title: Dopamine-assisted fixation of drug-loaded polymeric multilayers to osteoarticular implants for tuberculosis therapy.
abstract: Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular 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. dcwu@iccas.ac.cn fyang@iccas.ac.cn and University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The 309th Hospital of the PLA, Beijing 100094, China. myzzxq@sina.com.
authors.forename: Litao
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, The 309th Hospital of the PLA, Beijing 100094, China. myzzxq@sina.com.
authors.forename: Yunlong
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. dcwu@iccas.ac.cn fyang@iccas.ac.cn and University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: Department of Orthopaedics, The 309th Hospital of the PLA, Beijing 100094, China. myzzxq@sina.com.
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
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. dcwu@iccas.ac.cn fyang@iccas.ac.cn.
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. dcwu@iccas.ac.cn fyang@iccas.ac.cn.
authors.forename: Xing
authors.initials: X
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. dcwu@iccas.ac.cn fyang@iccas.ac.cn and University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, The 309th Hospital of the PLA, Beijing 100094, China. 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. dcwu@iccas.ac.cn fyang@iccas.ac.cn and University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Decheng
authors.identifier: http://orcid.org/0000-0002-5276-8607
authors.initials: D
authors.lastname: Wu
mesh_terms: D000269:Adhesives / Q000737:chemistry*; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005260:Female; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D007538:Isoniazid / Q000008:administration & dosage* / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D019736:Prostheses and Implants; D011817:Rabbits; D014394:Tuberculosis, Osteoarticular / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000269:Adhesives; D000995:Antitubercular Agents; D007211:Indoles; D011108:Polymers; C568283:polydopamine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D007538:Isoniazid