title: Isoniazid conjugated poly(lactide-co-glycolide): long-term controlled drug release and tissue regeneration for bone tuberculosis therapy.
abstract: Bone tuberculosis (TB) is one of the most common extrapulmonary TB. Effective integration of chemotherapy and bone regeneration is an optimal solution for bone TB therapy. Herein, we produce a composite scaffold drug delivery system fabricated with an isoniazid conjugated star poly(lactide-co-glycolide) (PLGA-INH4) and β-TCP. The cytological assay indicated the composite system possesses good biocompatibility. The in vitro and in vivo drug release evaluations showed that the composite system can intactly release the pristine INH and maintain effective INH concentration in a controlled manner for more than 100 days, and achieve high localized drug concentration and low systemic drug concentration. The rabbit radius repair experiment testified the scaffold has good bone regeneration capacity. Our work demonstrate the composite system can simultaneously achieve localized long-term drug controlled release and bone regeneration, which provides a promising route for improved bone TB treatment.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Da
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, The 309th Hospital of the PLA, Beijing 100094, China; Graduate School, Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The 309th Hospital of the PLA, Beijing 100094, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Wang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Baoxia
authors.initials: B
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, Anhui, China.
authors.forename: Yezi
authors.initials: Y
authors.lastname: You
authors.affiliation: Department of Orthopaedics, The 309th Hospital of the PLA, Beijing 100094, China; Graduate School, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address: myzzxq@sina.com.
authors.forename: Yuanzheng
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: fyang@iccas.ac.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: dcwu@iccas.ac.cn.
authors.forename: Decheng
authors.initials: D
authors.lastname: Wu
authors.affiliation: Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics & Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Shenguo
authors.initials: S
authors.lastname: Wang
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D006835:Hydrazones / Q000737:chemistry; D007538:Isoniazid / Q000737:chemistry*; D008297:Male; D051379:Mice; D011098:Polyglactin 910 / Q000737:chemistry*; D011817:Rabbits; D011884:Radius / Q000473:pathology; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D014394:Tuberculosis, Osteoarticular / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D006835:Hydrazones; D011098:Polyglactin 910; D007538:Isoniazid
keywords: Bone repair; Bone tuberculosis; Drug delivery; Isoniazid; Scaffolds