| Tuberculosis is one of the ten major threats to human life. Traditional anti-tuberculosis drugs used in the treatment of tuberculosis have many deficiencies,such as drug resistance, short cycle time and certain side effects. At present, an important means to solve the defects of traditional drug is to develop a new anti-tuberculosis pharmaceutical preparation with a slow release function. This pharmaceutical preparation can increase the circle time of the drug in the body and improve the drug utilization rate, thus reducing the side effects of the drug.Isoniazid (INH) is one of the most important antimicrobial agents in the course of tuberculosis treatment, and has the advantages of good selectivity and strong antibacterial activity. The development of magnetic nanocomposite microspheres with active targeting, long circulation and excellent antimicrobial (isoniazid) is of great significance in the treatment of tuberculosis.In this paper, Fe3O4 was selected as the magnetic material,chitosan (CS) and synthetic polymer hyperbranched polyester (HBPE-DDSA) were used as carriers. The magnetic Fe3O4 nanoparticles was synthesized by one-step method and was full characterized by TEM, XRD, FTIR and TGA. The experimental conditions were screened by orthogonal experiment and the performance of microspheres was characterized by SQUID, in vitro sustained release assay and cytotoxicity assay. The main research contents are listed as follows:(1) Preparation of Fe3O4/CS/INH composite drug-loaded microspheres. The optimum conditions were as follows: the concentration of CS solution (30 mL) was 1 g / L, the amount of INH was 0.2 g, the addition amount of FeCl3 · 6H2O and FeCl2 ·4H2O were 0.134 g and 0.364 g, respectively. The volume of TPP solution and ammonia were both 15 mL. The drug loading and entrapment efficiency of Fe3O4/CS/INH composite microspheres prepared under the experimental parameters were 40.48% and 41.07% respectively. The TEM, XRD, FTIR and TGA were used to characterize the preparation of composite microspheres. The components of the composite microspheres are connected by physical electrostatic interaction, and the particle size of the composite microspheres is 4-7 nm, which has good magnetic properties.(2) Preparation of Fe3O4/HBPE-DDSA/INH composite drug-loaded microspheres. The optimum conditions were as follows: the addition amount of HBPE-DDSA was 0.05 g, the amount of ethanol was 15 mL, the amount of INH was 0.25 g, the addition of pure water was 15 mL of, the addition of FeCl3·6H2O and FeCl2·4H2O were 0.728 g and 0.268 g. The loading and encapsulation efficiency of Fe3O4/HBPE-DDSA/INH composite microspheres were 42.12% and 68.33%respectively. The TEM, XRD, FTIR and TGA were used to characterize the composite microspheres. The components of the composite microspheres are connected by physical electrostatic interaction, and the particle size the composite microspheres is 4?7 nm, which has good magnetic properties.(3) The drug release experiments and SQUID of Fe3O4/CS/INH and Fe3O4/HBPE-DDSA/INH composite microspheres were carried out. The results showed that the two microspheres had properties of slow release and pH sensitivity,and the hysteresis curve proved that the magnetic properties of the composites are satisfactory, and it can be seen that the two composite microspheres possess the ability of magnetic targeting slow- release and pH controlled- release .(4) In the cytotoxicity test of Fe3O4/CS/INH and Fe3O4/HBPE-DDSA/INH composite microspheres, the growth status of the cells were good and the relative survival rates of the cells were more than 90%, indicating that the microspheres had no obvious cytotoxicity and the biocompatibility of the material was good.These results show that the magnetic Fe3O4/HBPE-DDSA/INH and Fe3O4/HBPE-DDSA/INH composite drug-loaded microspheres have a good application prospect in the treatment of tuberculosis. |
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