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首页> 外文期刊>Biomaterials >The targeting of surface modified silica nanoparticles to inflamed tissue in experimental colitis.
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The targeting of surface modified silica nanoparticles to inflamed tissue in experimental colitis.

机译：将表面改性的二氧化硅纳米颗粒靶向实验性结肠炎中的发炎组织。

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One aspect in the emerging field of nanomedicine is site specific drug delivery via nanoparticles. The use of nanoparticles allows for increased therapeutic efficiency with a lowered risk for and extent of adverse reactions resulting from systemic drug absorption. 5-Amino salicylic acid (5ASA) loaded silica nanoparticles (SiNP) are proposed here as drug delivery system for specific accumulation in inflamed colonic tissues allowing for selective medication delivery to such inflammation sites. The drug was covalently bound to SiNP by a four-step reaction process. In-vitro toxicity of modified SiNP was tested in appropriate cell culture systems, while targeting index and therapeutic efficiency were evaluated in a pre-existing colitis in mice. Particle diameter was around 140 nm after final surface modification. In-vitro drug release demonstrated significant drug retention inside the NP formulation. Toxicity of the different formulations was evaluated in-vitro cell culture exhibiting a lowered toxicity for5ASA when bound to SiNP. In-vivo, oral SiNP were found to accumulate selectively in the inflamed tissues allowing for significant amounts of drug load. SiNP demonstrated their therapeutic potential by significantly lowering the therapeutically necessary drug dose when evaluating clinical activity score and myeloperoxidase activity (untreated control: 28.0+/-5.0 U/mg; 5ASA-solution (100mg/kg): 8.2+/-3.4 U/mg 5ASA-SiNP (25mg/kg): 5.2+/-2.4 U/mg). SiNP allow to combine advantages from selective drug targeting and prodrugs appearing to be a promising therapeutic approach for clinical testing in the therapy of inflammatory bowel disease.
机译：纳米医学新兴领域的一个方面是经由纳米颗粒的定点药物递送。纳米颗粒的使用可以提高治疗效率，同时降低由于全身性药物吸收而引起的不良反应的风险和程度。在此提出了5-氨基水杨酸（5ASA）负载的二氧化硅纳米颗粒（SiNP），作为在发炎的结肠组织中特异性积聚的药物输送系统，允许选择性地将药物输送到此类炎症部位。该药物通过四步反应过程与SiNP共价结合。在适当的细胞培养系统中测试了修饰的SiNP的体外毒性，同时在小鼠中预先存在的结肠炎中评估了靶向指数和治疗效率。最终表面改性后，粒径约为140 nm。体外药物释放证明在NP制剂内部有明显的药物保留。在体外细胞培养中评估了不同制剂的毒性，当与SiNP结合时，其对5ASA的毒性降低。在体内，发现口服SiNP在发炎的组织中选择性积聚，从而使大量的药物负荷。当评估临床活性评分和髓过氧化物酶活性时，SiNP通过显着降低治疗上必需的药物剂量来证明其治疗潜力（未经处理的对照：28.0 +/- 5.0 U / mg; 5ASA溶液（100mg / kg）：8.2 +/- 3.4 U /毫克5ASA-SiNP（25毫克/千克）：5.2 +/- 2.4 U /毫克）。 SiNP可以将选择性药物靶向的优势与前药结合起来，前药似乎是炎症性肠病治疗中临床测试的有前途的治疗方法。

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