Developing oral biological therapeutics poses challenges because of their limited ability to penetrate cells and maintain stability in the gastrointestinal (GI) tract. This study aims to tackle these challenges by utilizing nanoscale materials and structures. The goal is to improve the oral delivery of biological therapeutics which could boost patient adherence to treatment and increase therapeutic effectiveness.
In this study, a stable oral nanoformulation was successfully developed using bile acid derivatives, and its endocytosis mechanism was elucidated. We first investigated the transport of bile acid derivatives via endocytosis simultaneously mediated via ASBT and EGFR. Both ASBT and EGFR are involved, leading to enhanced oral bioavailability and a glucose-lowering effect comparable to subcutaneous peptide therapeutics.
In this study, oral peptide therapeutics that utilize transporter-mediated endocytosis were developed, starting from an in silico design and progressing to in vitro/in vivo PK–pharmacodynamic efficacies. This strategy can be expanded and applied to other existing peptide therapeutics sequences with high efficacy and stability, helping to reduce the time and cost of drug discovery to the non-clinical stage.
The primary objective of this study was to determine an optimal MCT(metronomic chemotherapy) regimen for the orally available anticancer drug formulations, by establishing concentration-response relationships of tumor suppression effect and toxicity of anticancer drug.