Dual-drug sustained-release carrier:Preparation and performance / 中国组织工程研究

ABSTRACT

BACKGROUND: During conventional treatment for bone tuberculosis, there is a low effective concentration of anti-tuberculosis drugs, and the therapeutic effect is poor. OBJECTIVE:To develop a new biomaterial as a slow-release artificial carrier that can be directly implanted into the surrounding tissue of bone tuberculosis, maintain a certain anti-tuberculosis drug concentration for a long time, thereby playing an effective therapeutic action. METHODS:Rifampicin/polylactic acid/glycolic acid microspheres and isoniazid/polylactic acid/glycolic acid microspheres were prepared using the emulsion-solvent evaporation method. Usingα-cyanoacrylate, a biological adhesive, two kinds of microspheres were processed into a long-term slow-release bicomponent drug carrier. Then, in vitro release characteristics of the dual-drug sustained-release carrier were observed. After that, the dual-drug sustained-release carrier was implanted into rabbit intertrochanteric femur bone defects for observing drug release concentrations, histocompatibility and bone defect healing at different time points after drug delivery carrier implantation. RESULTS AND CONCLUSION:For rifampicin/polylactic acid/glycolic acid microspheres, the mean particle size was (240±13)μm, and the drug loading load rate was (26±1.5)%. For isoniazid/polylactic acid/glycolic acid microspheres, the mean particle size was (250±10)μm, and drug loading rate was (28±1.8)%. The in vitro cumulative release rate could reach 80%for rifampicin and 90%for isoniazid at day 90. The in vivo released concentration of rifampicin and isoniazid within 90 days was (0.5±0.4) and (0.6±0.3)μg/g, respectively. There were a smal amount of infiltrated neutrophils between the fascia and muscle fibers after the drug delivery carrier was implanted, and the amount of neutrophils in the muscle were reduced significantly at day 59. X-ray plain film showed that bone defects decreased obviously in size. These findings indicate that this dual-drug sustained-release carrier can maintain a certain anti-tuberculosis drug concentration in the surrounding tissues of bone tuberculosis, which is expected to provide a new type of dual-drug delivery carrier in the surgical treatment of bone tuberculosis.