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Study Based on Disulfide Cross-linked Biomimetic Micelles with Bio-responsiveness

Author: LvLiPing
Tutor: JiJian
School: Zhejiang University
Course: Polymer materials
Keywords: Phosphorylcholine Biological response type Crosslinked micelles Drug carrier Biocompatibility
CLC: R318.08
Type: Master's thesis
Year: 2011
Downloads: 144
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Abstract

Polymeric micelles because of its special core-shell structure is extremely important to a wide range of applications in the biomedical fields such as drug delivery system. Ideal drug carrier in the drug delivery process can be stably exist, and able to achieve rapid and effective release of the drug to reach the targeted position, therefore, for the polymeric micelles anti dilution stability problems when used as a nano microcarrier the release of the drug at the target site, we have adopted the method of crosslinking to enhance the stability of the micelles, and in this procedure simultaneous introduction of biological response of disulfide bridges, constructed based on the biological response of the disulfide crosslinking the type membrane biomimetic micelles and explore its performance. First, glycidyl methacrylate (GMA) as the reactive functional monomer introduced into the the phosphorylcholine groups amphiphilic polymer synthesis, was successfully prepared with 2 - methyl acryloyloxyethyl phosphate bile alkali (MPC) for cell membrane bionic component, methyl acrylate, stearyl acrylate (SMA), GMA is a reactive functional component of the terpolymer is a hydrophobic component. Transmission electron microscopy (TEM), and dynamic light scattering (DLS) test showed that the reactive phosphorylcholine polymer can form a stable polymeric micelles. Cystamine as small molecule crosslinker using bifunctional cross-linked polymeric micelles, dynamic light scattering and determination of the critical micelle concentration (CMC) experimental results show that, the crosslinked micelles anti-dilution stability, The storage stability and solvent resistance are greatly improved. The introduction of a disulfide bond in the cross-linking process gives redox response characteristics of the crosslinked micelles, the exchange process of disulfide bonds with dithiothreitol (DTT), a mercapto group can be crosslinked micelle solution of cross-linking reaction occurs. Simulation results show that intracellular reducing environment, crosslinking of the concentration in the vicinity of CMC in the presence of 10 mM DTT had micelle particle size within 24 h increased from 110.6 nm to 201.2 nm, described the addition of a reducing agent to the cross linked micelle understanding stabilized crosslinked away. Further, the preparation of polymeric micelles as nano-carrier package containing an anticancer drug, and in vitro drug release results showed that the micelles of the disulfide crosslinking can achieve the controlled release of the biological response of the anticancer drug entrapped loaded micelles, i.e., compared with the reducing agent DTT does not exist under the conditions of drug release, the crosslinked DTT reducing environment to more quickly release the drug. Cells Experimental results show that drugs commonly used in the commercial vector ethoxylated castor oil (Cremophor EL) compared to polymer micelles in concentrations up to 250 mg · L-1, can still maintain more than 90% of the cell activity, suggesting that Experiment Preparation of micelles having excellent biocompatibility. The cytotoxicity experiments also show that the drug-loaded micelles crosslinked loaded micelles in a relatively short time (lt; 2 h) endocytosis to inhibit the growth of cancer cells. The prolonged efficacy results showed that the micelles package contained drugs can effectively inhibit the growth of cancer cells. Finally, by fluorescein isothiocyanate-labeled preliminary study endocytic behavior of the cells of the polymer micelles, the micelles in the intracellular distribution provides an effective means for further tracer drug. This can be fluorescently labeled high biocompatibility, stability and biological response type of membrane biomimetic polymer micelles in anticancer drug carriers has potential applications.

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