Study On Preparation And Drug Release Of Smart Polymer Of Formononetin With PH/Redox Dual Response

Formononetin is a isoflavone compounds,which is mainly derived from the legume red clover.Because it has a dihydroxy phenol structure which is similar to animal estrogen.The higher dose of formononetin has an estrogen-like effect in the body,which can improve women's menopause to a certain extent.Further studies at home and abroad have found that formononetin has the equivalent effects of anti-oxidation,anti-atherosclerosis,prevention of osteoporosis,and inhibition of breast cancer and lung cancer cells.However,its significant shortcomings are low solubility,high permeability and low bioavailability,so researchers have been actively developing new formononetin preparations to give full play to its pharmacological effects.This paper combines molecular imprinting technology to synthesize a formononetin molecularly imprinted polymer(MIP)with a p H/redox dual response by reverse atom radical polymerization as a drug sustained release carrier.The experimental results show that the material has high drug loading capacity and better controlled release performance,and has a stimulus response to acid-base and redox conditions,.Therefore,it was expected to be used in intelligent drug delivery systems in the future.The specific research contents are as follows:(1)With reference to relevant literatures and the basis of research by the research group,the optimal synthesis conditions for formononetin smart drug carrier are obtained:formononetin(0.100 mmol),methanol(20.000 m L),MAA(0.400 mmol),formononetin(0.100 mmol),methanol(20.000 m L),MAA(0.400 mol),EGDMA(2.000 mmol),N,N'-bisacryloylcystamine(0.500 mmol),AIBN(60 mg),Cu Br₂(10 mg),PMDETA(20.1 u L),Fe₃O₄@Dextran carrier 100 mg.(2)Using multiple characterization methods to determine the structure,functional group composition and external morphology of the prepared smart response carrier MIP.The characterization results of FTIR,XRD and TEM showed that Fe₃O₄@Dextran surface was successfully grafted with formononetin molecularly imprinted layer,and the core-shell molecular imprinting material was successfully synthesized;the analysis results of TGA and VSM showed that the synthesized imprinting material has good properties of thermal stability and magnetic responsiveness,can use external magnetic field to quickly achieve separation.(3)The optimal adsorption conditions of the imprinting material are finally determined by solid-liquid ratio experiment,static adsorption and dynamic adsorption experiment.The ratio of adsorbent to adsorption medium is 3/5(W/V,mg·m L^-1),and the initial adsorption concentration is0.200.mg·m L^-1.Under these conditions,the adsorption of the imprinting material to the template molecule reaches the maximum value of 31.170mg·g^-1,and the adsorption time lasts 420 min.The results of selective experiments show that the imprinting factor of MIP was 7.898,indicating that the material has a specific recognition effect on formononetin.After six adsorption-desorption tests,the amount of MIP adsorbed on the template molecule is reduced from 31.170 mg·g^-1to 27.167 mg·g^-1,which is only 12.84%lower than the initial adsorption,indicating that the imprinting material has a considerable repetition.According to Scatchard analysis,the imprinting material may have two different adsorption sites for template molecules,high-affinity sites and low-affinity sites,while non-imprinting materials have only one binding method for formononetin;The results of kinetic adsorption experiments show that the adsorption process is more in line with the quasi-second-order kinetic model,indicating that the chemical mechanism may control the adsorption process.(4)Stimulus responsiveness.MIP is placed in six different release medias(PBS 4.0,PBS 4.0+10 mmol/l GSH,PBS 7.4,PBS 7.4+10mmol/l GSH,PBS 8.2,PBS 8.2+10 mmol/l GSH)for medicine.The results show that the cumulative release rate of the drug is proportional to the p H value,and the release rates under the conditions of p H 4.0,7.4,and 8.2 are 9.63%,10.07%,and 12.95%,respectively.However,after adding GSH,the cumulative release amount under the three p H values increases,which is 13.44%,42.43%,and 47.56%respectively.It can be seen that MIP has both p H and redox stimulus responses to the release of formononetin.