Applicability and Limitations of Cell-Penetrating Peptides in Noncovalent Mucosal Drug or Carrier Delivery Systems
Applicability and Limitations of Cell-Penetrating Peptides in Noncovalent Mucosal Drug or Carrier Delivery Systems
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DOI：
10.1016/j.xphs.2015.11.010
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发表时间：
2016-02-01
影响因子：
3.8
通讯作者：
Takeda-Morishita, Mariko
中科院分区：
文献类型：
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作者：
Kamei, Noriyasu;Nielsen, Ebbe Juel Bech;Takeda-Morishita, Mariko
我们最近的研究表明，细胞穿透肽（CPPs）在非共价药物cpp方法中具有安全有效地改善肽和蛋白质药物肠道吸收的潜力。为了阐明这一策略的适用性和局限性，本研究考察了货物尺寸对cps吸收刺激效应的影响。本研究选择不同尺寸的亲水性大分子葡聚糖（4.4、10和70 kDa）和聚苯乙烯基纳米颗粒（20、100和200 nm）作为模型货物。在原位大鼠肠道吸收研究中，CPPs （octaarginine, Tat, penetratin，和PenetraMax）增加了右旋糖酐的肠道吸收，其效率根据右旋糖酐的分子大小而变化。在CPPs中，即使与最大的葡聚糖（70 kDa）共给药，d -穿透素也显示出增强作用。相比之下，Caco-2细胞摄取的体外研究表明，CPPs将纳米颗粒递送到上皮细胞的能力取决于其颗粒大小，并且与CPPs共孵育可以促进200纳米颗粒相对较差的内化。这些发现表明，使用非共价CPP方法，大分子和颗粒货物的固有摄取特性决定了其肠粘膜递送的有效性。(C) 2016美国药剂师协会(R)。Elsevier Inc.出版。版权所有。
Our recent studies show that cell-penetrating peptides (CPPs) have potential to improve the intestinal absorption of peptide and protein drugs safely and effectively when used in the noncovalent drug-CPP approach. To clarify the applicability and limitations of this strategy, the present study examined the effects of cargo size on the absorption-stimulatory effect of CPPs. Different sizes of hydrophilic macromolecular dextran (4.4, 10, and 70 kDa) and polystyrene-based nanoparticles (20, 100, and 200 nm) were chosen as the model cargos in this study. In an in situ rat intestinal absorption study, CPPs (octaarginine, Tat, penetratin, and PenetraMax) increased the intestinal absorption of dextran, and the efficiency varied according to the molecular size of dextran. Among the CPPs, D-penetratin showed an enhancing effect even when coadministered with the largest dextran (70 kDa). By contrast, an in vitro study of Caco-2 cell uptake showed that the ability of CPPs to deliver nanoparticles into epithelial cells was dependent on their particle size and that the relatively poor internalization of 200-nm nanoparticles could be facilitated by coincubation with CPPs. These findings suggest that the intrinsic uptake properties of macromolecules and particulate cargos determine the effectiveness of their intestinal mucosal delivery using the noncovalent CPP method. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.