pH/Thermo-Responsive Cross-Linked Copolymer/Drug Complex Micelles for Intracellular Drug Delivery

碩士 === 國立清華大學 === 生醫工程與環境科學系 === 100 === In this study, the complex micelles were formed by electrostatic interaction between hydrophilic anticancer drug doxorubicin (DOX) and graft copolymers. The graft copolymers comprising acrylic acid and 2-methacryloylethyl acrylate (MEA) units as backbone and...

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Bibliographic Details
Main Authors: Chang, Yu-Jen, 張佑仁
Other Authors: Chiu, Hsin-Cheng
Format: Others
Language:zh-TW
Published: 2012
Online Access:http://ndltd.ncl.edu.tw/handle/09089266846034161376
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Summary:碩士 === 國立清華大學 === 生醫工程與環境科學系 === 100 === In this study, the complex micelles were formed by electrostatic interaction between hydrophilic anticancer drug doxorubicin (DOX) and graft copolymers. The graft copolymers comprising acrylic acid and 2-methacryloylethyl acrylate (MEA) units as backbone and both poly(N-isopropylacrylamide) (PNIPAAm) and poly(ethylene glycol) (mPEG) as the grafts were synthesized. These micelles contain high stability by interchains cross-linking. After cross-linking, the particle size of polymeric complex micelles were ca. 53 nm and could be achieved high drug encapsulation efficiency (ca. 80 wt%) and loading content (ca. 40 wt%). In pH-triggered release, DOX were obviously released at pH 4.7 via the protonation of AAc residues on the copolymers, however, DOX would be contained in the micelles at pH 7.4. Besides, the released profile of these micelles was also thermal response. Because of the PNIPAAm on the copolymers, the released profile of micelles would be enhanced when the surrounding temperature was raised. In vitro cytotoxicity tests demonstrated the copolymers used in polymeric complex micelles were nontoxic while DOX-loaded polymeric complex micelles had well toxicity against Hela cells. Moreover, flow cytometry and confocal microscopy also showed the cellular uptake of polymeric complex micelles by Hela cells. These results indicate that these polymeric complex micelles could be provided with pH/thermo-triggered release profile and have highly potential in drug delivery system.