The dynamic assembly structure of insulin in oral nanoencapsulations studied by SANS

The oral delivery of insulin in diabetes treatment can improve patient compliance and avoidance of peripheral hyperinsulinemia. The mainbarriers faced by oral insulin are degradation by low pH and proteolytic enzymes in the gastrointestinal tract. The construction of oral insulin delivery systems need to be designed to keep insulin in stable hexamer assembly system in physiological environment. This project is focused on understanding the structure and dynamic assembly of insulin in different environments with or without protection of nanoencapsulations. Due to the difference of scattering length densities (SLD) of neutron between insulin and nanoencapsulations, we aim to establish an integrative structural and dynamical in situ characterizing platform by combining various neutron scattering techniques. Small angle neutron scattering (SANS) combined with contrast match strategy was used to characterize the structure of insulin in solution and in nanoencapsulations, and to investigate the dynamic assembly structure of insulin with or without nanoencapsulations in response to different environment.

糖尿病治疗中胰岛素的口服递送可提高患者依从性，并避免外周高胰岛素血症（peripheral hyperinsulinemia）。口服胰岛素面临的主要障碍是胃肠道中低pH值和蛋白水解酶（proteolytic enzymes）导致的降解。口服胰岛素递送系统的构建需设计为在生理环境中使胰岛素维持稳定的六聚体组装体系（hexamer assembly system）。本项目旨在探究胰岛素在有无纳米封装（nanoencapsulations）保护的不同环境中的结构与动态组装过程。由于胰岛素与纳米封装（nanoencapsulations）之间的中子散射长度密度（scattering length densities, SLD）存在差异，我们拟通过结合多种中子散射技术，建立一体化的原位结构与动态表征平台。小角中子散射（Small angle neutron scattering, SANS）结合对比度匹配策略（contrast match strategy）被用于表征溶液中及纳米封装（nanoencapsulations）内胰岛素的结构，并探究有无纳米封装（nanoencapsulations）保护时胰岛素响应不同环境的动态组装结构。