合成一pH應答型磁性微胞藥物載體應用於抗發炎之研究

黃尹佐

doi:10.6840/cycu201700916

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合成一pH应答型磁性微胞药物载体应用於抗发炎之研究

Synthesis of pH response magnetic micelles drug carrier for anti-inflammation study

黄尹佐 , 硕士　　导师：葛宗融　　

繁体中文 DOI： 10.6840/cycu201700916

药物载体；温度应答微胞； pH应答微胞；磁标的微胞；双重标的；抗发炎反应； Drug carrier ； Thermo response micelles ； pH response micelles ； Magnetic micelles ； Dual-targeting ； Anti-inflammatory response

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摘要 │ 参考文献 (54) │ 国际计量

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Atherosclerosis symptoms are repetitive local inflammation and relative lowering of pH value in the focal area. Recent studies have developed anti-inflammatory drugs for atherosclerosis, however there has never been a breakthrough on the treatment efficacy of these drugs. One of the drug, hesperetin has been demonstrated as an inflammation response suppressor and could be used for atherosclerosis treatment. The drug carrier micelles, not only can be used to control drug delivery, but also to prolong the circulating time of the drug and reduce its side effect. The aim of this study was to investigate the chemical synthesis, biocompatibility and in vitro drug delivery response of pH and temperature responsive magnetic micelles. The pH and temperature magnetic responsive micelles, poly( N-isopropylacryamide- co- N,N-dimethylacrylamide -co- 10 undecanoic acid ) / CM-Dextran Fe3O4, were synthesized to be a dual-targeting of the drug carrier by grafting hydrophilic CM-Dextran Fe3O4 onto poly(NIPAAm-co-DMAAm-co-UA). Then, the anti-inflammation responsive drug, hesperetin, was encapsulated by micelles using membrane dialysis method to obtain Hesperetin-loaded P10DF10. The micelles were characterized by Fourier transform infrared spectroscopy, 1H-NMR, Thermo gravimetric analyzer and Superconducting Quantum Interference Device Magnetometer. The morphology and particle size of micelles was observed by Transmission electron microscopy and Dynamic light scattering. Fluorescence analysis indicated that the micelles had a low critical micelle concentration of 0.0315 wt% in aqueous media. The low critical solution temperature of the micelles is in pH 6.6 at about 37.76 °C and in pH 7.4 at about 41.70 °C. The biocompatibility of micelles in different concentration of 500, 1000 and 2000 g/ml were confirmed by cytotoxicity study. Results showed that there were no significant cell cytotoxicity in setting concentration of micelles. Hesperetin-loaded micelles were stable in normal body pH value and temperature, but could be deformed at below normal body pH value to trigger the release of Hesperetin. Based on these results, the present study has successfully polymerized the P10DF10 micelles that have the ability to carry and release drugs. Dual-targeting anti-inflammatory characteristic of micelles confirmed the magnetic targeting and pH responsivity of hesperitin-loaded micelles. It is believed that the P10DF10 micelles have the feasibility for biomedical applications.

参考文献 ( 54 ) 〈TOP〉

[1] 行政院卫生署. 民国105死因统计结果分析. 2017.
连结：
[3] L. Zhang, R. Guo, M. Yang, X. Jiang, B. Liu, “Thermo and pH dual‐responsive nanoparticles for anti‐cancer drug delivery. ” Advanced Materials, vol. 19, pp. 2988-2992, 2007.
连结：
[4] G. H. Gao, J. W. Lee, M. K. Nguyen, G. H. Im, J. Yang, H. Heo, P. Jeon, T. G. Park, J. H. Lee, D. S. Lee, “pH-responsive polymeric micelle based on PEG-poly (β-amino ester)/(amido amine) as intelligent vehicle for magnetic resonance imaging in detection of cerebral ischemic area.” Journal of controlled release, vol. 155, pp. 11-17, 2011.
连结：
[5] M. Das, C. Wang, R. Bedi, S. S. Mohapatra, S. Mohapatra, “Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.” Nanomedicine: Nanotechnology, Biology and Medicine, vol. 10, pp. 1539-1548, 2014.
连结：
[6] N. Schleich, C. Po, D. Jacobs, B. Ucakar, B. Gallez, F. Danhier, V. Préat, “Comparison of active, passive and magnetic targeting to tumors of multifunctional paclitaxel/SPIO-loaded nanoparticles for tumor imaging and therapy.” Journal of Controlled Release, vol. 194, pp. 82-91, 2014.
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DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。