Semi-elastic core-shell nanoparticles enhanced the oral bioavailability of peptide drugs

We pioneered the semi-elastic core-shell nanoparticles as the carriers of the oral peptide drug and investigate the potential of enhancing the oral bioavailability of peptide drugs. These results in vitro cellular uptake and in vivo pharmacokinetic experiments demonstrated that the semi-elastic core-shell poly(lactic-co-glycolic acid) (PLGA)-lipid nanoparticles (LNPs) would be an excellent oral peptide delivery system for enhancing oral peptide bioavailability and worthy of further investigation as a promising candidate for oral disease treatment. [Display omitted] The rigidity of nanoparticles was newly reported to influence their oral delivery. Semi-elastic nanoparticles can enhance the penetration in mucus and uptake by epithelial cells. However, it is still challenging and unclear that the semi-elastic core-shell nanoparticles can enhance the oral bioavailability of peptide drugs. This study was for the first time to validate the semi-elastic core-shell poly(lactic-co-glycolic acid) (PLGA)-lipid nanoparticles (LNPs) as the carrier of the oral peptide drug. The antihypertensive peptide Val-Leu-Pro-Val-Pro (VP5) loaded LNPs (VP5-LNPs) were prepared by a modified thin-film ultrasonic dispersion method. Uptake experiment was performed in Caco-2 and HT-29 cells and monitored by high content screening (HCS) and flow cytometric (FCM). Pharmacokinetics of VP5-LNPs was carried out in Sprague-Dawley (SD) rats and analyzed by DAS 2.0. The optimal VP5-LNPs had an average particle size of 247.3±3.8nm, zeta potential of −6.57±0.45mV and excellent entrapment efficiency (EE) of 89.88%±1.23%. Transmission electron microscope (TEM) and Differential scanning calorimeter (DSC) further confirmed the core-shell structure. VP5-LNPs could increase the cellular uptake in vitro and have a 2.55-fold increase in AUC0-72h, indicating a great promotion of the oral bioavailability. The semi-elastic LNPs remarkably improved the oral availability of peptide and could be a promising oral peptide delivery system for peptide drugs in the future.