Study Of Interaction Between Polysaccharides And Drugs Based On Capillary Electrophoresis

Polysaccharides are indispensable biological macromolecules,which has potential as a drug carrier because of its structure and various biological activity characteristics.So it is of great significance to study the interaction between polysaccharide and drug interaction research is of great significance.Because capillary electrophoresis has the advantages of fast analysis speed and good accuracy,the solution system is close to the composition of biological solution,and it can get more realistic information such as intermolecular interaction.Therefore,the research method of polysaccharide and drug interaction is the most.In this study,the capillary electrophoresis peak drift method and ligand separation method were applied to the interaction between natural polysaccharide and antitumor drugs.And the binding constant was calculated by Scatchard equation,which provided theoretical data for the selection of molecular weight and the release site of natural polysaccharide.Related studies can provide the data on the degree of interaction between polysaccharides and drugs to evaluate the feasibility and efficacy of polysaccharides as drug carriers,which have clear research value and practical significance in the screening and evaluation of drug carriers.The main research works and results are as follows:1.The interaction between β-cyclodextrin and 5-fluorouracil was studied by capillary electrophoresis peak drift method.The interaction system of β-cyclodextrin and 5-fluorouracil was constructed.The electrophoretic peak drift model was used to test the electrophoretic graphs of the interaction between β-cyclodextrin and 5-fluorouracil at three different pH values.The binding constants were obtained by Scatchard calculation model.The results demonstrated that β-cyclodextrin and 5-fluorouracil had the strongest interaction under acidic conditions,and the binding constant was 232.5.Under alkaline conditions,the interaction was weak and the binding constant was 84.24.Under neutral conditions,almost no binding.In addition,the linear regression of the Scatchard equation is linearly good,indicating a binding of 1: 1 for both.2.The interaction between chitosan and 5-fluorouracil was studied by capillary electrophoresis peak drift method.The interaction system of chitosan and 5-fluorouracil was constructed.The electrophoresis graphs of the interaction between chitosan and 5-fluorouracil at different molecular weight concentrations were tested by capillary electrophoresis peak drift model The binding constants of two molecular weights were obtained by Scatchard calculation model.The results demonstrated that the binding constant of chitosan and 5-fluorouracil was 5.625 × 10~3,and the binding constant of chitooligosaccharide and 5-fluorouracil was 5.608 × 10~4.The binding constant of chitooligosaccharides and 5-fluorouracil is one order of magnitude higher than that of chitosan,indicating that the size of the interaction between chitosan and 5-fluorouracil of different molecular weights is different,Small molecular weight oligosaccharides are more likely to interact with chitosan.This is due to the large molecular weight of chitosan than the molecular weight of small chitooligosaccharides has greater steric hindrance.While the molecular weight of small chitooligosaccharides,there are more active modification sites,so chitooligosaccharides are more likely to bind to 5-fluorouracil than chitosan.In addition,the linear regression of the Scatchard equation is linearly good,indicating a binding of 1: 1 for both.3.The interaction between oligomeric hyaluronic acid and 5-fluorouracil and its derivatives was studied by capillary electrophoresis peak shift method and ligand separation method.The interaction system of oligomeric hyaluronic acid and 5-fluorouracil was constructed.The electrophoresis graphs of the interaction between oligo-hyaluronic acid and 5-fluorouracil and its derivatives were tested by capillary electrophoresis peak drift model.At the same time,the binding constants of oligomeric hyaluronic acid and 5-fluorouracil derivatives were calculated by capillary electrophoresis ligand separation method,the binding constants of the three cases were obtained by Scatchard calculation model.The results demonstrated that the binding constant of oligomeric hyaluronic acid and 5-fluorouracil under acidic conditions was 726.5,Under the alkaline condition was 672.3,Scatchard equation linear regression diagram is linear,indicating that the two are 1: 1 binding;Neutral conditions did not get a linear relationship,it was judged that the two are not binding under this condition.The interaction between the oligomeric hyaluronic acid tested with 5-fluorouracil derivatives and the linear regression mapping was poor,and it was judged that it might not be a 1: 1 binding,and the peak drift model was not suitable for further analysis.The binding constants of oligomeric hyaluronic acid and 5-fluorouracil derivatives were calculated by using the Capillary Electrophoresis Ligand Separation Method,and the Scatchard equation was used to test the electrophoretic graphs.The oligonuclear hyaluronic acid and 5-fluorouracil derivatives were 5.7847 × 10~7 and 1.3595 × 10~7 respectively.The binding of oligo hyaluronic acid and 5-fluorouracil derivatives in the case of chemical bonding is multi-site combination.4.The interaction between homozygous polysaccharide and 5-fluorouracil was studied by capillary electrophoresis peak shift method.The polysaccharides of all kinds(TFP、TFP1、TFP2、TFP3)were prepared by water extraction and alcohol precipitation.The antioxidant activities of these three groups were evaluated by DPPH method at the molecular level,three kinds of homologous polysaccharides were obtained by the purification of the strongest oxidative activity TFP2.The effect of 5-fluorouracil on the interaction between 5-fluorouracil and its derivatives was studied by using TFP2-2 with the highest urinary acid content of 20.16% and 5-fluorouracil as the research object.The electrophoretic graphs was obtained by capillary electrophoresis peak drift model,and the binding constant was obtained by Scatchard calculation model.The results demonstrated that the binding constant of TFP2-2 and 5-fluorouracil was 9.886 × 10~4,and the correlation coefficient was good,both of which were 1: 1.The binding constants indicated that TFP2-2 binds to 5-fluorouracil and belongs to fast binding type.TFP2-2 can be used as a drug carrier for further study.The related results of the study showed the feasibility of the plant polysaccharide as a carrier,at the same time,which provided criterion and and the related basic information for the comprehensive utilization of polysaccharides.