Kamei Noriyasu, Nielsen Ebbe Juel Bech, Khafagy El-Sayed, Takeda-Morishita Mariko
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Hyogo, Japan.
Ther Deliv. 2013 Mar;4(3):315-26. doi: 10.4155/tde.12.164.
Insulin, a potent therapeutic peptide used in the treatment of diabetes, is administered to patients via subcutaneous injections because of the poor pharmacokinetics associated with alternative routes of administration such as oral, nasal and pulmonary delivery. Noninvasive nasal and oral formulations are appealing to patients who need consecutive daily treatments of insulin. However, to achieve mucosal absorption of insulin via oral or nasal administration, two barriers must be overcome: the impermeability of insulin through the epithelial membranes and local digestion and enzymatic degradation. Cell-penetrating peptides (CPPs), which efficiently bring exogenous proteins and nucleic acids into cells, have great potential to facilitate insulin permeation from the intestinal lumen or nasal cavity into systemic circulation via efficient uptake by epithelial cells. In fact, the coadministration of insulin with the peptide penetratin, a typical CPP, increased intestinal and nasal insulin bioavailability to 35 and 50%, respectively. In this review, the authors describe recent findings using this novel CPP-based formulation for noninvasive delivery of insulin.
胰岛素是一种用于治疗糖尿病的强效治疗性肽，由于其口服、鼻腔和肺部给药等替代给药途径存在不良药代动力学问题，所以通过皮下注射给患者用药。无创鼻腔和口服制剂对需要连续每日接受胰岛素治疗的患者具有吸引力。然而，要通过口服或鼻腔给药实现胰岛素的黏膜吸收，必须克服两个障碍：胰岛素透过上皮膜的不透性以及局部消化和酶降解。细胞穿透肽（CPPs）能有效地将外源蛋白质和核酸带入细胞，通过上皮细胞的有效摄取，有很大潜力促进胰岛素从肠腔或鼻腔渗透到体循环中。事实上，胰岛素与典型的CPP——穿膜肽共同给药，可分别将肠道和鼻腔胰岛素的生物利用度提高到35%和50%。在这篇综述中，作者描述了使用这种基于新型CPP的制剂进行胰岛素无创给药的最新研究结果。
