咖啡酸-壳聚糖自组装微粒对菊苣酸口服吸收与抗氧化活性的影响OA

[Objective]The self-assembled microparticles of caffeic acid-grafted chitosan loaded with chicoric acid(CFA-g-CS/CA)were employed to optimize the in vitro drug release characteristics,oral absorption,and antioxidant activity of chicoric acid(CA),providing a new strategy for its efficient delivery and oral application.[Method]Based on the free radical-mediated grafting copolymer of caffeic acid and chitosan(CFA-g-CS),CA was encapsulated in the copolymer to form self-assembled microparticles.The in vitro drug release behavior of CFA-g-CS/CA and CA was investigated,and a pharmacokinetic study was conducted in rats.The pharmacokinetic parameters of CFA-g-CS/CA and CA were statistically analyzed to evaluate the oral absorption effect.The in vitro antioxidant activities of CFA-g-CS/CA,CFA-g-CS,and CA were measured using nitrogen-centered radical(DPPH),ABTS radical scavenging capacity,and the total antioxidant capacity(T-AOC)assay kits.Additionally,in hydrogen peroxide(H2O2)-induced oxidative stress models using human colon adenocarcinoma cells(Caco-2)and porcine small intestinal epithelial cells(IPEC-J2),the effects of CFA-g-CS/CA self-assembled microparticles on cellular oxidative damage were evaluated through both protective and remedial intervention modes.The effects of CFA-g-CS/CA and CA on the activity of intracellular antioxidant enzymes were also compared.[Result]The CFA-g-CS/CA self-assembled microparticles were successfully synthesized with a particle size of 382.6 nm.The in vitro release results indicated that CFA-g-CS/CA achieved a more rapid and complete drug release compared to CA,with the release process being substantially completed within 90 min.Pharmacokinetic results showed that CFA-g-CS/CA reached a peak plasma concentration(Cmax)of 1 221.6 ng/mL,with the oral relative bioavailability of 192%.In vitro antioxidant results showed that CFA-g-CS/CA exhibited extremely significantly superior DPPH and ABTS free radical scavenging abilities as well as total antioxidant capacity compared to CA and CFA-g-CS(P<0.01).Cell experiments showed that CFA-g-CS/CA increased the survival rates of Caco-2 and IPEC-J2 cells under H2O2-induced oxidative stress.In the protection and alleviation of oxidative damage in Caco-2 cells,the median inhibition concentration(IC50)of CFA-g-CS/CA was 145.9 and 201.3 μmol/L,respectively,and in IPEC-J2 cells,it was 130.4 and 187.5 μmol/L,respectively.In the protection test,compared with CA group,the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in Caco-2 cells in CFA-g-CS/CA group significantly or extremely significantly increased(P<0.05 or P<0.01),and the activities of catalase(CAT)and GSH-Px in IPEC-J2 cells also significantly increased(P<0.05).In the alleviation effect test,compared with CA group,the activities of SOD,CAT,and GSH-Px in Caco-2 cells of CFA-g-CS/CA group were significantly increased(P<0.05),and the activity of SOD in IPEC-J2 cells was also significantly increased(P<0.05).[Conclusion]This study successfully synthesized CFA-g-CS/CA self-assembled microparticles,which could significantly improve the drug release behavior of CA,effectively enhance its oral bioavailability,and increase its in vitro antioxidant activity.This strategy provided an effective solution for addressing the challenges of oral application of CA and other poorly soluble natural active ingredients,playing a significant role in promoting the development of green feed additives and the healthy growth of livestock production.