The preparation of core/shell structured microsphere of multi first-line anti-tuberculosis drugs and evaluation of biological safety.

To introduce a modified method, namely coaxial electrohydrodynamic atomization for the fabrication of distinct core/shell structured microspheres of four first-line ant-tuberculosis drugs with different characteristics in hydrophilic properties in one single step. In group B, we prepared microspheres in which the core and the shell contain hydrophobic and hydrophilic drugs, respectively. In contrast, in group C, the opposite is prepared. The detection of encapsulation efficiency and in vitro release test were performed to confirm the feasibility of the drug-loaded core/shell structured microspheres. Moreover, cell culture experiments and animal experiments have been carried out to evaluate the biological safety of different microspheres in cell growth, cell viability, osteogenesis and migration of BMSCs in vitro and the bone fusion in a bone deficits model in SD rat. Meanwhile, the distribution of drugs and liver and kidney toxicity were monitored. The release patterns of the two groups are significantly different. The release of drugs from Group B microspheres is rather sequential, whereas group C microspheres release drugs in a parallel (co-release) manner. And various concentrations of carrier materials produces core/shell structured microspheres with different appearance. Moreover, the biological safety of core/shell structured microspheres was testified to be satisfactory. These findings present the advantages and possible application of this kind of multi-drug release system in treating skeletal tuberculosis. Moreover, the characteristic sequential release of multi-drugs can be controlled and adjusted based on treatment need and used in treating other disorders.