阿司匹林缓释微球的制备及体外缓释效果评估

Preparation of aspirin sustained-release microsphere and its in vitro releasing property

目的:阿司匹林(acetylsalicylic acid,aspirin)作为经典非甾体抗炎药,已被证实具有抗炎、调节免疫和促矿化作用,但是如何实现长期缓释aspirin并实现促进骨再生仍有待研究。本研究拟构建微球缓释体系,实现aspirin药物长期稳定缓慢释放,从而实现更为理想的成骨效果。方法:(1)合成制备三种缓释微球支架:①单纯物理浸提法合成硅酸钙(calcium silicate,CaSiO3)负载aspirin微球(CaSiO3+aspirin),②水包油(oil/water,O/W)乳化法制备聚乳酸羟基乙酸(poly lactic-co-glycolic acid,PLGA)负载aspirin微球(PLGA+aspirin),③O/W乳化法制备PLGA复合CaSiO3负载aspirin微球(PLGA+CaSiO3+aspirin),并通过调整PLGA与CaSiO3的比例,得到材料的最佳形貌。(2)缓释效果评价:用分光光度计测第1、2、4、6、9、13、17、21、24、30、36、45天微球浸提液的aspirin浓度,计算微球的aspirin载药率,绘制三种缓释微球支架的aspirin累积释放曲线并评价其缓释效果。结果:(1)环境扫描电镜下观察,三种微球支架表面结构规整,粒径均匀,但PLGA+aspirin组微球存在少量团聚现象,CaSiO3+aspirin组部分微球破裂,PLGA+CaSiO3+aspirin组微球均匀分布于CaSiO3粉末上。(2)三组的载药率分别为(1.06±0.04)%、(7.05±0.06)%和(6.75±0.18)%。(3)95%药物缓释时间分别为3 d、24 d和36 d,PLGA+CaSiO3+aspirin微球支架释放时间显著长于其余两组,且释放速率更为稳定。结论:PLGA+CaSiO3+aspirin复合微球支架具有较理想的阿司匹林缓释效果,该复合微球有望成为理想的成骨材料。

Objective:It has been proven that acetylsalicylic acid(aspirin),as a kind of classical non-steroidal anti-inflammatory drug,not only has the effect of anti-inflammatory,but also has the function of immunity regulation and mineralization.However,it needs further investigation to study how to delay release of aspirin for a long time and enable to promote bone regeneration.Herein,we demonstrated that the long-term delayed release pattern of aspirin through the construction of microsphere scaffolds is promising to achieve the excellent bone regeneration.Methods:Here we synthesized three kinds of scaffolds as follows:(1)aspirin loaded calcium silicate(CaSiO3)microsphere(CaSiO3-aspirin)via simple immersion;(2)aspirin loaded polylactic-co-glycolic acid(PLGA)microsphere(PLGA-aspirin)via oil/water(O/W)emulsion;(3)aspirin loaded PLGA-CaSiO3 scaffold(PLGA-CaSiO3-aspirin)via O/W emulsion,optimal morphology and structure of PLGA-CaSiO3-aspirin scaffold was acquired through modulating the ratio between PLGA and CaSiO3.Furthermore,spectrophotometer was used to monitor the concentration of the extract of the three scaffolds for different releasing time,including 1,2,4,6,9,13,17,21,24,30,36,and 45 days,aspirin loading efficiency and its accumulation releasing curves were both achieved according to the concentration of aspirin.Their sustained release effects of aspirin were evaluated eventually.Results:Environmental scanning electron microscope(ESEM)results showed that the surface structure of the three kinds of scaffolds were smooth and had uniform size distribution.In addition,a small amount of PLGA-aspirin microspheres occurred to aggregation,while a small amount of CaSiO3-aspirin microspheres were broken.Moreover,the PLGA-aspirin microspheres in the PLGA-CaSiO3-aspirin scaffolds were uniformly adhered to the surface of CaSiO3 microspheres.The aspirin loadings of CaSiO3-aspirin,PLGA-aspirin,and PLGA-CaSiO3-aspirin were(1.06±0.04)%,(7.05±0.06)%,and(6.75±0.18)%,respectively.In addition,their corresponding time for releasing 95%of aspirin was 3,24,and 36 days,respectively.The releasing time of PLGA-CaSiO3-aspirin was longer than that of the others and the releasing rate was more stable.Conclusion:The microsphere scaffold of PLGA-CaSiO3-aspirin composites has excellent delayed-release effect on aspirin,which is promising for using as osteogenic materials.