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

Abstract

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 (HA₂) are introduced into the particles to improve the <i>in vivo</i> bioavailability 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 HA₂ reached 10.12%, which is 2.53 times that of the oral liraglutide solution group. <i>In vivo</i> imaging results showed that pHPMA/HA₂-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 HA₂ modified pHPMA/chitosan nanoparticles significantly improved liraglutide oral bioavailability and therefore have the potential to be applied for oral administration of peptides and proteins.