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Preparation Of Intelligent Nanocarriers Based On Cyclodextrin Polymer For Controlled Drug Release

Posted on:2019-06-12Degree:MasterType:Thesis
Country:ChinaCandidate:Y R GaoFull Text:PDF
GTID:2321330542981927Subject:Chemistry
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In recent years,cancer has become a major disease that endangers human health and can seriously damage normal cells when using traditional treatment methods.However,the intelligent nano drug delivery system can achieve high drug loading and controlled drug release,greatly reducing toxic side effects on the human body.Currently,environmental-responsive nanocarriers are widely used for the delivery of anticancer drugs because of their good biocompatibility,biodegradability,targeting and stimuli-responsivity.In this paper,environment-responsive nanocarriers were prepared by electrostatic interaction and host-guest recognition of natural polysaccharide chitosan,sodium alginate,?-CD,NIPAM,BM,?-CL and so on.And the in vitro release studies were researched with model anticancer drugs,such as 5-Fu,DOX,IND,and DS.Sodiumalginate-graft-poly?N-isopropylacrylamide??SA-g-PNIPAM?and chitosan-graft-?-cyclodextrin?CS-g-CD?were prepared by graft modification of natural polysaccharide chitosan and sodium alginate.Thermo-and pH-sensitive polyelectrolyte complex?PEC?nanoparticles with CS/SA as the core,thermo-sensitive PNIPAM and?-cyclodextrin as the mixed shell were prepared by electrostatic interaction between-NH3+of chitosan and-COO-of sodium alginate.The structure,morphology and particle size of nanoparticles were characterized by fourier transform infrared spectroscopy?FTIR?,X-ray diffraction?XRD?,transmission electron microscopy?TEM?and laser particle analyzer.The results show that the PEC nanoparticles exhibit regular spherical with the diameter of 50 nm and high drug loading and entrapment efficiency for both DOX and 5-FU.The in vitro release demonstrated that the DOX-loaded PEC nanoparticles exhibited an enhanced sustained manner within 72h.The release of DOX from nanoparticles increased with the increase of temperature and ion strength or the decrease of pH.The maximum drug release was80.17%at the temperature of 40°C,ion strength of 0.3 M and pH of 2.0.pH-Sensitive complex micelles were developed based on the host-guest recognition from chitosan-graft-?-cyclodextrin?CS-g-CD?and benzimidazole modified poly??-caprolactone??BM-PCL?for controlled drug release.The structure,morphology and particle size of complex micelles were confirmed by fourier-transform infrared spectroscopy?FTIR?,X-ray diffraction?XRD?,transmission electron microscopy?TEM?and laser particle analyzer.The size of micelles was about 200 nm with the core formed by BM-PCL/?-CD and the shell composed of chitosan.Doxorubicin?DOX?,a model anticancer drug,was effectively loaded into the complex micelles via hydrophobic interactions.The encapsulation efficiency of DOX in complex micelles was up to 75%.The release of DOX from complex micelles was suppressed at neutral pH solutions due to the stability of micelles but accelerated at acidic solutions and high temperatures.These sensitive complex micelles might possess potential applications as intelligent nanocarriers for anticancer drug delivery.A well-defined double hydrophilic poly??-cyclodextrin?-containing diblock copolymer PEG-b-PCD was synthesized by atom transfer radical polymerization?ATRP?.Complex polymeric micelles with defined core-shell structure were formed based on the host-guest interactions between?-CD and hydrophobic benzimidazole modified poly??-caprolactone??BM-PCL?.The hydrophobic PCD/BM-PCL resided in the core of micelles,while the hydrophilic poly?ethylene glycol??PEG?chains acted as the micelles shell.The micelles exhibited regular spherical with the diameter of 255nm.The drug loading efficiency of micelles for doxorubicin?DOX?was high due to the hydrophobic core containing poly??-CD?.The in vitro release demonstrated that DOX-loaded polymer micelles exhibited an enhanced sustained manner after an initial burst release.The release of DOX from complex micelles was accelerated as the pH reduced from 7.0 to 2.0 and the temperature increased from 25 to 37°C.These results indicate that the complex micelles have potential applications in controlled drug delivery.
Keywords/Search Tags:nanocarriers, cyclodextrin polymer, host-guest recognition, sensitive polymer micelles, drug release
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