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

Improving the dissolution rate of water-insoluble diflunisal by γ-cyclodextrin metal-organic framework

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-organicframework, 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、N_2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。

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 ofcrystal growth. The poorly water-soluble diflunisal(DIF) was selected as the model drug and loaded into theinterior of porous CD-MOF by the impregnation method. The DIF loaded CD-MOF(DIF-MOF) was characterizedby 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 solubilizingcapability of CD-MOF were investigated. It revealed that the obtained CD-MOF was cubic-like with a narrow sizedistribution and high porosity. Negligible cytotoxicity was found after incubation with RAW264.7 cells. Comparedwith the pure CD-MOF carrier, the morphology and crystal form of DIF-MOF was not damaged during the drugloading process. Moreover, the solubility and release rate of water-insoluble DIF from the DIF-MOF were signifi-cantly increased.