Synthesis and Characterization of Thermo- and pH-responsive Zwitterionic Copolymers and Their Potential Applications in Controlled Drug Release
碩士 === 國立中正大學 === 化學工程研究所 === 101 === Drug delivery system has led to great improvement in anticancer treatments, including more selective accumulation of drugs at tumor sites and reducing adverse side-effects on healthy normal tissues. The development of a novel drug delivery system is a key factor...
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ndltd-TW-101CCU000630412015-10-13T22:23:53Z http://ndltd.ncl.edu.tw/handle/85343846410112399366 Synthesis and Characterization of Thermo- and pH-responsive Zwitterionic Copolymers and Their Potential Applications in Controlled Drug Release 具溫度與pH敏感性之兩性離子共聚高分子其性質鑑定及藥物釋放潛在應用評估 Hsiang-Ling Wang 王翔玲 碩士 國立中正大學 化學工程研究所 101 Drug delivery system has led to great improvement in anticancer treatments, including more selective accumulation of drugs at tumor sites and reducing adverse side-effects on healthy normal tissues. The development of a novel drug delivery system is a key factor recently. Zwitterionic poly(sulfobetaine methacrylate) (PSBMA) has attracted more attention recently because of its biocompatibility, non-specific protein adsorption and exhibition of an upper critical solution temperature (UCST) in aqueous solution. Herein, we developed a series of dual stimuli-responsive polymer with thermo-responsive poly(sulfobetaine methacrylate) and pH-responsive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) via free radical polymerization. The stimuli-responsive phase transition behaviors of PSBMA-co-PDPA copolymers and PSBMA homopolymer at different pH aqueous solution were measured by UV-visible spectrophotometer. The sulfobetaine based PSBMA-co-PDPA copolymers have showed pH dependent UCST phase transition in aqueous solution. This might be attributed to the significant influence from protonation/deprotonation of DPA segment on the intra- and intermolecular electrostatic interaction and chain conformation between PSBMA and PDPA. Below the UCST, PSBMA-co-PDPA copolymers formed nanoparticles due to electrostatic attraction. Their size and morphology in acidic ( pH< pKa(DPA) = 6.3) and neutral solution were investigated by DLS, SEM and TEM. Through the delicate adjustment of the molar ratios of PSBMA/PDPA, the stimuli-responsive phase transition could be suitable for physiological environment. The curcumin release kinetics in both neutral (pH 7.4) and acidic (pH 2 and pH 5) conditions at 37oC were also monitored. The slower release profile at pH 2 than that at pH 7.4 indicated the nanoparticles is stable in the acidic condition and has the potential for oral drug delivery system. The cytotoxicity of blank PSBMA-co-PDPA in the concentration range of 50 to 500 μg/ml was tested against a cancer cell line, HeLa cells. No significant cytotoxicity was observed at all concentrations. This study indicates that this new series of biocompatible zwitterionic sulfobetaine copolymers have the potential to be applied as drug delivery system. Ching-Yi Chen 陳靜誼 2013 學位論文 ; thesis 109 zh-TW |
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碩士 === 國立中正大學 === 化學工程研究所 === 101 === Drug delivery system has led to great improvement in anticancer treatments, including more selective accumulation of drugs at tumor sites and reducing adverse side-effects on healthy normal tissues. The development of a novel drug delivery system is a key factor recently. Zwitterionic poly(sulfobetaine methacrylate) (PSBMA) has attracted more attention recently because of its biocompatibility, non-specific protein adsorption and exhibition of an upper critical solution temperature (UCST) in aqueous solution. Herein, we developed a series of dual stimuli-responsive polymer with thermo-responsive poly(sulfobetaine methacrylate) and pH-responsive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) via free radical polymerization.
The stimuli-responsive phase transition behaviors of PSBMA-co-PDPA copolymers and PSBMA homopolymer at different pH aqueous solution were measured by UV-visible spectrophotometer. The sulfobetaine based PSBMA-co-PDPA copolymers have showed pH dependent UCST phase transition in aqueous solution. This might be attributed to the significant influence from protonation/deprotonation of DPA segment on the intra- and intermolecular electrostatic interaction and chain conformation between PSBMA and PDPA. Below the UCST, PSBMA-co-PDPA copolymers formed nanoparticles due to electrostatic attraction. Their size and morphology in acidic ( pH< pKa(DPA) = 6.3) and neutral solution were investigated by DLS, SEM and TEM. Through the delicate adjustment of the molar ratios of PSBMA/PDPA, the stimuli-responsive phase transition could be suitable for physiological environment. The curcumin release kinetics in both neutral (pH 7.4) and acidic (pH 2 and pH 5) conditions at 37oC were also monitored. The slower release profile at pH 2 than that at pH 7.4 indicated the nanoparticles is stable in the acidic condition and has the potential for oral drug delivery system. The cytotoxicity of blank PSBMA-co-PDPA in the concentration range of 50 to 500 μg/ml was tested against a cancer cell line, HeLa cells. No significant cytotoxicity was observed at all concentrations. This study indicates that this new series of biocompatible zwitterionic sulfobetaine copolymers have the potential to be applied as drug delivery system.
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author2 |
Ching-Yi Chen |
author_facet |
Ching-Yi Chen Hsiang-Ling Wang 王翔玲 |
author |
Hsiang-Ling Wang 王翔玲 |
spellingShingle |
Hsiang-Ling Wang 王翔玲 Synthesis and Characterization of Thermo- and pH-responsive Zwitterionic Copolymers and Their Potential Applications in Controlled Drug Release |
author_sort |
Hsiang-Ling Wang |
title |
Synthesis and Characterization of Thermo- and pH-responsive Zwitterionic Copolymers and Their Potential Applications in Controlled Drug Release |
title_short |
Synthesis and Characterization of Thermo- and pH-responsive Zwitterionic Copolymers and Their Potential Applications in Controlled Drug Release |
title_full |
Synthesis and Characterization of Thermo- and pH-responsive Zwitterionic Copolymers and Their Potential Applications in Controlled Drug Release |
title_fullStr |
Synthesis and Characterization of Thermo- and pH-responsive Zwitterionic Copolymers and Their Potential Applications in Controlled Drug Release |
title_full_unstemmed |
Synthesis and Characterization of Thermo- and pH-responsive Zwitterionic Copolymers and Their Potential Applications in Controlled Drug Release |
title_sort |
synthesis and characterization of thermo- and ph-responsive zwitterionic copolymers and their potential applications in controlled drug release |
publishDate |
2013 |
url |
http://ndltd.ncl.edu.tw/handle/85343846410112399366 |
work_keys_str_mv |
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