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Study On The Usage Of Polyelectrolyte Modified Graphite For Transport Of Anti-cancer Oral Drugs

Posted on:2018-03-28Degree:MasterType:Thesis
Country:ChinaCandidate:D C JiaFull Text:PDF
GTID:2334330512990435Subject:Medicinal chemistry
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Grapheme Oxide(GO)is a new type of drug carrier.GO has been widely used in oral absorption of intravenous drugs in recent years,so as to improve the bioavailabil-ity of insoluble drugs.In this paper,GO is prepared by using modified new method,and its surface was wrapped modified by polyelectrolyte by the principle of charge attraction.To study the effect of polyelectrolyte modified GO on the oral transport of anticancer drugs and its mechanism were studied,and to investigate the effects of polyelectrolyte modified GO on the oral transport of anticancer drugs was investigate and to study the effects of polyelectrolyte modified GO on the oral transport of anticancer drugs and other studies by electron microscopy,particle size analysis,in vitro release,pharmacokinetic st-udy and MTT.Firstly,the modified Hummers method was used to obtain oxidized graphite,and the GO was prepared by ultrasonic stripping.The morphology and chemical structure of the GO were characterized by scanning electron microscopy(SEM)and transmission electron microscopy(TEM),fourier transform infrared spectroscopy(FTIR)and ultraviolet spectroscopy(UV).The results showed that the prepared GO was a nanoscale carrier with a lamellar structure.The experimental procedure for preparing GO is simple,and the safety is improved compared to the previous method of preparing GO.The entrapment efficiency of GO to DOX was 87.58%,and the encapsulation efficiency of PYM was 82.05%.This is due to the GO structure containing more oxygencontaining functional groups,so to a large extent increasing the ability of GO drug delivery;GO-DOX and GO-PYM preparation group in vitro release analysis results,the preparation group at different p H The results showed that the two groups showed the same release trend,and the two groups reached the highest cumulative release at 60 hours at p H2.3,indicating that the release behavior showed a certain p H dependence PAA-CYs was studied by single factor method.The optimal method of PAA binding to CYs was studied.The results showed that the addition of EDC content,p H and temperature could affect the binding of PAA and CYs and affect the content of disulfide bonds in PAA-CYs.The Appropriate method was screened out by the method of Ellman method.Making PAA-CYs the highest yield.PAA-CYs/PAH-GO-DOX and PAA-CYs/PAH-GO-PYM were produced with GO-DOX and GO-PYM combined with mercapto polyelectrolyte by charge-attraction.The results of the Electron micros-copy show a relatively stable structure.The particle size of the two groups was about 700 nm and 750 nm,respectively.Zeta potential can be seen from the Zeta potential of-39.8m V and-34.1m V,on the one hand shows the stability of the preparation is good,on the other hand also proved that the preparation group with a negative charge,consistent with the previous theoretical analysis;By detecting the free thiol group can be divided into two groups of formulations are not containing free sulfhydry,can be confirmed side of the PAA and CYs binding completely.Finally,DOX group was treated with GO-DOX group and PAA-CYs/PAH-GO-DOX group in PYM group,GO-PYM group and PAA-CYs/PAH-GO-PYM group respectively.By data analysis,it was found that all the preparation groups showed high resistance to strong acid,and proved that the encapsulation of the two layers of polyelectrolytes could be used to protect the drug in the strong acidic environment.Finally,the rats were treated with intestinal absorption test and MTT assay.In the pharmacokinetic study,the AUC value of the preparation group was more than that of the raw drug by65.57mg/L·h,and T1/2 also extended by 0.519 h,better than the raw drug.It showed a sustained release effect.The results of MTT assay showed that the PCPGP preparation group for cancer cell A549 mortality compared to PYM group decreased by 2.40%.The IC50 dose of PCPGP preparation group was 24.28?M higher than that of PYM group,which was 29.42?M and also higher than that of GO-PYM group,indicating that PCPGP preparation group in the same concentration of 24 h time shows a certain sustained release effect.Finally,the PCPGP preparation group effectively improved the oral bioavailability of anticancer drugs.
Keywords/Search Tags:Grapheme Oxide, doxorubicin, polyelectrolyte, PYM, new dosage form
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