Preparation,Characterization And Pharmacokinetics Of Pueraria Polysaccharide Loaded Nanocomposites

Because of its safety,universality and resource application,the homologous Chinese medicinal materials have attracted much attention.Pueraria is the dry root of Kudzu,a leguminous plant,which is widely produced and rich in resources.Now there are a variety of medical and health food prepared with pueraria or its active ingredients as raw materials,such as wild pueraria tea,pueraria meal replacement powder,pueraria liver capsule,etc.As one of the main active components of pueraria,pueraria polysaccharide has pharmacological activities such as anti-inflammatory,antioxidant,antialcoholic and hepatotropic,hypoglycemic and lipid lowering.However,whether it can deliver insoluble drugs in the drug delivery system and improve the oral bioavailability of the model drug needs further study.In this study,glucan gel G50 column chromatography was used to isolate and purify Pueraria crude polysaccharide(PPC).water soluble Pueraria polysaccharide(PPS)was soluble and homogeneous.Two kinds of nanocomposites,PPC-CUR and PPs-CUR were prepared by using PPC and PPS as carriers loaded with Curcumin(CUR).Molecular docking method was used to simulate the interaction between molecules and predict the potential active protein expression sites.Then,the preparation prescription of the nanocomplex was optimized,the stability and basic properties of PPC-CUR and PPS-CUR were investigated,and the oral pharmacokinetic characteristics of the nanocomplex in rats were studied.The main research results are as follows:(1)Purification and structure identification of pueraria polysaccharide excipientsPPC was isolated and purified by glucan gel G50 chromatography,and water-soluble purified pueraria polysaccharide PPS was collected.Its strong water solubility and low molecular weight were related to the abundance of hydroxyl group.The properties of PPS are stable,and the protein content is low.The molecular weight range of PPS is about 8058 Da.Based on the characterization data,the repeated sequence of water-soluble pueraria polysaccharide PPS was β-D-glucose-1,3-α-dglucose-1,4-α-d-glucose-1,6-α-d-glucose.(2)Molecular simulation of the interaction between pueraria polysaccharide and curcuminAuto-dock software was used to establish the optimal conformation of the above PPS monosaccharide sequences,simulate the molecular interaction between the PPS monosaccharide sequences and the water-insoluble model drug CUR,and predict and analyze the potential NF-kb channel protein targets of the PPS-CUR complex with the help of H-dock.The results showed that the bond energy between PPS and CUR was4.9 kcal/mol,and they could spontaneously bond,and hydrogen bond was the main force of their interaction.The binding energy between PPS-CUR and the potential protein expression sites of NF-kb pathway was-332.82 kcal/mol,indicating stable binding between the two pathways.To provide a theoretical basis for pueraria polysaccharide loading CUR,indicating that pueraria polysaccharide is a potential new drug preparation excipient.(3)Preparation and characterization of pueraria polysaccharide containing curcumin nanocomplexUsing PPC and PPS as drug delivery carriers,two kinds of nanocomposites were prepared by reverse-solvent precipitation method,and their basic properties were characterized,and their physical and optical stability were investigated.The particle sizes of the two nanocomposites are uniformly distributed and electronegative,and the particle sizes of PPS-CUR are smaller than PPC-CUR.The microstructure results showed that the nanocomposites exhibited planar laminar structure,and the apparent solubility and stability of the CUR were significantly improved by PPC-CUR and PPS-CUR.Under direct UV irradiation,polysaccharide complex showed different degrees of protection for CUR.The results of infrared spectrum showed that the bonding between CUR and PPC and PPS was mainly caused by hydrogen bond,which is the main bonding force between polymer and phenolic compounds.In conclusion,the water solubility and stability of the CUR were improved significantly by loading puerariae polysaccharides,and the loading capacity of PPS was better than that of PPC.The basic properties of the nanocomposites were consistent with the results of molecular simulation.(4)Oral pharmacokinetics of pueraria polysaccharide containing curcumin nanocomplexAn LC-MS/MS detection method with good reproducibility,high sensitivity and specificity was established.Using SD rats as animal models,the oral pharmacokinetics of the two nanocomposites were evaluated by intragastric administration and compared with the oral pharmacokinetics of CUR with the same dose in rats.The results showed that AUC0-24,AUC0-∞,Tmax and Cmax were 1.40,1.58,1.33 and 1.28 times for PPC-CUR and 2.04,3.01,2.67 and 2.36 times for PPSCUR,respectively,compared with the CUR for intragastric administration.The relative bioavailability of PPC-CUR and PPS-CUR increased to 157.83% and301.04%,respectively.The results showed that the prepared nanocomposites improved the absorption degree and average resident time of CUR in vivo,the bioavailability of CUR was significantly improved,and the release of CUR was delayed.