Research Of Biocmpatible Silybin Impeinted Materials Based On Dual PH/Temperature Response

Thistle is a plant of the genus Milk Thistle,which can extract a flavonoid lignan compound silymarin from the seed coat of its seeds and the main active ingredient is silybin.Silymarin is mainly composed of three isomers of silybin,silydianin,and silychristin,among which silybin has the highest content and the best activity.Studies have shown that silymarin can prevent liver damage caused by chemical toxins,food toxins and drugs,stabilize liver cell membrane,promote regeneration and repair of liver cells,antioxidants,etc.However,the traditional silybin treatment has lots of disadvantages such as large dose,long duration,and high toxic and side effects and so on.In this paper,a pH/temperature dual-response,biocompatible and degradable carrier was prepared by electron transfer activation regenerated catalyst atom transfer radical polymerization（ARGET ATRP）for loading and releasing silybin.In order to improve the bioavailability and reduce the dosage and side effects of drugs.The first chapter of the paper briefly describes the basic characteristics of silybin traits and molecularly imprinted polymers as drug carriers.The research background,significance,purpose,characteristics,innovation and technical route of this paper are also summarized.The second chapter of the paper described the experimental methods,contents,steps,instruments,reagents and materials used in this study in detail.The third chapter of the paper discussed and analyzed the experimental data and results.The details were as follows:（1）The optimum preparation conditions for the double-response MIP were obtained by reference to literature reports and laboratory studies:polymerization solvent ACN 10 mL,functional monomer MAA0.25 mmol,thermal response monomer NIPAm 0.25 mmol,crosslinker EGDMA 3 mmol,carrier Fe₃O₄@CS@APTES@BiBB 100 mg.The maximum adsorption capacity of MMIPs prepared under these optimized conditions was 5.18 mg g^-1,and the imprinting factor was 3.20.（2）The characteristic functional groups,material morphology,crystal form,magnetic properties,thermal stability and element types of the obtained imprinted materials were characterized by FT-IR,SEM,XRD,VSM,TGA,XPS and other characterization methods.（3）The optimum adsorption conditions,adsorption kinetics and thermodynamic models of MMIPs,swelling ratio and degradation rate were studied.The optimal adsorption conditions were obtained by single factor experiment:the solid-liquid ratio was 30/5(W/V,mg mL^-1),the initial concentration of silybin was 0.08 mg mL^-1,and the contact time was 540 min.The Scatchard model was empolyed to evaluate the adsorption performance of MMIPs.It could be inferred that there were two main binding sites on MMIPs:high/low affinity sites.The maximum apparent adsorption capacity Q_max and equilibrium dissociation constant were 3.59 mg g^-1,2.16 mg g^-1 and 0.0108 mg mL^-1,0.0693 mg mL^-1,respectively.Since the pseudo second-order kinetic model could better fit the experimental data,indicated that the MMIPs adsorption process of silybin could be better explained by the pseudo second-order model.Swelling rate measurement experiments show that the material has both small pores that maintain a certain rigid structure and large pores that increase the drug loading.After 12 days of degradation at different pH（1.0,7.4,8.2）,it was found that the remaining materials were 15.5%,35%and 24.5%respectively,indicating that the structure of the synthesized imprinted material was relatively stable.（4）The double-response MMIPs released the silybin in vitro at different pH（1.0,7.4,8.2）and temperature（37.5℃,43℃）.The cumulative release rate of MMIPs reached 29%,23%and 25%in the release medium with pH=1.0,7.4 and 8.2 at 37.5℃.However,when the temperature was increased to 43℃（pH=7.4）,the cumulative release rate reached 49%,indicated that MMIPs had a dual pH/temperature response to the release of silybin.The fourth chapter of the article summarizes the experimental results and conclusions of this paper,and prospects the future application of molecularly imprinted polymers in drug transport and controlled release.