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    韩克, 张国颖. 双重响应两亲性聚前药的合成及其在药物控释方面的应用[J]. 功能高分子学报, 2018, 31(2): 98-107, 127. doi: 10.14133/j.cnki.1008-9357.20180101001
    引用本文: 韩克, 张国颖. 双重响应两亲性聚前药的合成及其在药物控释方面的应用[J]. 功能高分子学报, 2018, 31(2): 98-107, 127. doi: 10.14133/j.cnki.1008-9357.20180101001
    HAN Ke, ZHANG Guo-ying. Synthesis of Dual Responsive Amphiphilic Polyprodrug and Its Application in Controlled Drug Release[J]. Journal of Functional Polymers, 2018, 31(2): 98-107, 127. doi: 10.14133/j.cnki.1008-9357.20180101001
    Citation: HAN Ke, ZHANG Guo-ying. Synthesis of Dual Responsive Amphiphilic Polyprodrug and Its Application in Controlled Drug Release[J]. Journal of Functional Polymers, 2018, 31(2): 98-107, 127. doi: 10.14133/j.cnki.1008-9357.20180101001

    双重响应两亲性聚前药的合成及其在药物控释方面的应用

    Synthesis of Dual Responsive Amphiphilic Polyprodrug and Its Application in Controlled Drug Release

    • 摘要: 通过可逆加成-断裂链转移(RAFT)聚合制备了能够对紫外光和还原环境进行双重响应,以聚乙二醇为亲水嵌段、以侧基中分别含有邻硝基苄硫醚结构的甲基丙烯酸酯衍生物单体及含二硫键结构的喜树碱(CPT)前药单体的共聚嵌段为疏水嵌段的两亲性聚前药。采用紫外-可见吸收光谱和动态光散射跟踪研究了由该聚前药自组装得到的复合囊泡组装体的光响应特性及喜树碱原药分子的释放过程。结果表明,紫外光照可以有效促进CPT的释放,经紫外光照20 min后,CPT在96 h内的累积释放量可达近60%。

       

      Abstract: Polymeric assemblies capable of in-situ constructing redox microenvironments in the hydrophobic domains were designed and fabricated to promote the release of covalently conjugated camptothecin (CPT) drug molecules. The ultraviolet (UV) and redox responsive amphiphilic polyprodrug diblock copolymer, PEG-b-P(NTMA-co-CPTM), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, in which the hydrophilic block was polyethylene glycol (PEG) and the hydrophobic block was copolymerized from two kinds of stimuli-responsive methacrylate derivative monomers, UV-responsive NTMA monomer and redox-sensitive CPTM monomer. In the side group of (2-(3-(4, 5-dimethoxy-2-nitrobenzyl)mercapto-propanamido)ethoxycarbonylamino)ethyl methacrylate (NTMA) monomer, o-nitrobenzyl thioether moiety was introduced to protect the mercapto group; while in the side group of CPTM prodrug monomer, CPT drug moiety was linked to the ethyl group of ethyl methacrylate via disulfide linkage. The chemical and chain structure of the corresponding monomers and diblock polymers were characterized by Nuclear Magnetic Resonance (NMR), High Performance Liquid Chromatography (HPLC), Electron Spray Ionization Mass Spectrometry (ESI-MS) and Gel Permeation Chromatography (GPC). The prepared amphiphilic PEG-b-P(NTMA-co-CPTM) diblock polyprodrug copolymer could self-assemble into compound vesicles in aqueous solution, as confirmed by Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS) measurements. The dual responsiveness of the P(NTMA-co-CPTM) compound vesicles and the release of CPT were monitored via Ultraviolet-Visible (UV-Vis) spectroscopy and DLS. It was found that under UV irradiation, in the side chains of P(NTMA-co-CPTM) blocks, mercapto groups could be decaged due to the photo-cleavage of the o-nitrobenzyl thioether moieties, thus in-situ constructing reductive microenvironments in the hydrophobic domains of the compound vesicles. Then, CPT drug molecules were released via the exchange reaction between the decaged mercapto groups and the adjacent disulfide linkages. After being subjected to UV irradiation for 20 min, the cumulative release of CPT drug molecules within 96 h from PEG-b-P(NTMA-co-CPTM) compound vesicles was as high as 60%, comparable to the result obtained within the same duration time after addition of 5 mmol/L glutathione (GSH) and without UV irradiation.

       

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