纳米载体
生物利用度
小猎犬
药理学
药代动力学
脂质体
药物输送
肽
口服
细胞穿透肽
医学
化学
药品
内科学
生物化学
有机化学
作者
Philipp Uhl,Gzona Bajraktari‐Sylejmani,Dominik Witzigmann,Cindy Bay,Stefan Zimmermann,Jürgen Burhenne,Johanna Weiß,Walter E. Haefeli,Max Sauter
标识
DOI:10.1002/adtp.202300021
摘要
Abstract Oral delivery of peptides is severely limited by their instability and poor absorption in the gastrointestinal tract. In contrast to coadministration strategies using medium‐chain fatty acids, which have recently gained regulatory approval with low oral bioavailabilities ≤ 1% (Rybelsus and Mycapssa), efforts to clinically implement delivery systems based on nanocarriers have not been successful to date. The approved drug‐delivery formulations show fairly accurate correlation between clinical results and nonrodent mammal bioavailability, including Beagle dogs for Rybelsus, indicating that Beagle dogs represent a translationally relevant model. Here, a nanocarrier formulation for the oral administration of peptide therapeutics is reported with systemic targets consisting of liposomes decorated with cyclic cell‐penetrating peptides, which significantly increase oral bioavailability in translationally relevant Beagle dogs. This nanocarrier formulation is optimized using the glycopeptide vancomycin, and results in a considerable oral bioavailability of 3.9%. Further, this nanocarrier system increases the oral bioavailability of the large linear peptide therapeutic exenatide 20‐fold, and consistently achieves effective plasma concentrations in Beagle dogs.
科研通智能强力驱动
Strongly Powered by AbleSci AI