With the growing number of marketed biological drugs, the development of technological strategies for their oral systemic absorption, becomes increasingly important. The harsh gastrointestinal environment and low permeability of the intestinal epithelium, represent a huge challenge for their systemic delivery. Herein, bioinspired in the physiological insulin-Zn interaction, the design of orthogonal-shaped protein-biometal hybrid nanocrystals, further enveloped by a bilayer of functional biomaterials, is reported. The nanocrystals exhibited a size of 80 nm, a neutral surface charge and a high insulin loading. In vitro studies showed the capacity of the nanocomplexes to control the release of the associated insulin, while preserving its stability. In vivo evaluation showed sustained blood glucose reductions in both healthy and diabetic rats (up to 40 % and 80 %, respectively), while chronic immunotoxicity studies in mice indicated no toxicity effect. Preliminary efficacy studies in healthy awake pigs following oral capsule administration showed over 20 % absolute bioavailability.

中文翻译：

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仿生正交形状的蛋白质-生物金属纳米晶体可实现口服蛋白质吸收


随着上市生物药数量的增加，开发其口服全身吸收的技术策略变得越来越重要。恶劣的胃肠道环境和肠上皮的低通透性，对其全身递送构成了巨大挑战。在此，在生理胰岛素-Zn 相互作用的生物启发下，报道了正交形状的蛋白质-生物金属混合纳米晶体的设计，进一步被双层功能性生物材料包裹。纳米晶体的尺寸为 80 nm，具有中性表面电荷和高胰岛素负载量。体外研究表明，纳米复合物能够控制相关胰岛素的释放，同时保持其稳定性。体内评估显示，健康大鼠和糖尿病大鼠的血糖持续降低（分别高达 40% 和 80%），而小鼠的慢性免疫毒性研究表明没有毒性作用。口服胶囊后对健康清醒猪的初步疗效研究表明，绝对生物利用度超过 20%。