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Synthesis Of Polyaspartamide/Poly(Glycerol Methacrylate)s Derivatives For Construction Of Reverse Micelles And Target Drug Delivery System

Posted on:2016-06-27Degree:MasterType:Thesis
Country:ChinaCandidate:D E LiuFull Text:PDF
GTID:2191330461989645Subject:Applied Chemistry
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AbstractPoly(amino acid)s and their derivatives have been known to exhibit interesting biochemical properties on account of their superior biocompatible, biodegradability and non-toxicity. They are used in various fields including biomedicine, pharmaceuticals, cosmetics and agrochemicals. In this study, a series of amphiphilic graft copolymers based on biodegradable and biocompatible poly(aspartic acid)s(PASP) were synthesized by a successive aminolysis reaction of polysuccinimide using octadecylamine/dodecylamine, and ethylenediamine-β-cyclodextrin /ethanediamine. The chemical structures of copolymers were confirmed by FT-IR and 1H NMR spectroscopy.Reverse micelles(RMs) has been widely used as nanospacemicroreactors and soft template for preparing inorganic nanoparticles, carriers for drugs, and they can be used to selectively enrich biomarker peptides and protein fragments from human serum and selectively extract/fractionate peptides based on their isoelectric points. The self-assembly behaviour of the amphiphilic graft poly(amino acid) derivatives have been investigated to form regular micelles in water. However, to the best of our knowledge, investigations about reverse micellization of them have not been reported. Large compound reverse micelles consisting of numerous small reverse micelles based on PASP derivatives with polar cores and hydrophobic shells were formed in octanol solution. The RMs showed various particle sizes based on the different length of hydrophobic alkyl chains and molecular weight of polysuccinimide, as determined by dynamic light scattering. Interestingly, the particle size of micelles showed temperature dependence, the diameter decreased continuously with rising temperature. Their morphology and assembly property were characterized using scanning electron microscope, transmission electron microscopy and fluorescence spectroscopy. The reverse micelles were extremely efficient in extracting Congo red from water into octanol, exhibiting a potential application as delivery vehicles in the pharmaceutical and cosmetic fields, and as nanocontainers for separation of inorganic molecules as well.Nano vehicles such as dendrimers, vesicles, liposomes, micelles and inorganicmaterials have been widely employed as drug delivery systems(DDS) in cancer therapy. Nevertheless, these traditional DDS are typically “one trick ponies” and their sole role is to deliver drugs into cancer cells. Additionally, these DDSs are invisible and difficult to trace after they enter the cells and release the drugs. We seek to develop traceable nano formulations in order to closely monitordelivery.Herein, we developed a new DDS using folic acid grafted amino poly(glycerol methacrylate) derivatives(PGMA-FA) and typical AIE-active molecules, tetrakis(4-carboxyphenyl)ethylene(TPE-COOH4) to fabricate a self-assembly micelle with aggregation-induced emission(AIE).Amino cationic polymerselectrostatically interact with negatively charged TPE-COOH4 molecules to form aggregations, leading tofluorescence enhancement, to make the nanocarrier visible. The positively charged amino polymer can take the loaded drug into the cell, and folic acidas a targeting moiety of tumor cells can help drugs into tumor cells more effectively, improve the therapeutic effect. Carboxylated negative charged TPE can interact with positive charged amino moiety of PGMA and DOX to form nanoparticles with diameters in the range 30-40 nm. The DDS maintain the integrity of the AIE properties possessed by TPE, and generate FRET effect with DOX. On the other hand, the introduction of folic acid improved the drug targeting function. The vitro release studies showed that the DDS at lower p H(p H = 5.0) release more DOX than at higher p H(p H = 7.4), exhibiting that the complex was capable of release the cargo at lower p H tumor site.
Keywords/Search Tags:Poly(aspartic acid)s, Reverse micelle, Tetraphenylethylene, Poly(glycerol methacrylate), Doxorubicin, Drug delivery system
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