Stimuli-responsive local drug molecule delivery to adhered cells in a 3D nanocomposite scaffold

Stimuli-responsive local drug molecule delivery to adhered cells in a 3D nanocomposite scaffold
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DOI:
10.1039/c9tb00591a
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发表时间:
2019-06-21
影响因子:
7
通讯作者:
Kehr, Nermin Seda
Kehr, Nermin Seda
中科院分区:
工程技术2区
文献类型:
--
作者:
Motealleh, Andisheh;De Marco, Rossella;Kehr, Nermin Seda

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能够提供受控和局部药物释放的药物输送系统是生物医学领域中非常重要的工具,因为它们可以在最需要药物的地方提供定点、持续和受控的药物释放,并且它们允许在身体其他部位显著降低药物的剂量,减少药物的潜在副作用。在这方面,我们描述了具有不同pH响应强度的PMO/海藻酸盐纳米复合材料(NC)支架,用于受控的局部药物输送应用。为了制备PMO/藻酸盐纳米支架,首先将PMO负载抗癌分子,然后用非生物聚合物或生物聚合物包裹PMO,然后将PMO嵌入藻酸盐网络。我们发现,由于纳米支架所有带电成分之间的静电相互作用的pH依赖程度不同,PMOS的药物释放受到环境pH和PMOS表面涂层的调节。NC支架的非生物聚合物涂层配方可用于将更高剂量的药物分子直接输送到细胞,而生物聚合物涂层系统有助于药物的缓慢和长期释放以及增强细胞粘附性。尽管如此,这两个系统都可以被利用,特别是将更大剂量的药物分子直接输送到癌细胞,而将更少的药物输送到健康细胞。
Drug delivery systems capable of providing controlled and localized drug release are a highly important tool in the biomedical field because they can provide site-specific, sustained, and controlled drug release at the place where the drug is most needed, and they allow for significantly lower doses of the drug at other parts of the body, reducing the drug's potential side effects. In this respect, we describe pH-responsive PMO/ alginate nanocomposite (NC) scaffolds with different pH-responsive strengths for controlled local drug delivery applications. To prepare the PMO/ alginate NC scaffolds, PMOs were first loaded with anti-cancer molecules and then coated with a non-biopolymer or a biopolymer, after which the PMOs were embedded into an alginate network. We found that drug release from the PMOs was regulated by the pH of the environment and the surface coating of the PMOs due to the different pHdependent levels of electrostatic interactions between all the charged components of the NC scaffolds. The non-biopolymer-coated formulation of the NC scaffold can be utilized to deliver higher dosages of drug molecules directly to cells, while the biopolymer-coated system is useful for slow and prolonged release of drugs and for enhanced cell adhesion. Nonetheless, both systems can be utilized, in particular, to deliver higher dosages of drug molecules directly to cancer cells while delivering less of the drug to healthy cells.