Fabrication of the anti-tuberculosis controlled drug delivery system with Ti-PDA-PEG-PLGA-INH and investigation of the biological characteristics
10.3760/cma.j.issn.0253-2352.2016.11.010
- VernacularTitle:钛表面聚多巴胺、聚乙二醇、聚乳酸-聚羟基乙酸、异烟肼抗结核控释涂层的构建及生物学性能
- Author:
Yunlong MA
;
Litao LI
;
Dan LI
;
Mingli PENG
;
Guanren ZHAO
;
Dawei LI
;
Zhanpeng LUO
;
Suxi GU
;
Fei YANG
;
Yuanzheng MA
- Publication Type:Journal Article
- Keywords:
Tuberculosis;
Isoniazid;
Ethylene glycol;
Delayed-action preparations
- From:
Chinese Journal of Orthopaedics
2016;36(11):725-734
- CountryChina
- Language:Chinese
-
Abstract:
Objective To fabricate an anti?tuberculosis controlled drug release coating with Ti?PDA?PEG?PLGA?INH and to investigate its surface characteristics, in vivo and in vitro drug release behavior, and tissue biocompatibility. Methods 4?arm?polyethylene glycol (PEG) was synthesized first. Then cover the surface of titanium (Ti) with a layer of poly dopamine (PDA) by Michael addition reaction. Use porous starch and 4?arm?PEG as a carrier, load with isoniazid (INH), then attach to the surface of titanium by casting or sol?gel dip coating methods, and then cover with a layer of poly lactic?co?glycolic acid (PLGA) by the same method, to fabricate the Ti?PDA?PEG?PLGA?INH composite coating finally. The functional group of 4?arm?PEG was charac?terized by proton nuclear resonance spectroscopy (HNMR). The surface characteristics of Ti?PDA?PEG?PLGA?INH were evaluated by scanning electron microscope (SEM), while drug release behaviors were detected by high performance liquid chromatography (HPLC) and the cumulative release rate was calculated, and carry out the antibacterial performance in vitro. The animal model of femoral condyle bone defect was established in 25 New Zealand white rabbits. Titanium rods covered with PDA?PEG?PLGA?INH coating were implanted into defect area. INH concentrations were detected by HPLC in venous blood, muscle and bone tissue at each time point postoperatively. Another 12 rabbits were randomly divided into experimental group and control group, the experi?mental group was implanted with titanium tablets and titanium rods coated with PDA?PEG?PLGA?INH in the paraspinous muscle and left femoral condyles respectively, while the control group was implanted with a blank sheet of titanium tablets and titanium rods in the same place. Hematoxylin and Eosin Staining were used to observe the biocompatibility of the composite system in vivo at 28 and 56 days postoperatively. Results Ti?PDA?PEG?PLGA?INH controlled drug release coating uniformly distributed on the surface of plates and rods, with translucent form and smooth surface. In vitro INH release kinetics exhibited a short?burst release during the first 8h, and the cumulative release of the INH was about 65%. On the 9th day, the cumulative release of the INH was about 90%, and then the release tended to be flat, and the drug release behavior in vitro continued more than 20d. In vivo release test showed that the concentration of INH in vein blood, muscle and bone tissue around the composite system was increased steadi?ly postoperatively. On about the 28th day, the concentration reached the max. However, the INH concentrations in muscle and bone tissue around the composite system were still higher than the minimum inhibitory concentration (MIC) on the 56th day. The antibacterial test in vitro showed that the titanium tablets coated with PDA?PEG?PLGA?INH formed obvious bacterial inhibition zones. The pathological results indicated that mild inflammatory reaction was seen in the 4th week postoperatively, and the reac?tive capsule formed with loose connective tissue. In the 8th week postoperatively, there's no obvious inflammation occurred, and the reactive capsule became more dense and thicker. Conclusion The study successfully fabricated the Ti?PDA?PEG?PLGA?INH anti?tuberculosis controlled drug release coating, with reasonable release behavior both in vivo and in vitro, effective antibac?terial effect of Mycobacterium tuberculosis in vitro and good tissue biocompatibility, which is a potentially effective drug delivery system for spinal tuberculosis.
