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Synthesis And Properties Of Enzyme Sensitive Amphiphilic Polyphosphazene Drug Carrier

Posted on:2019-01-21Degree:MasterType:Thesis
Country:ChinaCandidate:Z K QuFull Text:PDF
GTID:2381330545961479Subject:Polymer Chemistry and Physics
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The development of drug carriers with good biocompatibility,targeted selectivity and water-soluble increase of hydrophobic insoluble drugs has become a hot topic in recent years.Because of its selective specificity,it can significantly improve the efficacy of anticancer drugs and reduce the toxic and side effects on healthy tissues.Compared with normal tissues,tumor tissue and tumor cells and their microenvironment are significantly different.For example,the integrity of tumor tissue,high expression of cathepsin B and so on.It can be used and the design of drug carrier.Studies have shown that polymer drug carriers,including polymer drug conjugates and polymer micelles,have significant effects on drug delivery and have been applied to clinical trials,which are of great significance in improving the effect of cancer treatment.In this paper,the synthesis and properties of enzyme sensitive two affinity polyphonitrile drug carrier were reviewed.Polyphosphonitrile is designed and prepared,and polyethylene glycol monomethyl ether is a hydrophilic chain segment.Cathepsin B sensitive polypeptide compound is a hydrophobic chain end,and the antitumor drug adriamycin,synthase sensitive two Pro polyphonitrile drug carrier is prepared.The performance of the drug carrier was studied.The contents of this study are as follows:Amino acid as raw material,liquid phase synthetase sensitive peptide.Polyphosphonitrile is prepared by ring opening polymerization of tri-phosphonitrile.The hydrophilic segments of polyethylene glycol monomethyl ether and hydrophobic chain enzyme sensitive peptides are respectively bound onto polyphosphonitrile.And bond with adriamycin,an anticancer drug.Because the drug loaded polymer has a hydrophilic shell and encapsulated hydrophobic drugs,it can self assemble into micelles in aqueous solution.Through passive targeting EPR effect,the tumor site is enriched,and the cathepsin B,which is highly expressed in tumor cells,responds to the broken polypeptide and then releases the drug.It can improve the efficacy and reduce the side effects.NMR(1H-NMR),infrared spectroscopy(FT-IR)and ultraviolet(UV)were used to characterize a series of enzyme sensitive two polyphilic phosphonitrile drug carriers.The minimum critical micelle concentration(CMC)of the drug carrier was obtained by the method of pyrene fluorescence probe,according to the logarithmic plotting curve of the fluorescence intensity and the corresponding copolymer concentration.The drug carrier was analyzed by dynamic light scattering(DLS)and atomic force microscope(AFM),and the size,distribution and existing form of the polymer micelles were obtained.The drug loading was determined by ultraviolet spectroscopy.The hydrodynamic diameters and morphologies of drug loaded micelles were studied by DLS and AFM.In vitro release of drug loaded polymers was studied by simulating human physiological environment and tumor cell microenvironment.The experimental results showed that the cumulative release rate of 72h was 85%in the presence of cathepsin B in the presence of cathepsin B in the presence of cathepsin in the case of pH=5,which was 3 times that of the enzyme without the enzyme and in the case of physiological pH.It was proved that the drug loaded polymer was sensitive to cathepsin B.It can achieve specific release and reduce toxic and side effects.
Keywords/Search Tags:cathepsin B, polyphonitrile, two affinity drug carrier, enzyme sensitive peptide
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