Infection and Drug Resistance (May 2021)
Rifapentine Polylactic Acid Sustained-Release Microsphere Complex for Spinal Tuberculosis Therapy: Preparation, in vitro and in vivo Studies
Abstract
Zhen Wang,1,2,* Abulikemu Maimaitiaili,2 Tengfei Wang,2 Xinghua Song2,3,* 1Department of Orthopeadics, The Affiliated Linfen Hospital of Shanxi Medical University, Linfen, Shanxi Province, People’s Republic of China; 2Department of Orthopeadics, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People’s Republic of China; 3Department of Orthopeadics, The Affiliated Shunde Hospital of Jinan University, Foshan, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinghua SongDepartment of Orthopeadics, The Affiliated Shunde Hospital of Jinan University, Foshan, 528303, People’s Republic of ChinaEmail [email protected] WangDepartment of Orthopeadics, The Affiliated Linfen Hospital of Shanxi Medical University, Linfen, 041000, People’s Republic of ChinaEmail [email protected]: Spinal tuberculosis has been a common clinical extrapulmonary tuberculosis in recent years. The general anti-tuberculosis drug treatment cycle is long, with unsatisfactory efficacy. This study focused on the preparation and evaluation of rifapentine polylactic acid sustained-release microsphere complex for spinal tuberculosis therapy.Methods: Rifapentine polylactic acid sustained-release microspheres (RPSMs) were prepared through the double emulsion solvent evaporation method, and RPSMs were combined with hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) composite material to obtain drug-loaded, sustained-release complex. We evaluated the complex for dynamics of drug release and osteogenic ability using in vitro release test, alkaline phosphatase and alizarin red staining, real-time PCR and Western blot. A rabbit model of a spinal tuberculosis defect was established and repaired using HA/β-TCP or complex. The ability of anti-tuberculosis and tissue repair effects of the complex were evaluated through in vivo experiments.Results: The complex constructed of RPSMs and HA/β-TCP demonstrated a long drug release time, with no significant inhibition of cell osteogenic differentiation in vitro experiments. Postoperative macroscopic observation, immunohistochemical staining and Nilsson histological scores showed that the complex has good effects on the tissue repair. Moreover, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), important indexes of inflammation, decreased to normal levels in the complex group.Conclusion: In vitro and in vivo experiments demonstrated that the complex constructed of RPSMs and HA/β-TCP effectively treated spinal tuberculosis. Therefore, the complex represents a promising approach for the treatment of spinal tuberculosis.Keywords: spinal tuberculosis, sustained-release microsphere, antibiotics-loaded bone composite scaffold, rifapentine, tissue engineering
