阿司匹林缓释微球的制备及体外缓释效果评估

doi:10.19723/j.issn.1671-167X.2019.05.019

北京大学学报（医学版） ›› 2019, Vol. 51 ›› Issue (5): 907-912. doi: 10.19723/j.issn.1671-167X.2019.05.019

阿司匹林缓释微球的制备及体外缓释效果评估

陈英¹,刘中宁¹,李波^2,^△(),姜婷^1,^△()

1. 北京大学口腔医学院·口腔医院,修复科　国家口腔疾病临床医学研究中心　口腔数字化医疗技术和材料国家工程实验室　口腔数字医学北京市重点实验室,北京　100081
2. 重庆科技学院纳微复合材料与器件重庆市重点实验室,重庆　401331

收稿日期:2017-09-28 出版日期:2019-10-18 发布日期:2019-10-24
通讯作者: 李波,姜婷 E-mail:15011229485@139.com;Leewave@126.com
基金资助:
国家自然科学基金青年项目(81400498);国家自然科学基金面上项目(81771045);重庆市基础与前沿研究计划(CSTC2016JCYJA0541);重庆市教委科学技术研究项目(KJ1601301)

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

Ying CHEN¹,Zhong-ning LIU¹,Bo LI^2,^△(),Ting JIANG^1,^△()

1. Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China
2. Chongqing Key Laboratory of Nano/Micro Composite Materials and Devices, Chongqing University of Science and Technology, Chongqing 401331, China

Received:2017-09-28 Online:2019-10-18 Published:2019-10-24
Contact: Bo LI,Ting JIANG E-mail:15011229485@139.com;Leewave@126.com
Supported by:
Supported by the Youth Program of National Natural Science Foundation of China(81400498);the General Program of National Natural Science Foundation of China(81771045);the Natural Science Key Foundation Project of Chongqing(CSTC2016JCYJA0541);and the Scientific and Technological Research Program of Chongqing Municipal Education Commission(KJ1601301)

摘要/Abstract

摘要：

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),③ O/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。

关键词: 阿司匹林, 缓释微球, 抗炎, 成骨

Abstract:

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.

Key words: Aspirin, Sustained-release microsphere, Anti-inflammatory, Osteogenesis

中图分类号:

R944

陈英,刘中宁,李波,姜婷. 阿司匹林缓释微球的制备及体外缓释效果评估[J]. 北京大学学报（医学版）, 2019, 51(5): 907-912.

Ying CHEN,Zhong-ning LIU,Bo LI,Ting JIANG. Preparation of aspirin sustained-release microsphere and its in vitro releasing[J]. Journal of Peking University(Health Sciences), 2019, 51(5): 907-912.

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Scaffold	Aspirin (w/v)	PLGA (w/v)	PVA (w/v)	CaSiO₃ (w/v)
CaSiO₃+aspirin	1%	0	0	10%
PLGA+aspirin	1%	10%	2%	0
PLGA+CaSiO₃+aspirin	1%	10%	2%	10%-20%

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

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