中国组织工程研究 ›› 2022, Vol. 26 ›› Issue (34): 5475-5481.doi: 10.12307/2022.458

• 复合支架材料 composite scaffold materials • 上一篇    下一篇

装载黄芩苷锰基金属有机骨架材料的制备及体外释放

林令琪1,陈  进1,钱  昆2,赵  亮1,史一杰1   

  1. 1锦州医科大学药学院,辽宁省锦州市  121001;2锦州医科大学公共基础学院,辽宁省锦州市  121001
  • 收稿日期:2021-06-16 接受日期:2021-08-04 出版日期:2022-12-08 发布日期:2022-04-15
  • 通讯作者: 史一杰,博士,副教授,锦州医科大学药学院,辽宁省锦州市 121001
  • 作者简介:林令琪,男,1997年生,山东省临沂市人,汉族,锦州医科大学药学院在读硕士,主要从事药物新剂型研究。
  • 基金资助:
    辽宁省教育厅课题(JYTJCZR2020067),项目负责人:赵亮

Preparation and in vitro release of manganese-based metal-organic framework materials loaded with baicalin

Lin Lingqi1, Chen Jin1, Qian Kun2, Zhao Liang1, Shi Yijie1   

  1. 1School of Pharmacy, Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China; 2School of Public Basic Science, Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China
  • Received:2021-06-16 Accepted:2021-08-04 Online:2022-12-08 Published:2022-04-15
  • Contact: Shi Yijie, MD, Associate professor, School of Pharmacy, Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China
  • About author:Lin Lingqi, Master candidate, School of Pharmacy, Jinzhou Medical University, Jinzhou 121001, Liaoning Province, China
  • Supported by:
    Project of Liaoning Provincial Department of Education, No. JYTJCZR2020067 (to ZL)

摘要:

文题释义:
金属有机骨架:是由无机金属离子或团簇与有机配体组装形成的结晶性多孔材料,由于具有比表面积高、孔径可调、药物固载率高和生物可降解的优点,其在气体储存和分离、催化、生物传感和药物载体领域显示出广阔的发展前景。
药物pH响应释放:在生物医学应用中,如果药物能在特定的位置和时间以可控的方式得到释放,这种释药方式是理想的,但不同的器官和组织具有不同的pH值,这使得pH值成为药物可控释放的良好响应,药物实现pH值响应释放能够产生更好的治疗效果。

背景:近年来金属有机骨架材料被广泛应用于药物载体领域,其核心金属离子普遍以铁离子、钴离子、铜离子、锌离子为主,但对基于同等重要的锰离子的金属有机骨架研究还存在很大空缺。
目的:制备锰基金属有机骨架材料作为药物载体装载抗肿瘤药物黄芩苷,并研究其体外释药行为。
方法:通过水热搅拌法合成锰基金属有机骨架[Mn3(μ3-ade)2(OA)2]作为药物载体装载抗肿瘤药物黄芩苷,在装载药物前后分别通过X射线粉末衍射、红外光谱、扫描电镜、X射线光电子能谱对样品的结构、形貌、粒径进行表征分析,并考察锰基金属有机骨架的载药释药性能。
结果与结论:①当结晶时间为15 h时,合成样品的衍射峰位置、晶化度和衍射峰强度最佳;锰基金属有机骨架在pH=5.8的条件下更稳定;②装载药物后,锰基金属有机骨架的晶体结构发生明显变化,证实药物装载成功,在载体与药物质量比为1∶1、装载时间为8 h的条件下,载药率可高达(43.12±1.93)%;③体外释放实验结果表明,载药锰基金属有机骨架在pH值为5.8模拟肿瘤微环境释放介质中的累计释放率为(71.84±5.96)%,在pH值为7.4模拟人体微环境释放介质中的累计释放率为(48.90±7.21)%;④结果显示,在药物装载过程中晶体结构和形态发生转化,实现对黄芩苷的成功装载,并能根据pH值响应控制药物释放,从而形成有效的药物递送系统。

https://orcid.org/0000-0002-0773-212X (林令琪) 

中国组织工程研究杂志出版内容重点:生物材料;骨生物材料口腔生物材料纳米材料缓释材料材料相容性;组织工程

关键词: 黄芩苷, 金属有机骨架, 抗肿瘤药物, 载药率, 药物缓释, 水热搅拌法, 药物递送, pH值响应释放

Abstract: BACKGROUND:  In recent years, metal-organic framework materials have been widely used in the field of drug carriers. The core metal ions are generally dominated by iron, cobalt, copper, and zinc ions, but there is still a big gap in the study of metal organic frameworks based on the equally important manganese ions. 
OBJECTIVE: To synthesize a manganese-based metal organic framework as a drug carrier to load the anti-tumor drug baicalin, and to study its in vitro release behavior. 
METHODS: The manganese-based metal organic framework [Mn3(μ3-ade)2(OA)2] synthesized by a hydrothermal stirring method was worked as a drug carrier and loaded the anti-tumor drug baicalin. Before and after loading the drug, the structure, morphology and particle size of the samples were analyzed by X-ray powder diffraction, infrared spectroscopy, scanning electron microscope, and X-ray photoelectron spectroscopy, and the drug-loading and drug release performance of manganese-based metal organic frameworks were investigated. 
RESULTS AND CONCLUSION: (1) When the crystallization time was 15 hours, the diffraction peak position, crystallinity and diffraction peak intensity of the synthesized sample were the best. Manganese-based metal organic framework was stable at pH=5.8. (2) After loading the drug, the crystal structure of the manganese-based metal organic framework changed significantly, confirming the successful loading of the drug. Under the conditions that the mass ratio of carrier to drug was 1:1 and the loading time was 8 hours, the drug loading rate was the largest, which could be up to (43.12±1.93)%. (3) The in vitro release test results showed that the cumulative release rate of [Mn3(μ3-ade)2(OA)2] in a release medium whose pH was 5.8 simulated the tumor microenvironment was (71.84±5.96)%. The cumulative release rate in a release medium whose pH was 7.4 simulated the human microenvironment was (48.90±7.21)%. (4) The results show that during the drug loading, the crystal structure and morphology are transformed to achieve the successful loading of baicalin, and the drug release can be controlled according to the pH response, thereby forming an effective drug delivery system.

Key words: baicalin, metal organic framework, antitumor drugs, drug loading rate, sustained drug release, hydrothermal stirring method, drug delivery, pH-responsive release

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