Transport and delivery of interferon- through epithelial tight junctions via pH-responsive poly(methacrylic acid-grafted-ethylene glycol) nanoparticles
Transport and delivery of interferon- through epithelial tight junctions via pH-responsive poly(methacrylic acid-grafted-ethylene glycol) nanoparticles
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DOI：
10.1080/1061186x.2018.1547732
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发表时间：
2019-07-03
影响因子：
4.5
通讯作者：
Peppas, Nicholas A.
中科院分区：
文献类型：
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作者：
Caldorera-Moore, Mary;Ramirez, Julia E. Vela;Peppas, Nicholas A.
虽然我们对癌症的基本理解已经取得了重大进展，但它们尚未转化为有效的临床癌症治疗方法。有可能提高癌症治疗效果的领域之一是开发新型药物递送技术。特别地，pH敏感性聚合物络合水凝胶的设计可以允许多种化疗药物和蛋白质的靶向口服递送。在这项工作中，聚（甲基丙烯酸接枝的乙二醇）水凝胶纳米粒子的合成，表征，并作为基质型，扩散控制，pH响应载体，使口服化疗药物干扰素α（IFN-）的研究。利用Caco-2/HT 29-MTX共培养物作为胃肠道模型，研究了控制IFN-γ转运的生物物理机制。合成的纳米颗粒表现出pH响应性溶胀行为，并允许IFN-γ通过发达的细胞GI上皮模型的紧密连接渗透。这些研究证明了这些颗粒有助于改善蛋白质化疗剂的口服递送的能力。
Whereas significant advancements have been made in our fundamental understanding of cancer, they have not yet translated into effective clinical cancer treatments. One of the areas that has the potential to improve the efficacy of cancer therapies is the development of novel drug delivery technologies. In particular, the design of pH-sensitive polymeric complexation hydrogels may allow for targeted oral delivery of a wide variety of chemotherapeutic drugs and proteins. In this work, poly(methacrylic acid-grafted-ethylene glycol) hydrogel nanoparticles were synthesised, characterised, and studied as matrix-type, diffusion-controlled, pH-responsive carriers to enable the oral delivery of the chemotherapeutic agent interferon alpha (IFN-). The biophysical mechanisms controlling the transport of IFN- were investigated using a Caco-2/HT29-MTX co-culture as a gastrointestinal (GI) tract model. The synthesised nanoparticles exhibited pH-responsive swelling behaviour and allowed the permeation of IFN- through the tight junctions of the developed cellular GI epithelium model. These studies demonstrate the capabilities of these particles to contribute to the improved oral delivery of protein chemotherapeutics.