 5 mg/ kg and a volume of 10 ml/ kg, n = 20) groups. Another 10 mice in each group receiving the same dose of normal saline via the same pathway served as the controls ( n = 10). The general condition of mice was observed during the experiment, the major blood biochemical indicators were analysed by the automatic biochemical analyzer, and the pathological changes of major organs and the myeloid tissue were observed by H-E staining and Wright staining respectively.Results:1. Isoniazid release from superparamagnetic microspheres in Group A adding oscillating magnetic field was significantly higher than that from superparamagnetic microspheres in Group B without oscillating magnetic field. Under the same interference of oscillating magnetic field, isoniazid release from superparamagnetic microspheres in Group A was significantly higher than that from nonmagnetic microspheres in Group C.2. Compared with the group receieved only isoniazid solution, the time of isoniazid release was longer in the groups receieved SPIPM. Oscillating magnetic field can repeat increase the release of isoniazid carried by SPIPMs in vivo.3. prepared SPFNs with the particle diameter 15-20 nm , a saturated magnetization of 21.431 emu/g, and a remanent magnetization of 0.1016 emu/g. There was no death of mice during the observation. There was no significant difference in blood biochemical indicators between mice of different groups and between each experiment group and their corresponding control group. No inflammation, edema, degeneration and necrosis were seen in the major organs and the bone marrow.Conclusions:1. In vitro, isoniazide PELA microspheres appeared slow-releasing potential. The interference of Oscillating magnetic field significantly increased the release of isoniazid carried by superparamagnetic isoniazide PELA microspheres in vitro. PELA microspheres was effected no significant by the microspheres whether to have magnetic without Oscillating magnetic field2. In vivo, superparamagnetic isoniazide PELA microspheres appeared slow-releasing potential. The interference of oscillating magnetic field significantly increased the release of isoniazid carried by superparamagnetic isoniazide PELA microspheres in vivo.3.Superparamagnetic Fe3O4 nanoparticles cause no acute toxicity on mice,which warrants further study on their role as a carrier in clinical application Biological safety of carrier-attached drugs.