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Preparation And Characterization Of Camptothecin Supramolecular Micelles With Reduction-triggered Drug Release Profile

Posted on:2014-02-10Degree:MasterType:Thesis
Country:ChinaCandidate:P LuoFull Text:PDF
GTID:2231330398986481Subject:Polymer Chemistry and Physics
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Nanoparticle drug carriers as carriers of conduction or drug delivery are usually made from natural or synthetic polymer materials. It not only can adjust the speed of release, increase the permeability of the biofilm, change the distribution in the body, but also can improve the bioavailability. The drugs were wrapped in nanoparticles or adsorbed on its surface which used as drug carriers. By passive targeting, drug-loaded nanoparticles came into the cell under the cellular uptake to achieve targeted drug or gene delivery. In recent years, polymeric micelles of nano-carriers of a new class are developing. PMs have been proven effective for delivery of anticancer drugs to tumor and reduced delivery to the normal cells. PMs consist of a core and shell structure; the inner core is the hydrophobic part of the block copolymer, which encapsulates the poorly water-soluble drug, whereas the outer shell or corona of the hydrophilic block of the copolymer protects the drug from the aqueous environment and stabilizes the PMs against recognition in vivo by the reticuloendothelial system (RES). Owing to the intermolecular forces such as hydrophobic function, electrostatic force, hydrogen bond and so on, polymeric micelles were formed by amphiphilic polymeric substance in water. PMs possess several strong advantages, such as high loading capacity, structural stability, excellent tissue penetration, long residence time and effectively drugs reaching the target. In this paper, camptothecin incorporated nanoparticles were synthesized and the structure, drug loading, sustained release of the drugs, cytotoxcity in vitro and anti-tumor efficacy in vivo were studied. The details are given as follows.Chapter1:IntroductionIn recent years, owing to effectively providing cancer diagnosis and treatment, nanotechnology has emerged as one of the important drug delivery systems. Small molecule broad-spectrum anti-cancer drugs have been greatly restricted in clinical use because of its poor water solubility, toxic side effects and other shortcomings. By nanotechnology, small molecule drugs were wrapped in polymeric micelles to increase the water solubility and stability of the drugs. These nano-drugs have many advantages including slow release of drugs and targeting the tumor tissue and so on. The view of the chapter will discuss the progress and the mechanism treating diseases of the nanomedicine and nano-carrier, especially the application of polymeric micelles of reduced degradability in the oncotherapy field.Chapter2:Fabrication and characteristic of supramolecular micellesFabrication of supramolecular micelles:Michael addition polymerization occurred between N, N-bis(acryloyl) cystamine (BAC) and mono(6-(2-aminoethyl)amino-6-deoxy)-β-cyclodextrin (CDen) to produce the reduction-degradable polymer of BAC-CDen. And adamantyl-modified polyethylene glycol monomethyl ether (mPEG-Ad) was further encapsulated in it to gain supramolecular micelles of mPEG-Ad@BAC-CDen. The structure of mPEG-Ad@BAC-CDen were characterized by1H NMR and FTIR. The performance of mPEG-Ad@BAC-CDen micelles were confirmed by the methods of fluorescence spectrophotoscopy, UV-vis, DLS and TEM.Chapter3:Fabrication and evaluation of camptothecin incorporated supramolecular micellesmPEG-Ad@BAC-CDen supramolecular micelles had good biocompatibility and water-soluble. In this paper, the drug loading behavior of camptothecin incorporated supramolecular micelles were mainly evaluated. By HPLC measuring mPEG-Ad@BAC-CDen can effectively protect CPT-lactone ring form. CPT loaded mPEG-Ad@BAC-CDen micelles were observed by TEM and DLS. As the results, the micelles of mPEG-Ad@BAC-CDen/CPT were similar with the micelles of mPEG-Ad@BAC-CDen. The micelles of mPEG-Ad@BAC-CDen as a drug carrier can control the drug-release. The toxicity of drug loaded the polymer is lower than the pure CPT. MPEG-Ad@BAC-CDen micelles which have potential applications in the biomedical field are expected to be used as an effective anticancer drug carrier cells.
Keywords/Search Tags:Reduced degradability, Supramolecular micelles, Camptothecin, Cytotoxicity, Stability
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