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 uncl...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 coreshell 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 monito red by high content screening(HCS)and flow cyto metric(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±3.8 nm,zeta potential of-6.57±0.45 mV 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 AUC0-72 h,indicating a great promotion of the o ral 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.展开更多
基金financially supported by the Science and Technology Project of Shenzhen(No.JCYJ20170413155047512)Scientific Research Foundation of the Science and Technology Department of Sichuan Province,China(No.2018JY0143)。
文摘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 coreshell 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 monito red by high content screening(HCS)and flow cyto metric(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±3.8 nm,zeta potential of-6.57±0.45 mV 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 AUC0-72 h,indicating a great promotion of the o ral 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.
