Development of non-invasive delivery of biopharmaceuticals equipped with novel membrane permeation technology and their translational research

本研究的目的是基于新的递送工具：细胞穿透肽（CPP）建立生物药物的非侵入性递送系统并进行转化研究，并获得以下结果：1）阐明CPP促进膜渗透作用的主要机理，2）新的肽序列通过使用人工神经网络的计算机探索性研究，获得了优于天然CPP的上级的PenetraMax，3）通过体内毒性试验阐明CPP的全身和局部高安全性。此外，为CPP临床制剂的开发提供了有用的知识，并基于上述结果，建立了进行口服PET成像研究的实验条件。

The purpose of this study was to establish non-invasive delivery systems for biodrugs based on new delivery tool: cell-penetrating peptides (CPPs) and to perform translational research, and the following results were obtained: 1) Elucidation of main mechanism of membrane permeation enhancing effects by CPPs, 2) Novel peptide sequence (PenetraMax) that is superior to natural CPPs was obtained by in silico exploratory research using an artificial neural network, 3) Clarification of CPPs' high safety systemically and locally by in vivo toxicity tests. Furthermore, useful knowledge for development of the clinical formulations of CPPs, and based on the above results, an experimental conditions to perform oral PET imaging studies were established.