评估细胞穿透肽作为多功能、有效的吸收增强剂：与分子量和内在上皮药物通透性的关系。
Evaluation of Cell-Penetrating Peptides as Versatile, Effective Absorption Enhancers: Relation to Molecular Weight and Inherent Epithelial Drug Permeability.
机构信息
Laboratory of Drug Delivery Systems, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, Hyogo, 650-8586, Japan.
出版信息
Pharm Res. 2020 Sep 4;37(10):182. doi: 10.1007/s11095-020-02874-0.
PURPOSE
The poor permeability of new drug candidates across intestinal epithelial membranes complicates their development in oral form. This study investigated the potential of cell-penetrating peptides (CPPs) to improve the intestinal permeation and absorption of low-permeable low-molecular-weight (low-MW) drugs.
METHODS
The in vitro epithelial permeation of six different drugs (metformin, risedronate, zanamivir, methotrexate [MTX], tacrolimus, and vincristine [VCR]) across Caco-2 cell monolayers was examined in the presence and absence of L- or D-penetratin, and the correlation between permeation enhancement efficiency and the properties of tested drugs was analyzed. In addition, a rat closed ileal loop absorption study was conducted to determine the in vivo effects of penetratin.
RESULTS
MTX and VCR efficiently permeated Caco-2 monolayers in the presence of L- and D-penetratin, suggesting that CPPs enhanced the epithelial permeation of drugs with relatively high molecular weight and resultant limited intrinsic permeability. The in vivo rat closed ileal loop absorption study revealed the stimulatory effect of L- and D-penetratin on the intestinal absorption of MTX and VCR.
CONCLUSIONS
CPPs are useful as oral absorption enhancers for low-permeable drugs.
目的
新候选药物在肠上皮膜中的通透性差，这使得它们以口服形式开发变得复杂。本研究探讨了细胞穿透肽（CPPs）提高低通透性低分子量（低 MW）药物的肠道渗透性和吸收的潜力。
方法
在存在和不存在 L-或 D-穿透肽的情况下，研究了六种不同药物（二甲双胍、利塞膦酸钠、扎那米韦、甲氨蝶呤[MTX]、他克莫司和长春新碱[VCR]）在 Caco-2 细胞单层中的体外上皮渗透性，并分析了渗透增强效率与测试药物性质之间的相关性。此外，还进行了大鼠封闭回肠吸收研究，以确定穿透肽的体内作用。
结果
在 L-和 D-穿透肽的存在下，MTX 和 VCR 有效地渗透 Caco-2 单层，这表明 CPPs 增强了具有相对高分子量和固有渗透性有限的药物的上皮渗透性。体内大鼠封闭回肠吸收研究表明，L-和 D-穿透肽对 MTX 和 VCR 的肠道吸收具有刺激作用。
结论
CPP 可作为低通透性药物的口服吸收增强剂。
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