The Study On Design And Application Of Hydrogel/Nanomaterial Drug Delivery System Based On Quercetin

Quercetin(3,3’,4’,5,7-pentahydroxyflavonoid)is the most common flavonoid and is widely found in vegetables and fruits.Quercetin has attracted extensive attention due to its excellent pharmacological functions such as antioxidant,anti-inflammatory,anticancer and neuroprotective.However,the poor water solubility,instability and rapid metabolism of quercetin also make its bioavailability low,so its clinical application is greatly limited.In order to better exert the pharmacological effect of quercetin,two drug delivery systems based on quercetin,dynamic covalent hydrogel and nanomicelle,were developed to improve the bioavailability of quercetin and make it have Potential ability to penetrate the blood-brain barrier to reach therapeutic targets.The specific research includes the following two parts:(1)A supramolecular hybrid hydrogel(CFQ hydrogel)was prepared by dynamic covalent cross-linking between carboxymethyl chitosan,2-formylphenylboronic acid,and quercetin using a simple synthetic method.gel).The gel formation mechanism of the hydrogel was studied by a series of analytical methods such as infrared spectroscopy,hydrogen NMR spectroscopy,and ultraviolet spectroscopy.The gel formation,microscopic morphology and mechanical properties of the hydrogel were studied.The hydrogel exhibited good self-healing,stability and injectability.In addition,the in vitro drug sustained release test showed that the CFQ hydrogel has a good drug sustained release effect,and the sustained release time can reach more than 14 days.The L929 cytotoxicity evaluation confirmed the good cytocompatibility of the CFQ hydrogel.The postoperative anti-adhesion ability of CFQ hydrogel was further evaluated in a rat model of cecal abrasion with lateral wall defect,and the tissue adhesion rate was significantly increased by increasing the quercetin concentration in the CFQ hydrogel-treated group compared with the control group Reduced,and the worn parts have also been well restored.The prepared composite gel exhibits excellent antibacterial,anti-inflammatory and antioxidant effects,and is an ideal anti-postoperative adhesion and wound treatment material.(2)A quercetin-based mitochondrial-targeted micelle(T-D/Que/PEG-PE micelles)was designed and synthesized,which has synergistic effects of inhibiting the aggregation of Aβ1-42 monomers and anti-oxidative stress,is expected to be a potential therapeutic candidate for the treatment of Alzheimer’s disease.The structure and morphology of the micelles were characterized by infrared spectroscopy,~1H NMR spectroscopy,transmission electron microscopy,particle size analyzer and other analytical methods.The potential is-13.50±3.44 m V.DPPH scavenging activity test shows that T-D/Que/PEG-PE micelles have antioxidant effect.Circular dichroism test results also indicated that micelles inhibited the aggregation of Aβ1-42.Cell experiments showed that T-D/Que/PEG-PE micelles had low cytotoxicity to PC12 cells.