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Chinese Journal of Antituberculosis ›› 2013, Vol. 35 ›› Issue (5): 309-313.

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Preparation and evaluation of  poly(lactic-co-glycolic acid)/β-tricalcium phosphate/isoniazid slow-release material in animal model

LI Da-wei, MA Yuan-zheng, YANG Fei, CUI Xu, LI Li-tao, AN Jin-yu, ZHANG Jia-li   

  1. Orthopaedics Center, the 309th Hospital of People’s Liberation Army, Beijing 100091, China
  • Received:2013-02-22 Online:2013-05-10 Published:2013-07-02
  • Contact: MA Yuan-zheng E-mail:myzzxq@sina.com

Abstract: Objective To prepare poly(lactic-co-glycolic acid)/β-tricalcium phosphate material loaded with isoniazid and to evaluate its function in vitro and in vivo. Methods The lactic acid/glycolic acid copolymer was dissolved in 1,4-dioxane mixed with β-tricalcium phosphate and isoniazid powder to prepare a liquid slurry. The liquid slurry was mixed well-distributed under ultrasound, and then was put into a cylindrical artificial bone carrier to form the artificial bone materials. The morphology of the material was observed by electron microscopy scanning and the pharmacokinetics was analyzed with HPLC. Thirty-six New Zealand rabbits made femora condyle defects model were divided randomly into three groups(12 rabbits in each group). Group Ⅰ: loaded in active artificial bone without isoniazid. Group Ⅱ: loaded in active artificial bone with isoniazid. Group Ⅲ: non-loaded any materials as blank control. The repair of bone defects were observed and evaluated by imaging, histological scoring, bone growth rate after 4,8 and 12 weeks of operation. Results The artificial material can release INH constantly for 12 weeks. At the 12th week, all bone defects in the experimental groups(groupⅠand group Ⅱ) were radiographically repaired. The histological scoring and bone growth rate were 7.3±0.6,7.1±0.8,2.0±0.4 and 83.0%±7.0%, 84.0%±6.0%, 10.0%±1.1% in three groups, respectively. There were significant differences between groupⅠand group Ⅲ, also in group Ⅱ and group Ⅲ among histological scoring and bone growth rate(t values of histological scoring were 14.700,11.404,P<0.01. t values of bone growth rate were 20.604 and 24.262, P<0.01). But the parameters were similar in groupⅠand group Ⅱ(t values of histological scoring were 0.400,P>0.05. t values of bone growth rate -0.217, P>0.05). Conclusion Poly(lactic-co-glycolicacid)/β-tricalcium phosphate/isoniazid slow-release material can effectively repair bone defects in rabbits, its degradation rate well matches the bone formation rate and maintains INH release.

Key words: Isoniazid, Drug delivery systems, Polyglycolic acid, Lactic acid, Calcium phosphates, Tuberculosis, spinal