Preparation And Characterization Of PH-responsive Dextran Nanomicelles

With the change of the surrounding environment,environment-sensitive polymer micelle structure can produce accurate response.As a drug carrier,it can carry out the payload on hydrophobic drugs and realize the release of drugs in response to the environment,which is valuable in the application of biomedical field.Dextran,which is an electrically neutral natural polysaccharide with excellent biological safety,has been widely used in clinical practice as a substitute for plasma.In addition,its molecular structure contains a large number of free hydroxyl groups,which is easy to be chemically modified.Therefore,dextran is a natural polymer commonly used in the preparation of micellar drug carriers.The preparation of dextran nanomicelles is usually obtained by self-assembly of amphiphilic dextran derivatives in selective solvents to form a core/shell nanostructure with a hydrophobic core and a hydrophilic shell.The solubility and stability of fat-soluble drugs can be increased by encapsulating the hydrophobic core.However,the current preparation methods of amphiphilic dextrans and their micelles usually involve the use of a large number of organic solvents,complex chemical modifications and multi-step reaction processes.Therefore,this thesis chooses the glucan as hydrophilic chain segments,oil amine as the hydrophobic chain,therefore build a kind of glucan nano micelle preparation method based on the aldehyde amine Schiff-base reaction.Furthermore,as a drug carrier loading oil soluble drug doxorubicin(DOX),we studied its performance and pHresponsive drug release behavior,the main research content is as follows:1.The aldehyde dextran was modified by sodium periodate;the aldehyde dextran was used as hydrophilic chain segment and the oleamine as hydrophobic chain.The aldehyde dextran derivatives with amphiphilic properties were prepared by the aldehyde-amine Schiff-base reaction,and the micelle structure was formed by selfassembling in the reaction system.The preparation conditions(ultrasonic time,grafting rate,organic phase,emulsification method,aldehyde dextran concentration,etc.)of the dextran micelles were explored,and the best preparation conditions were determined.The micelle structure has the characteristics of small particle size,good dispersion and good spherical morphology.2.The critical concentration(CMC)of the dextran micelle was determined by pyrene fluorescence probe method.The CMC of the dextran micelle was 0.00139 mg/ml.We further used fluorescence resonance energy transfer(FRET)to establish a kind of method which is able to monitor the behavior of micelle reunion the article introduces the fluorescent dyes in the aldehyde glucan Cy5.0 and Cy5.5 to prepare glucan which containing FRET fluorescence probe for nano micelle,Through the fluorescence spectra of glucan nano micelle monitoring,the micelle formation process with the change of time is studied.The results show that reaction system is able to form the micelle structure at about 12 h The microspheres containing FRET dextran were characterized by scanning electron microscopy(SEM)and showed good spherical morphology.3.The Schiff base bond in the structure of the dextran nanomicelles makes it express a certain pH-environmentally response.In this paper,through the desalination and acidification of the anticancer drug DOX-HCl,we choose DOX-HCl as the drug model to obtain the hydrophobic drug DOX.DOX was encapsulated in the hydrophobic core of the micelle with the dextran nanoparticles as drug carrier,and a drug-carrying dextran nanomicelle containing hydrophobic DOX was prepared(DOX@Dex).The drug loading of micelles was measured and calculated by ultraviolet spectrophotometer,and the drug loading rate was 25.2% and 0.5%.DLS and SEM images showed that the drug-loaded dextran nanoscale micelles displayed similar morphology and structure compared with pure dextran nanoscale micelles.In-vitro drug release experiments showed that the drug release behavior of drug-loaded dextran nanomicromicelles performed a certain response to pH environment.With the increase of pH value in the buffer,the drug release rate decreased,and the cumulative drug release amount also decreased.In pH5.0 buffer,the amount of cumulative drug release was up to 49.48%in 90 h.The drug release process of drug-loaded nano-micelles is characterized by "sudden release" phenomenon,and the drug release rate will gradually flatten as time goes by.4.The hydrophobic superparamagnetic iron oxide(SPIO)was supported by the obtained dextran nanoscale micelles.The SPIO particles were dissolved by n-hexane,and then the SPIO was mixed with oleoamine solution and dropped into the aqueous solution of aldehydes dextran under the condition of ultrasound to obtain the nanomicelles in the reaction system.The SPIO-supported micelles express similar morphology and structure compared to those pure dextran nanoscale micelles and perform a good dispersion.