Study On Solubilization And Antitumor Activity Of Andrographolide By PEG-maleated Rosin Copolymer/Starch Compound System

Natural pharmaceutical ingredients such as andrographolide are usually found in solid crystal form.Which possess low water solubility and low bioavailability.How to improve the bioavailability of insoluble drugs has become a hot topic.Non-toxic and harmless natural materials are widely used in the field of bioengineering materials.In this study,Amphiphilic polymer micelles were successfully prepared and compounded with starch to solubilize andrographolide,which can greatly improve the bioavailability of andrographolide,and this new material giant has high biological safety,excellent slow-release effect and anti-cancer effect.The main contents and research process are as follows:Natural forest chemicals,maleic rosin,contain carboxylic acid groups and can be copolymerized with polyethylene glycol(PEG)to form amphiphilic polymaleic rosin polyethylene glycol ester(PRPE).PRPE was prepared into micelles by dialysis and loaded with andrographolide(AnG)successfully.The physical and chemical properties of PRPE are characterized by various instruments.The critical micelle concentration,particle size and potential of PRPE were measured.The morphology of AnG-PRPE micelles and the difference of drug loading under different preparation conditions were characterized.Finally,the release effect of AnG-PRPE in vitro was studied,and it was found that it has good sustained release effect.The cumulative release rate of AnG-PRPE in PBS buffer solution after 36 h was 64.03%,which was far less than the cumulative release rate of andrographolide technical drug within 24 h,86.93%,and the initial burst release was not observed.Corn starch(CS)and high amylose starch(HAS)were used as carriers to load andrographolide.The corn starch-andrographolide inclusion complex(CS-AnG)and high amylose starch-andrographolide inclusion complex(HAS-AnG)were prepared by ethanol method.The physicochemical properties and iodine complexing ability of the two inclusion complexes were characterized,and the anti-amylase hydrolysis ability and antioxidant activity in vitro of the inclusion complexes were determined.The release experiment in vitro showed that the inclusion complex had protective effect on the release of AnG under acidic conditions,and greatly delayed the release process of AnG in PBS solution.A new type of HAS-AnG-PRPE composite solubilization system was constructed by electrospinning with the combination of AnG-PRPE and HAS.It is found that the surface of the composite fiber membrane is smooth,without beading,and the diameter is 3-8 μm.It has good biocompatibility and no cytotoxicity.The release behavior of the composite fiber in vitro was studied.It was found that the composite fiber membrane had no obvious release behavior in hydrochloric acid buffer solution,and the cumulative release amount reached 83.13% in PBS buffer solution after 82 h,which had obvious sustained-release effect.The inhibitory effect of the composite fiber membrane on HepG2 cells was studied,and it was verified that the composite fiber membrane had good anti-hepatoma effect.