药学学报, 2019, 54(1): 29-35
引用本文:
吴碧湲, 周奕先, 潘昕, 权桂兰, 吴传斌. γ-环糊精金属有机骨架材料提高难溶性药物二氟尼柳的溶出速率[J]. 药学学报, 2019, 54(1): 29-35.
WU Bi-yuan, ZHOU Yi-xian, PAN Xin, QUAN Gui-lan, WU Chuan-bin. Improving the dissolution rate of water-insoluble diflunisal by γ-cyclodextrin metal-organic framework[J]. Acta Pharmaceutica Sinica, 2019, 54(1): 29-35.

γ-环糊精金属有机骨架材料提高难溶性药物二氟尼柳的溶出速率
吴碧湲, 周奕先, 潘昕, 权桂兰, 吴传斌
中山大学药学院, 广东 广州 510006
摘要:
本研究的目的是合成生物相容性优良的新型多孔材料γ-环糊精金属有机骨架(γ-cyclodextrin metal-organic framework,CD-MOF),并探究其作为药物载体改善难溶性药物体外释放行为。通过γ-环糊精与钾离子的分子自组装效应堆积形成骨架结构,并调控晶体的生长速率,得到不同粒径的CD-MOF。以难溶性药物二氟尼柳(diflunisal,DIF)为模型药物,利用浸渍法将药物装载至CD-MOF的孔道。采用扫描电镜、粉末X-射线衍射、N2吸附-解吸附、傅里叶红外光谱和热重分析等方法对不同尺寸多孔材料进行表征,并考察载体的细胞毒性和提高难溶性药物溶出速率的能力。实验结果表明,合成的CD-MOF呈孔道多样的立方体形貌、粒径均一、比表面积大和细胞毒性小。药物负载前后载体的形貌和晶型均未改变,难溶性药物二氟尼柳的溶解度和溶出速率显著提高。
关键词:    环糊精      金属有机骨架材料      溶解度      难溶性药物      二氟尼柳     
Improving the dissolution rate of water-insoluble diflunisal by γ-cyclodextrin metal-organic framework
WU Bi-yuan, ZHOU Yi-xian, PAN Xin, QUAN Gui-lan, WU Chuan-bin
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
Abstract:
The aim of this study is to prepare porous γ-cyclodextrin metal-organic framework (CD-MOF) with good biocompatibility to improve the in vitro release properties of water-insoluble drugs. Different sizes of CD-MOF were obtained by controlling the self-assembly of γ-cyclodextrin and potassium ion and the rate of crystal growth. The poorly water-soluble diflunisal (DIF) was selected as the model drug and loaded into the interior of porous CD-MOF by the impregnation method. The DIF loaded CD-MOF (DIF-MOF) was characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), nitrogen adsorption and desorption, Fourier infrared spectrometer and thermogravimetric analysis. In addition, in vitro cytotoxicity and solubilizing capability of CD-MOF were investigated. It revealed that the obtained CD-MOF was cubic-like with a narrow size distribution and high porosity. Negligible cytotoxicity was found after incubation with RAW264.7 cells. Compared with the pure CD-MOF carrier, the morphology and crystal form of DIF-MOF was not damaged during the drug loading process. Moreover, the solubility and release rate of water-insoluble DIF from the DIF-MOF were significantly increased.
Key words:    cyclodextrin    metal-organic framework    solubility    water-insoluble drug    diflunisal   
收稿日期: 2018-09-10
DOI: 10.16438/j.0513-4870.2018-0826
基金项目: 国家自然科学基金资助项目(81473155);广东省自然科学基金资助项目(2018A030310095).
通讯作者: 权桂兰,Tel:86-20-39943115,E-mail:quanglan@mail.sysu.edu.cn
Email: quanglan@mail.sysu.edu.cn
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