| Xylan is the second most abundant biopolymer cellulose in the world.Recently,it has been used due to its good biocompatibility,degradability and non-toxic properties.Polysaccharides contain a variety of functional groups that are better than synthetic polymers for drug coupling.With the continuous development of drug delivery system,solid dispersion,liposome entrapped cyclodextrin complex,the micro capsule,nanoparticles,nano suspension agent and polymer micelle drug delivery system such as common all can significantly enhance the treatment effect of drugs,and reduce the side effects,more than a carrier of drug delivery system of raw material,such as quercetin(QT)flavonoids,itself has been demonstrated to inhibit the action of the drug pump,can very good inhibition of P-gp glycoprotein,to improve the solubility of difficult soluble drugs,improve its oral bioavailability drugs provides a good application prospect.This paper synthesized the quercetin(QT)-single succinate introduction of carboxylic acid(-COOH)group-function,then through carbon two imine reaction(EDC/NHS)makes the carboxyl after activation of quercetin endpoint and hydroxy activation occurs after esterification reaction of water soluble Xylan,quercetin is obtained by desolvation method-Xylan polymer carrier(QT-Xylan),and through infrared spectrum(FT-IR)and nuclear magnetic resonance hydrogen spectrum(1H-NMR)on the synthesis of the final product QT-Xylan carrier were characterized.Carrier have been detected in the infrared spectrum,compared with the Xylan in 1735 cm-1 ester key characteristics of a significant peak,in the nuclear magnetic resonance,compared with the Xylan carrier in 6.5-8.0 ppm QT characteristic peak of benzene ring,due to the characteristic peaks were detected corresponding,thus prove that the esterification reaction,synthesis of a new type of polymer carrier QT-Xylan.Through the use of fluorescence spectrophotometer,the fluorescence values of QT-Xylan carriers with different concentrations were measured respectively,and the critical micelle concentration(CMC)value of the micelles formed by the polymer carrier QT-Xylan was about 0.87 mg/mL.QT-Xylan was used to evaluate the safety of zebrafish.The results showed that the carrier concentration at 0.01-1.5 mg/mL had no obvious toxic effect on the organism.In this paper,the synthesized QT-Xylan carrier has good surfactant properties and is applied to the preparation of nano suspension.Firstly,the carrier was loaded with CoQ10 by shear high pressure homogenization method,and the preparation process was optimized by single factor experiment.By studying the homogeneous cycles,homogeneous circular pressure,copolymer concentration,the quality of the copolymer and the CoQ10 than four factors that affect the particle size,so as to get the best optimization process:when the homogeneous cycles for 7 times,homogeneous circular pressure of 600 bar,copolymer concentration of 1 mg/mL,copolymer with CoQ10 when the mass ratio of 1:1,get the minimum size of the nanometer suspending agent,to ensure its accuracy,so the five parallel experiments under the optimum conditions,the measured average particle size of(166.7±18.6)nm,potential for(-14.54±1.5)mv.It was characterized by FT-IR,SEM,XRD,TG and DSC,and the results showed that the drug-carrying nanometer suspension agent had structural characteristics different from that of Co Q10.In addition,in vitro dissolution and bioavailability experiments were carried out,and the experimental results showed that the release effect of drug-loaded nanometer suspension agent in gastric and intestinal fluid was significantly improved compared with that of CoQ10 powder and physical mixture.In the rat experiment,the oral bioavailability of the drug-loaded nano-suspension agent was 2.64 times higher than that of the original drug CoQ10.Results show that through the preparation and four factors of affecting the particle size is optimized,can get the optimal conditions of new nano suspending agent,increase its smaller particle size,surface area.And through the cells absorb experiment,make the QT-Xylan carrier and drug-loading nanoparticle suspension formulation and P-gp glycoprotein inhibitor Verapamil and quercetin respectively comparing experiment,result shows that the synthesis of QT-Xylan and nanometer suspending agent has obvious inhibition to the P-gp glycoprotein,and inhibition is better than Verapamil(Verapamil)and quercetin(QT).In addition,the zebrafish experiment showed that there was no obvious toxic effect when the carrier concentration was 1mg/mL,so the water solubility of CoQ10 could be effectively increased and its oral bioavailability could be effectively improved.In this paper,the synthesized QT-Xylan carrier has good amphiphilic block copolymer properties and can self-as SEM able to form polymer micelles in water.The drug-carrying polymer micelles(QT-Xylan-CoQ10)were prepared by solvent volatilization method,.and their physical and chemical characterization,such as FT-IR,SEM,XRD,DSC,TG,etc.,were tested,and their in vitro release and oral bioavailability were analyzed.The experimental results are as follows:firstly,polymer micelles are self-as SEM bled in aqueous solution when the concentration of the synthesized carrier reaches above the critical micelle concentration.Second,QT-Xylan-CoQ10 prepared by solvent evaporation method,CoQ10 soluble in ethanol,by dropping into the polymer micelle in aqueous solution,the concentration of copolymer,the amount of CoQ10,and the proportion of water and ethanol three factors on the micellar delivery of CoQ10 drug-polymer interactions and the influence of coating rate,can get the optimal condition:copolymer concentration of 1 mg/mL,for 20%of the total amount of CoQ10,water:ratio of 9:1,ethanol and validation experiments under the optimum conditions,the experimental results are as follows:drug loadings of 11%plus or minus 0.5%,the coating at a rate of 36%plus or minus 0.3%.FTIR,SEM,XRD,DSC and TG were used to characterize the drug-loading micelles in the experiment.The results showed that the drug-loading polymer micelles had structural characteristics different from those of coenzyme Q10,which proved the synthesis of QT-Xylan-CoQ10.And through the cell uptake experiment,QT-Xylan carrier and drug loading micelles were compared with P-gp glycoprotein inhibitors Verapamil and quercetin respectively.The results showed that the synthesized QT-Xylan and drug loading polymer micelles had significant inhibitory effect on p-gp glycoproteins,and the inhibitory effect was significantly better than Verapamil and quercetin(QT).The zebrafish experiment showed that the optimal concentration of 1 mg/mL in the vector had no obvious toxicity.In addition,dissolution and bioavailability were tested in vitro.The results showed that the dissolution rate of QT-Xylan-CoQ10 in vitro was significantly higher than that of coenzyme Q10,and the bioavailability of QT-Xylan-coq10 orally was about 3.07 times that of the original drug. |
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