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 in vivo 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. In vivo 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.

Reactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease

“…[263] Due to the drawbacks of conventional injectable insulin, nanomaterials carrying insulin for oral and pulmonary delivery have been developed. [264] In addition, anti-diabetic drugs, such as phytocompounds, [265] Metformin, [266] Dapagliflozin, [267] Empagliflozin, [268] Liraglutide, [269] Exenatide, [270] and Linagliptin [271] have been reported to use alginate, [272] chitosan, [272a,273] poly(lactic-co-glycolic acid) (PLGA), [274] dextran, [258,275] poly(alkyl cyanoacrylates) (PACA), lipid, [276] poly(lactic acid) (PLA), [277] micelle, [278] Niosome, [279] etc., as delivery systems. More strikingly, zinc oxide nanoparticle (ZnONP) itself has shown anti-diabetic effect.…”

Preparation and In Vitro and In Vivo Evaluation Of Panax Notoginseng Saponins-loaded Nanoparticles Coated with Trimethyl Chitosan Derivatives

“…To better penetrate the mucus network and epithelial cell membrane, the size of the nanoparticles needs to be controlled below 200 nm. 29,30 In this study, the size of the nanoparticles met this requirement. As shown in Fig.…”

New insights into nanomedicines for oral delivery of glucagon‐like peptide‐1 analogs

“…The NPs maintained a neutral surface charge before and after coating with pHPMA, which is ideal to avoid the interaction of the particles with mucins. The authors also showed the nanosystem had a 2.5‐times higher liraglutide AUC (~3284 pg.h/mL) and B R (~10%) values, than oral free liraglutide in solution (AUC ~1298 pg.h/mL and B R ~4%) in normoglycemic mice (Shi et al, 2021). B R was calculated according to Equation (1).…”