THE DUAL-DRUG CARRYING ABILITY AND OSTEOGENIC EFFECT OF MESOPOROUS Fe3O4 NANOPARTICLES UNDER EXTERNAL MAGNETIC FIELD

Abstract

Bone tuberculosis is the most common extrapulmonary tuberculosis with a high incidence. Systemic administration of bone tuberculosis leads to the toxicity of liver and kidney. There are also problems of recurrence and bone defect after tuberculosis surgery. Therefore, construct a drug delivery system which can release anti-tuberculous substance continuously and promote the healing of bone defects have great significance. However, the load of single drug is often ineffective, and easy to produce drug resistance and affect the efficacy. In order to solve the difficulty of drug resistance of mycobacterium tuberculosis and the repairing bone defect after tuberculosis surgery, hollow mesoporous Fe3O4 nanoparticles (HMFNs) which can continuously release dual anti-tuberculous drugs and promote the repair of bone tissue at the site of bone tuberculosis were synthesized by the one-pot hydrothermal method. In this study, HMFNs were prepared as carriers. The rifampicin was successfully injected into the cavity of the HMFNs by using supercritical carbon dioxide methods and isoniazid can be adsorbed on the mesoporous shell of HMFNs by using vacuum filling methods. In addition, HMFNs were combined with sinusoidal electromagnetic field (SEMF) to regulate osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and pre-osteoblasts MC3T3-E1 in an “empty” state. The hollow structure of HMFNs has high magnetization saturation values ranging in 49.10–75.41 emu/g. HMFNs could co-encapsulate and co-deliver rifampicin and isoniazide drugs simultaneously. The in vitro release tests demonstrated extra sustained co-release profiles of rifampicin and isoniazide from HMFNs. HMFNs could promote the function of osteogenic differentiation in vitro with the help of external magnetic field stimulation, especially that with the intensities of 1 mT and 2 mT. HMFNs could be used as a magnetic targeting and dual sustained-release drug delivery system. HMFNs were combined with magnetic fields assisted