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Curcumin encapsulated zeolitic imidazolate frameworks as stimuli responsive drug delivery system and their interaction with biomimetic environment

机译:姜黄素包封的沸石咪唑酸酯骨架作为刺激响应药物递送系统及其与仿生环境的相互作用

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摘要

Metal organic frameworks (MOFs) exhibit unique features of finely tunable pore structures, excellent chemical stability and flexible surface structural functionality, making them advantageous for a wide range of applications including energy storage, compound separation, catalysis, and drug delivery. The present work enlightens a novel approach of single step fabrication of CCM-ZIF-8 as a drug carrier and its application as stimuli responsive drug delivery systems via external stimuli involving change in pH and in presence of biomimetic cell membrane like environment using liposomes and SDS micelles. The methodology is devoid of any post synthesis drug loading steps. The synthesized curcumin encapsulated ZIF-8 frameworks demonstrate ultrahigh drug encapsulation efficiency (ca. 83.33%) and good chemical stability. In vitro drug release of curcumin was three times higher in acidic medium than in physiological pH. Cytotoxicity results demonstrated enhanced therapeutic effect of CCM-ZIF-8 than free curcumin. Confocal microscopy results confirmed the easy cellular internalization of CCM-ZIF-8 in HeLa cells. Intracellular distribution studies at various incubation times confirmed the clathrin-mediated endocytosis to lysosomal pathway of CCM-ZIF-8, but without mitochondria being an intracellular fate. The results signify that CCM-ZIF-8 is an efficient drug carrier for passive tumor therapy in future for cancer treatments.
机译:金属有机骨架(MOF)表现出独特的特征,它们具有可微调的孔结构,出色的化学稳定性和灵活的表面结构功能,使其非常适合包括能量存储,化合物分离,催化和药物输送在内的广泛应用。本工作启发了一种新的方法,即一步制备CCM-ZIF-8作为药物载体,并通过涉及外部刺激的pH值变化和存在类似脂质体和SDS的仿生细胞膜样环境,将其用作刺激响应药物传递系统。胶束。该方法没有任何合成后药物装载步骤。合成的姜黄素封装的ZIF-8框架显示出超高的药物封装效率(约83.33%)和良好的化学稳定性。酸性介质中姜黄素的体外药物释放比生理pH高三倍。细胞毒性结果证明,CCM-ZIF-8比游离姜黄素具有更高的治疗效果。共聚焦显微镜结果证实了CCM-ZIF-8在HeLa细胞中易于细胞内在化。在不同孵育时间的细胞内分布研究证实了网格蛋白介导的CCM-ZIF-8溶酶体途径的内吞作用,但线粒体不是细胞内的命运。结果表明,CCM-ZIF-8是将来用于癌症治疗的被动肿瘤治疗的有效药物载体。

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