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Preliminary Research of the Drug Release from Superparamagnetic Isonniazide PELA Microspheres in Vitro and Vivo and Safety Evalution

Author: ZhangYuKun
Tutor: ZhuChaoMin
School: Chongqing Medical University
Course: Pediatrics
Keywords: Superparamagnetic Isoniazid PELA Release Acute Toxicity
CLC: R943
Type: Master's thesis
Year: 2011
Downloads: 10
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Abstract

Research purposes. Preparation of superparamagnetic isoniazid polylactic acid - polyethylene glycol copolymer (PELA) the microsphere the (superparamagnetic isoniazide Polylactide - polyethylene glycol copolymers microspheres, SPIPM) and research in the oscillating magnetic field effect in vitro release. 2 to study superparamagnetic isoniazid PELA microspheres in the oscillating magnetic field animals isoniazid release law. Preliminary study superparamagnetic isoniazid PELA microspheres security: superparamagnetic Fe3O4 nanoparticles (superparamagnetic Fe3O4 nanoparticle, SPFN) acute toxicity in mice. Research methods. Orthogonal experimental optimization of complex emulsion (W / O / W) solvent evaporation method superparamagnetic isoniazid PELA microspheres. Using UV spectrophotometry determination of SPIPM the encapsulation efficiency and drug loading amount. Using small cup method vitro microspheres of isoniazid release of grouping method Group: A superparamagnetic isoniazid PELA microspheres; Group: B superparamagnetic isoniazid PELA microspheres; C group: isonicotinoyl hydrazine PELA microspheres. A, C two groups before each sampling 30min using oscillating magnetic field interference 15min B group always without oscillating magnetic field interference. By double emulsion (W / O / W) solvent evaporation prepared SPIPM, select 18 New Zealand white rabbits were randomly divided into SPIPM applied oscillating magnetic field intervention group, SPIPM group and isoniazid solution group, these three groups were intramuscular injection. Every 15 minutes to take venous blood, the plasma concentration of isoniazid, isoniazid compared three groups of rabbit blood was determined by HPLC (High performance Liquid Chromatography, HPLC) release. 3. Chemical precipitation the prepared SPFN, transmission electron microscopy, and vibrating sample magnetometer SPFN determination of morphological observation and structural characterization. 60 mice by different modes of administration and dose, the random number table is divided into 3 groups (n = 20): (total dose: 2 104.8 mg / kg, volume: 25 ml / kg) by oral gavage group intraperitoneal injection group (total dose: 1578.6mg/kg volume: 20ml/kg), tail vein injection group (total dose: 438.5 mg / kg, volume: 10 ml / kg); each Another 10 mice to physiological saline as a control (n = 10). Observation of the general condition of the mice; fully automatic biochemical analyzer mice blood biochemical indicators; HE staining pathological changes of major organs; Wright's stained bone marrow tissue. Results: (1) release of super-paramagnetic microspheres of the group A in the oscillating magnetic field interference isoniazid was significantly higher than the release of isoniazid in the the oscillating magnetic intervention superparamagnetic group B microspheres. A group of superparamagnetic microspheres in the same oscillating magnetic field interference isoniazid release was significantly higher than in the C group of non-magnetic microspheres release of isoniazid. Compared with the simple injection of isoniazid, SPIPM can delay isoniazid release, plus the oscillating magnetic field, can be repeated to improve the animals SPIPM isoniazid release. 3 made of the particle size of 15 ~ 20 nm, a saturation magnetization of 21.431 emu / g, residual magnetization as 0.101 6 emu / g SPFN I SPFN 2 weeks later, the mice in each group were not killed, blood biochemical parameters were not statistically different (P gt; 0.05), major organ and bone marrow were no changes in inflammation, edema, degeneration, necrosis. Conclusion: 1. Vitro release, isoniazid PELA microspheres release, the oscillating magnetic field interference, can promote the release of superparamagnetic isoniazid PELA microspheres of isoniazid. In the absence of an external magnetic field, the microspheres with magnetic significantly affect the of PELA microspheres sustained release no. Vivo release, superparamagnetic isoniazid PELA microspheres with sustained-release, oscillating magnetic field significantly promote the release of isoniazid in vivo superparamagnetic isoniazid PELA microspheres. Homemade superparamagnetic Fe3O4 nanoparticles no significant acute toxicity in mice provide an experimental basis for further study of its set out as a carrier attached to the clinical application of biological security.

Preliminary Research of the Drug Release from Superparamagnetic Isonniazide PELA Microspheres in Vitro and Vivo and Safety Evalution

Abstract

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