加替沙星-聚癸二酸酐局部缓释系统的生物相容性

Biocompatibility of gatifloxacin-poly(sebacic anhydride) local control release system

背景:聚酸酐材料具有表面溶蚀性、生物可降解性和释药速率可调性,已被美国食品和药物管理局批准用于人体药物缓释材料。目的:研究加替沙星-聚癸二酸酐局部缓释系统的制备及生物相容性。方法:采用熔融缩聚的方法制备聚癸二酸酐,将加替沙星与聚癸二酸酐充分混合,制成载药量20%的加替沙星-聚癸二酸酐局部缓释药棒。切开6只新西兰大耳白兔背部皮肤,随机分组:实验组在脊柱两旁椎旁肌肌袋内植入聚癸二酸酐棒,对照组未植入任何材料。术后第5周取材,观察皮下组织和肌肉组织变化,以及心、肝、肾及肺的变化。结果与结论:聚癸二酸酐生物相容性良好,植入期间兔未出现任何食欲和行为改变,植入部位未见明显红肿、出血及糜烂,植入材料表面呈多孔状,表明材料在皮下已发生降解吸收,但未发生脆裂和崩解,与周围组织形成轻微粘连;兔肝、肾、肺、心组织结构未发生改变。表明加替沙星-聚癸二酸酐局部缓释制剂无毒、无致畸作用,组织相容性好。

BACKGROUND： Polyanhydride material is characteristics of surface erosion, biodegradability and release rate adjustability, and it has been approved by the U.S. Food and Drug Administration for human drug carrier materials. OBJECTIVE： To prepare gatifloxa-poly（sebacic anhydride） local control release system and study its biocompatibility. METHODS： Poly（sebacic anhydride） was prepared with melt phase polycondensation method, and mixed with gatifloxacin in the agate mortar to make a local drug delivery system at 20% drug loading. Six rabbits were used to study the biocompatibility of poly（sebacic anhydride） and their back skin was cut open. Six rabbits were randomly divided into two groups, the experimental group was implanted with poly（sebacic anhydride） stick into the paraspinal muscle pouch, while the control group received no implants. Rabbits were killed at 5 weeks post-surgery, and changes on subcutaneous tissue and muscle tissue were observed, as well heart, liver, kidney and lung. RESULTS AND CONCLUSION： Poly（sebacic anhydride） has a good biocompatibility. After implantation, no rabbit appeared to have the change of appetite and behavior. There was no edema, hemorrhage and erosion at the implanted site, and the surface of implanted materials was porous, which suggested that the materials had been degraded and absorbed subcutaneously. In addition, embrittlement and disintegration were not observed; the implanted materials slightly adhered to surrounding tissue. There was no change in the liver, kidney, lung, heart and partial musculature. Gatifloxacin-poly（sebacic anhydride） local sustained release preparation is well histocompatible with no toxicity and teratogenic action.