PLGA Bifunctional Nanoparticles For Enhanced Oral Drug Delivery

Objection: The dual-functional nanoparticles(FA/BO-PLGA-NPs)loaded with docetaxel(DTX)were prepared,in which a novel targeting drug carrier(FA/BO-PEI)based on the PEI modified with folic acid(FA)and borneol(BO).The aim of this research was to to confirm the dual-functional nanoparticles could improve oral absorption of DTX,providing important theoretical and practical references for preparating oral anticancer-nanoparticles.Methods: FA-PEI/BO-PEI were synthesized and used to prepare the dual-functional nanoparticles by solvent evaporation method;its morphology and mean size were analyzed by dynamic light scattering(DLS)and transmission electron microscope(TEM);drug loading(DL%)and entrapment efficiency(EE%)were investigated by HPLC;drug release and stability behavior in vitro was studied by dialysis method;intestinal absorption study was confirmed by recording the accumulative amount of FA/BO-PLGA-NPs in 2 hours;pharmacokinetic study of FA/BO-PLGA-NPs;Caco-2 cells were applied to evaluate the cellular uptake of FA/BO-PLGA-NPs;irritation of FA/BO-PLGA-NPs to intestinal was also studied.Results: The nanocarrier of FA-PEI/BO-PEI was successfully synthesized,which was spherical and smoothy in morphology with the average size of(137.0±2.12)nm,zeta potential of(45.93±1.58)m V.Besides,the EE% and DL% of(DTX)FA/BO-PLGA-NPs were(80.30±1.77)% and(2.27±0.29)%,respectively.In vitro release studies showed that about 62.11% of DTX released from FA/BO-PLGA-NPs in the media of p H 7.4.In vitro intestinal absorption test showed that the amount of intestinal absorption of FA/BO-PLGA-NPs was 5.99 times of that of DTX.In vivo experiments showed that the oral bioavailability of FA/BO-PLGA-NPs was enhanced about 6.8-fold compared with DTX suspension.The result of cellular features in vitro showed that FA/BO-PLGA-NPs could significantly enhance cellular uptake.In vitro cell uptake assay showed that the uptake of FA/BO-PLGA-NPs by Caco-2 cells was significantly higher than that in the DTX group.When the proton inhibitor FCCP was added,the folate uptake is reduced.When Vd3 was incubated with Caco-2 cells,cell uptake of FA/BO-PLGA-NPs was the highest.Nanoparticles caused no obvious irritation indicating that FA/BO–PLGA-NPs exhibited a potential in oral drug delivery.Conclusion: FA/BO-PLGA-NPs were prepared successfully and could significantly enhance cellular uptake and improve intestinal absorption.The pharmacokinetic behavior of DTX was markedly improved by FA-PEI/BO-PEI with longer retention time and bigger AUC values.FA/BO-PLGA-NPs promoted cellular uptake by inhibiting function of P-gp and enhanced the active targeting property related to PCFT transporter.FA/BO-PLGA-NPs exhibited a potential in oral drug delivery.