Isoniazid-loaded chitosan/carbon nanotubes microspheres promote secondary wound healing of bone tuberculosis

Poor blood circulation makes it difficult for antitubercular drugs to achieve effective bactericidal concentration at tuberculose focus. The residual Mycobacterium tuberculosis around surgical wound would multiply, resulting in nonunion or sinus formation. Carbon nanotubes have strong tissue penetration and can cross many kinds of physiological barriers. Here, we constructed a chitosan/carbon nanotubes nanoparticles to control slow release of isoniazid. Transmission electron microscopy and nanoparticle tracking and analysis results showed that the diameter of chitosan/carbon nanotubes nanoparticles was between 150 and 250 nm. Chitosan/carbon nanotubes nanoparticles significantly prolonged the release time of isoniazid, and the release rate was more uniform, no sudden release was observed. In vitro experiments showed that chitosan/carbon nanotubes nanoparticles did not destroy biological function of isoniazid, but could reduce its cytotoxicity and inflammation. We further constructed animal model of tuberculous ulcer. The results showed that isoniazid/chitosan/carbon nanotubes nanoparticles promoted the healing of tuberculosis ulcer. Compared with isoniazid group and isoniazid/carbon nanotubes group, the area of wounds decreased by 94.6% and 89.8%, respectively. Immunohistochemistry showed that CD3+ and CD4+ T cell number decreased significantly in isoniazid/chitosan/carbon nanotubes group. In conclusion, we constructed a kind of isoniazid/chitosan/carbon nanotubes nanoparticles, which can significantly promote the healing of tuberculosis ulcer. Our study provided an effective way for the treatment of secondary wound healing of bone tuberculosis.