Until today, the oral delivery of peptide drugs is hampered due to their instability in the gastrointestinal tract and low mucosal penetration. To overcome these hurdles, PLA (polylactide acid)-nanoparticles were coated with a cyclic, polyarginine-rich, cell penetrating peptide (cyclic R9-CPP). These surface-modified nanoparticles showed a size and polydispersity index comparable to standard PLA-nanoparticles. The zeta potential showed a significant increase indicating successful CPP-coupling to the surface of the nanoparticles. Cryo-EM micrographs confirmed the appropriate size and morphology of the modified nanoparticles. A high encapsulation efficiency of liraglutide could be achieved. In vitro tests using Caco-2 cells showed high viability indicating the tolerability of this novel formulation. A strongly enhanced mucosal binding and penetration was demonstrated by a Caco-2 binding and uptake assay. In Wistar rats, the novel nanoparticles showed a substantial, 4.5-fold increase in the oral bioavailability of liraglutide revealing great potential for the oral delivery of peptide drugs.

中文翻译：

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PLA纳米颗粒用富含精氨酸的环状细胞穿透肽包被可口服递送利拉鲁肽。

直到今天，由于它们在胃肠道中的不稳定性和低的粘膜渗透性，阻碍了肽药物的口服递送。为了克服这些障碍，PLA（聚丙二酸）纳米颗粒被环状富聚精氨酸的细胞穿透肽（环状R9-CPP）包覆。这些表面改性的纳米粒子显示出与标准PLA纳米粒子相当的尺寸和多分散指数。ζ电势显示出显着的增加，表明成功的CPP偶联至纳米颗粒的表面。Cryo-EM显微照片证实了改性纳米颗粒的适当大小和形态。可以实现利拉鲁肽的高包封率。使用Caco-2细胞的体外测试显示出较高的生存能力，表明该新型制剂具有耐受性。通过Caco-2结合和摄取测定法证明了粘膜结合和渗透的强烈增强。在Wistar大鼠中，新型纳米颗粒在利拉鲁肽的口服生物利用度上显示出实质性的4.5倍增加，显示了肽药物口服给药的巨大潜力。