| Micelles can be synthesized from amphipathic polymer through certain method under specific preparation process. This kind of micelles have a lot of advantages in pharmaceutical field, like low toxicity, small size, high drug loading amount, long blood circulation time and the property of both active and passive targeting and so on. This paper mainly focused on the design and synthesis of encapsuled doxorubicin (Dox) micelles drug delivery systems. This disassemblable micelles for intracellular delivery of doxorubicin were developed based on a reduction-degradable amphiphilic polysuccinimide-g-polyethylene glycol graft copolymer containing disulfide linkages throughout the main chain. In-depth research on the structure of the micelles, drug loading amount, drug release behavior, toxicity on extracorporal cells and phagocytosis of cells, image formation effect of magnetic resonance imaging (MRI) was carried on.The specific content is as following:Chapter1:IntroductionAs an integrated technology system, nano-technology has received enormous attractions of all fields for its unique properties. In traditional pharmaceutical field, the isolation of diagnosis and treatment would not only increase the expense of patients, but also increased physical and psychological burden to them. The traditional micromolecular broad-spectrum anti-cancer drugs have limited extent in clinical application for their poor water-solubility and toxic and side effect despite of their high anti-cancer effect. The micelles which were synthesized by combining and functionalizing micromolecular drugs and high polymer carrier can enhance the solubility in water. Moreover, they have advantages, such as slow drug-release rate, tumor targeting etc. In recent years, nanotechnology has been providing more and more optional effective methods for the diagnosis and treatment of cancer, especially since development of the multi-functional polymer micelle system. This chapter summarizes the mechanism, properties and the latest development of nanodrugs, especially the properties and anti-cancer treatment applications of multi-functional polymer micelle nanodrugs. Chapter2:The preparation and characterization of MRI visible superstable doxorubicin incorporated.Fe3O4was prepared through classic route in the existence of dibenzyl ether, iron (III) acetylacetonate (Fe(acac)3),1,2-hexadecanediol, oleic acid and oleylamine. The amino-acid derivatives of poly (ethylene glycol)(mPEG-ss-NH2) and dopamine (DA) were successively grafted to the main chain of poly (L-succinimide)(PSI) to obtain the product mPEG-ss-NH-g-PAsp-DA. The doxorubicin micelle drugs (mPEG-ss-NH-g-PAsp-DA-Fe3O4-Dox) were got from self-assembly reaction of mPEG-ss-NH-g-PAsp-DA, Fe3O>4and doxorubicin (Dox). The mPEG-NH-g-PAsp-DA-Fe3O4-Dox were synthesized through the same method. The structures of the products were characterized by1H NMR, and the nature of the polymeric nanomicelle was determined by MMVFTB, fluorescence spectra, ICP-AES, UV-vis, fourier transform infrared (FT-IR), DLS and TEM method.Chapter3:The test on MRI visible superstable doxorubicin incorporated.The vitro release experiments showed that core-shell micellar Dox drugs prepared by using mPEG-ss-NH-g-PAsp-DA, Fe3O4particles and Dox had good effect to release doxorubicin slowly. The toxicity-testing and phagocytic experiments of doxorubicin, micellar Dox and its carrier showed that mPEG-ss-NH-g-PAsp-DA-Fe3O4-Dox micellar drug with doxorubicin had strong antitumor activity in tumor tissue and good slow-release effect. In addition, by evaluating the result of MRI experiments of micellar Dox drugs in nude mice, we could conclude that this doxorubicin nano micelle drug had better targeting and obvious MRI imaging effect in nude mice and had the function to diagnose and treat vivo tumor synchronous MRI angiography and monitor the delivery of micelle medicine carrying system and its distribution in vivo. |
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