Preparation Of Mesoporous Fe₃O₄ Nanoparticles-based Drug Delivery Systems And Its Osteogenic Effect Under External Magnetic Field

Bone tuberculosis is the most common extrapulmonary tuberculosis and itsincidence is high.In order to solve the refractory and drug-resistant of bone tuberculosis and the difficulty of repairing bone defects after tuberculosis surgery,a drug delivery system capable of continuously releasing anti-tuberculosis drugs at the site of bone tuberculosis and promoting bone tissue repair is prepared,which has significant research significance in the treatment of bone tuberculosis.In this study,hollow mesoporous Fe₃O₄ nanoparticles?HMFNs?with uniformpores,large pore volume and specific surface area,and excellent cell transport performance were prepared as carriers to co-load a hydrophobic drug rifampicin and a hydrophilic drug isoniazid simultaneously and sustained release of drugs with different properties to avoid drug resistance.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.It provided a new method for the repair of bone defect after bone tuberculosis surgery.The main research contents of this paper are as follows:1.HMFNs were prepared by one-step hydrothermal method and analyzed by XRD,SEM,TEM and N₂ adsorption-desorption analysis.The results showed that the obtained HMFNs had mesopores and hollow structure.The MTT experiment,lactate dehydrogenase leak test,hemolysis experiment and cell uptake experiments proved that the obtained HMFNs had many properties such as good cell compatibility,blood compatibility and cellular uptake.2.The use of supercritical carbon dioxide successfully injected the hydrophobic drug rifampicin into the cavity of the HMFNs,and its drug loading amount could reach to 18.25%.Hydrophilic drug isoniazid can be adsorbed on the mesoporous shell of HMFNs with a drug loading amount of 9.55%.The drug delivery system has the properities of certain sustained-release and magnetic response in vitro,which could be used as a magnetic targeting and dual sustained-release drug delivery system.3.In combination with sinusoidal electromagnetic fields,the function of HMFNs in regulating osteogenic differentiation of BMSCs and MC3T3-E1 cells was studied in vitro.Cell proliferation,ALP activity,cell mineralization,Western blotting,and real-time fluorescent quantitative PCR were used to prove that there was no obvious effect on cell proliferation,differentiation and mineralization when the HMFNs and external magnetic field stimulated BMSCs and MC3T3-E1 cells separately,but the HMFNs combined with external magnetic field can promote the proliferation,differentiation and mineralization of BMSCs and MC3T3-E1 cells.The results showed that 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.