Role of nanoparticle size, shape and surface chemistry in oral drug delivery.
Role of nanoparticle size, shape and surface chemistry in oral drug delivery.
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DOI：
10.1016/j.jconrel.2016.07.051
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发表时间：
2016-09-28
期刊：
影响因子：
--
通讯作者：
Mitragotri S
中科院分区：
文献类型：
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作者：
Banerjee A;Qi J;Gogoi R;Wong J;Mitragotri S
纳米颗粒在口服药物递送中发现了有趣的应用，因为它们呈现出与胃肠道相互作用的大表面积，并且可以以各种方式进行修饰以解决与口服递送相关的障碍。纳米颗粒的大小、形状和表面化学性质可以极大地影响细胞摄取和治疗效果。然而，颗粒尺寸、形状和表面化学之间的相互作用尚未得到很好的研究，特别是对于口服药物递送。为此，我们制备了球形，棒状和圆盘形纳米颗粒，并将其与靶向配体结合，以研究尺寸，形状和表面化学对其在肠道细胞中摄取和转运的影响。利用肠细胞的三重共培养模型来更接近地模拟肠上皮。结果表明，无论是否存在活性靶向部分，与球体相比，共培养物中杆状纳米颗粒的细胞摄取更高。纳米棒在肠道共培养物中的转运也显著高于球体。研究结果表明，纳米颗粒介导的口服药物递送可以潜在地改善偏离传统上用于纳米颗粒设计的球形形状。我们相信，了解纳米颗粒的几何形状在肠道吸收和运输的作用，将带来一个范式的转变，在纳米颗粒工程的口服递送和非球形纳米颗粒应进一步研究和考虑口服递送的治疗药物和诊断材料。
Nanoparticles find intriguing applications in oral drug delivery since they present a large surface area for interactions with the gastrointestinal tract and can be modified in various ways to address the barriers associated with oral delivery. The size, shape and surface chemistry of nanoparticles can greatly impact cellular uptake and efficacy of the treatment. However, the interplay between particle size, shape and surface chemistry has not been well investigated especially for oral drug delivery. To this end, we prepared sphere-, rod- and disc-shaped nanoparticles and conjugated them with targeting ligands to study the influence of size, shape and surface chemistry on their uptake and transport across intestinal cells. A triple co-culture model of intestinal cells was utilized to more closely mimic the intestinal epithelium. Results demonstrated higher cellular uptake of rod-shaped nanoparticles in the co-culture compared to spheres regardless of the presence of active targeting moieties. Transport of nanorods across the intestinal co-culture was also significantly higher than spheres. The findings indicate that nanoparticle-mediated oral drug delivery can be potentially improved with departure from spherical shape which has been traditionally utilized for the design of nanoparticles. We believe that understanding the role of nanoparticle geometry in intestinal uptake and transport will bring forth a paradigm shift in nanoparticle engineering for oral delivery and non-spherical nanoparticles should be further investigated and considered for oral delivery of therapeutic drugs and diagnostic materials.