Study On The Controllable Preparation And Performance Of Fe₃O₄/HBPE-SA/INH Magnetic Nanocomposite Microspheres

Isoniazid(INH)has high selectivity and strong bacteriostasis and sterilization effect on tuberculosis bacillus,and its oral administration is convenient and cheap,so it is currently the first-line drug for clinical treatment of tuberculosis.However,INH itself has toxic and side effects,the treatment cycle is short,and long-term use will produce drug resistance.It is an important means to develop a new type of anti-tuberculosis preparation with magnetic target drug sustained release performance to solve the defects of traditional drug treatment.The way of action of magnetic targeted drug delivery is to selectively deliver the targeted drug INH to the targeted tissues under the action of external magnetic field,which can not only improve the efficacy of drugs,but also effectively reduce the toxic and side effects of INH on the normal tissues of the body.Therefore,in this paper,INH as the targeted drug and Fe3O4 as the magnetic material were selected,and the water-soluble hyperbranched polymer(HBPE-SA)was used as the carrier.Fe3O4/HBPE-SA/INH magnetic nanocomposite microspheres with magnetic targeting sustained release function were prepared by two methods:stepwise method and one-step method respectively,and their structures and properties were studied.The main research contents are as follows:(1)Preparation of HBPE-SA:HBPE was prepared from 2,2-dimethylolpropionic acid,trimethylolpropane and p-methylbenzenesulfonic acid.HBPE was grafted with SA to obtain HBPE-SA.The results showed that SA was grafted to the end of HBPE successfully,and the grafting rate was 50%.(2)Fe3O4/HBPE-SA/INH magnetic nanocomposite microspheres were prepared by step method:magnetic Fe3O4 was firstly prepared by chemical co-precipitation,and then a certain amount of Fe3O4 was dispersed in the HBPE-SA/INH reaction system to prepare Fe3O4/HBPE-SA/INH magnetic nanocomposite microspheres.The drug loading and encapsulation rate of the magnetic nanocomposite microspheres were 46.76%and 26.65%respectively.The swelling experiment shows that the drug is released by diffusion and dissolution.In vitro release experiments showed that the magnetic nanocomposite microspheres had certain sustained release properties and pH sensitivity.Cytotoxicity experiments showed that it was nontoxic to cells and had good biocompatibility.(3)Preparation of Fe3O4/HBPE-SA/INH magnetic nanocomposite microspheres by one-step method:firstly,the preparation conditions of Fe3O4/HBPE-SA/INH magnetic nanocomposite microspheres were optimized by orthogonal experiment.The magnetic nanocomposite microspheres prepared under the optimal conditions had a drug loading of 73.08%and an encapsulation rate of 69.69%,and were dispersed evenly.In vitro release experiments show that magnetic nanocomposite microspheres have certain slow-release properties.The swelling and swelling experiments showed that the drug was released by diffusion.Cytotoxicity experiments showed that magnetic nanocomposite microspheres were nontoxic to cells and had good biocompatibility.Therefore,the preparation of two magnetic nanocomposite microspheres in this paper has a certain prospect for the clinical development and application of the treatment of tuberculosis.