Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
Int J Pharm. 2010 Mar 30;388(1-2):209-12. doi: 10.1016/j.ijpharm.2009.12.060. Epub 2010 Jan 8.
We investigated the relationship between intermolecular binding and the ability of novel cell-penetrating peptides (CPPs) to enhance the nasal absorption of therapeutic peptides and proteins. The absorption-enhancing effect of a novel l-penetratin analogue, 'shuffle (R,K fix) 2' coadministered with different biotherapeutic peptides was evaluated after nasal administration in rats. Shuffle (R,K fix) 2 significantly increased the nasal absorption of insulin, glucagon-like-peptide-1 (GLP-1) and exendin-4, compared with the absorption seen with l-penetratin. Intermolecular binding was analyzed by surface plasmon resonance (SPR)-based binding assay. The binding characteristics implied that the higher the amount of CPP bound, the greater the nasal drug absorption. In addition, the calculated binding ratio between CPP and drug proved a critical aspect in enhancing the absorption of insulin and GLP-1. This difference in the enhancing effect of CPPs on nasal drug absorption is attributed to the degree of binding with the therapeutic macromolecule.
我们研究了分子间结合与新型细胞穿透肽（CPPs）增强治疗性肽和蛋白质经鼻吸收能力之间的关系。在大鼠体内经鼻给予不同生物治疗肽时，评估了新型 l-穿透肽类似物“shuffle（R，K fix）2”与不同生物治疗肽联合应用的吸收增强作用。与 l-穿透肽相比，shuffle（R，K fix）2 显著增加了胰岛素、胰高血糖素样肽-1（GLP-1）和 exendin-4 的经鼻吸收。通过表面等离子体共振（SPR）结合测定分析了分子间结合。结合特性表明，与 CPP 结合的量越高，鼻内药物吸收就越大。此外，计算得出的 CPP 与药物的结合比被证明是增强胰岛素和 GLP-1 吸收的关键方面。CPP 对鼻内药物吸收的增强作用的差异归因于与治疗性大分子的结合程度。
