Study On The Preparation And Drug Release Of Hollow Magnetic Silybin (Liquid Crystal)Molecularly Imprinted Polymers

Silybin is the main active ingredient in milk thistle extract?Silymarin?of the compositae,which is a flavonolignan compound.Studies have shown that silybin haspharmacological effects include protecting and stabilizing hepatocyte membranes,protecting hepatocytes and their enzyme systems,promoting the repair and regeneration of hepatocyte membranes,removing reactive oxygen free radicals,resisting lipid peroxidation,and preventing fat from infiltrating the liver.Nowadays,silybin has become one of the most widely used drugs for the treatment of liver diseases.It is a clinically recognized drug for the treatment of liver injury.It can effectively treat liver diseases such as hepatitis,alcoholic or non-alcoholic fatty liver,early cirrhosis and various toxic liver injuries.However,the clinical therapeutic effect of traditional silybin agentswas discounted byits poor water solubility,poor lipid solubility and low bioavailability after oral administration.In addition,silybin has the characteristics of the rapid metabolism and frequent administration,which causes large fluctuations in blood concentration and poor compliance of patients.Therefore,the research to develop new dosage form of silybin both home and abroad are very actively,we used molecular imprinting technology,and innovatively introduced the hollow structure and liquid crystal into the imprinting system to prepare the hollow magnetic silybin liquid crystal molecular imprinted polymer?HMS@LC-MIP?and hollow magnetic silybin molecular imprint polymer?HMMIP?drug sustained-release materials.The experimental results show that HMS@LC-MIP greatly improves the drug loading of the imprinted material and the bioavailability of silybin,and achieves sustained release of silybin,which provides a potential theoretical reference for the application of liquid crystal molecularly imprinted polymer in the field of drug delivery.The specific contents and conclusions of this study are as follows:?1?The optimum condition for the preparation of HMMIP was determined by orthogonal experiments:silybin?0.05 mmol?,MAA?0.20mmol?,Acetonitrile?12.00 ml?,EGDMA?2.50 mmol?,CuBr₂?10.00 mg?,PMDETA?20.10?L?and hollow Fe₃O₄@mSiO₂-MPS?75.00 mg?.?2?Based on the orthogonal experimental results of HMMIP,the liquid crystal monomer as a crosslinking agent was used to replace part of EGDMA.The optimal condition for preparing HMS@LC-MIP was determined by single-factor experiments:silybin?0.05 mmol?,MAA?0.20 mmol?,Acetonitrile?5.00 ml?,Toluene?7.00 ml?,MPDE?2.00mmol?,EGDMA?0.50 mmol?,CuBr₂?10.00 mg?,PMDETA?20.10?L?and hollow Fe₃O₄@mSiO₂-MPS?75.00 mg?.?3?The structure,composition and morphology of the HMS@LC-MIP and HMMIP were studied by various characterization methods.FT-IR?XRD?VSM?TGA?TEM and BET showed that the surface of hollow Fe₃O₄@mSiO₂-MPS was wrapped with imprinted layer,and the imprinted materials have a hollow core-shell structure.HMS@LC-MIP and HMMIP particles could be quickly separated by a magnet,which indicated that the imprinted material had better magnetic responsivity.?4?Through solid-liquid ratio experiments,dynamic adsorption experiments,static adsorption experiments,selective adsorption experiments and reproducibility experiments to explore the adsorption performance of HMS@LC-MIP and HMMIP.The results of HMS@LC-MIP and HMMIP adsorption performance of silybin showed that the adsorption capacity is maximum when the amount of imprinted material is 5 mg,the silybin acetonitrile solution volume was 5 mL,and the concentration was 0.06 mg?mL^-1.The maximum adsorption amounts were 18.53 mg?g^-1,15.40 mg?g^-1,and theimprinting factors were 1.91 and1.89,respectively;The adsorption of silybin by HMS@LC-MIP and HMMIP reached equilibrium at 180 min and 240 min,respectively,while the traditional solid imprinted polymer required 7 h to reach equilibrium.It showed that the adsorption of silybin by liquid crystal matrix HMS@LC-MIP is a fast process with the advantages of faster mass transfer and binding kinetics;The Scatchard fitting curves of HMS@LC-MIP and HMMIP indicated there were two types of binding sites in the imprinted material,the high selectivity site with high binding energy and the low affinity site with low binding abilities;At the same time,the dynamic adsorption process was more suitable for the pseudo-second-order kinetic model,which proved that the adsorption process may be related to chemical action and may affect the adsorption rate;In selective adsorption experiments,HMS@LC-MIP exhibited better selectivity than HMMIP;After six cycles of experiments,the adsorption amounts of silibinin by HMS@LC-MIP and HMMIP were reduced by14.1%and 8.77%,respectively.The experimental results showed that the imprinted materials have good stability and reproducibility.?5?In vitro drug release experiment was designed to study the release behavior of HMS@LC-MIP and HMMIP.These results indicated the pH sensitivity of HMS@LC-MIP and HMMIP,and silybin release rate decreased with the decreasing pH values.In the simulated gastric juice?pH=2?,the sustained release time of HMS@LC-MIP and HMMIP attained 48 h and 36 h,respectively.HMS@LC-MIP showed excellent sustained-release properties.In addition,the release behavior of HMS@LC-MIP and HMMIP had a higher fitness with the Ritger-Peppas model,which indicated that the release mechanism of HMS@LC-MIP and HMMIP was non-Fickian diffusion.