Oral delivery of liraglutide-loaded Poly-N-(2-hydroxypropyl) methacrylamide/chitosan nanoparticles: Preparation, characterization, and pharmacokinetics

The delivery of peptides or protein drugs via the oral route has always presented a significant challenge. Here, nanoparticles for the oral delivery of liraglutide are prepared. The nanoparticles are composed of the biodegradable carrier materials chitosan and poly-N-(2-hydroxypropyl) methacrylamide (pHPMA). In addition, CSKSSDYQC (CSK) and hemagglutinin-2 (HA(2)) are introduced into the particles to improve thein vivobioavailability of liraglutide. The size of the nanoparticles is less than 200 nm, and the encapsulation efficiency is approximately 80%. Compared with the subcutaneously injected liraglutide solution group (100%), the relative bioavailability of the nanoparticle group modified with CSK and HA(2)reached 10.12%, which is 2.53 times that of the oral liraglutide solution group.In vivoimaging results showed that pHPMA/HA(2)-CSK chitosan nanoparticles (pHPMA/HA-CCNPs) are retained in the gastrointestinal tract for up to 12 h, which is beneficial for oral absorption. CSK and HA(2)modified pHPMA/chitosan nanoparticles significantly improved liraglutide oral bioavailability and therefore have the potential to be applied for oral administration of peptides and proteins.

Automated summary

Delivery of peptides or protein drugs via oral route is challenging, but nanoparticles containing chitosan and pHPMA have shown potential for improving the bioavailability of liraglutide. By introducing CSK and HA(2) into the particles, the oral bioavailability of liraglutide can be significantly enhanced, making them a promising option for oral administration of peptides and proteins.