• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文会议>World biomaterials congress >Amphiphilic core cross-linked star polymers as key building blocks of the hydrogels with hydrophobic domains for drug delivery
【24h】

Amphiphilic core cross-linked star polymers as key building blocks of the hydrogels with hydrophobic domains for drug delivery

机译：两亲核交联星形聚合物作为具有疏水域的水凝胶的关键结构单元，用于药物递送

获取原文
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Introduction: Core cross-linked star (CCS) polymers represent an intriguing platform in the application of drug delivery. CCS polymers as drug carriers are more robust to environmental variations, compared with the self-assembled micelles or vesicles, which tend to disassemble below their critical association concentration or under external stimuli, followed by an undesired burst release of drugs. Also, the ease of designing the size or functionality of arms and cores separately makes CCS polymers more attractive than other types of unimolecular containers. Like many other molecular carriers, however, the limited circulation period of CCS polymers in body would decrease the duration of drug action. In order to overcome this constraint, CCS polymers can be built into hydrogel to form a stable drug-delivery implant. Materials and Methods: In this work, CCS polymers were obtained by using ring-opening polymerization (ROP) in two steps, with firstly polyethylene glycol)-poly(E-caprolactone) (PEG-PCL) copolymers being formed as macroinitiators (MIs) and then these MIs being cross linked by [4,4'-bioxepane]-7,7'-dione (BOD) (Fig1). Various characterization tools, such as NMR, GPC, DLS, TEM, UV-Vis spectroscopy, flow cytometry and CLSM, have been adopted to investigate the structures, drug loading and release properties (pirarubicin and doxorubicin used as model hydrophobic drugs), cytotoxicity and cellular uptake of the resulting CCS polymers. Furthermore, the functionalized PEG arm was used to introduce the reactive end groups in the outer layer of the CCS, allowing for the formation of hydrogels in the presence of certain cross-linkers (Fig2). Results and Discussion: A range of CCS polymers were made with different hydrophilic/hydrophobic balance by tuning the ratio of PEG to CL and BOD blocks. These star polymers are soluble in both organic solvents and water and exist in a unimolecular state, as characterized by DLS and TEM, which provides the opportunity to easily stabilise hydrophobic drugs in aqueous environment without the need for lengthy encapsulation techniques. Their drug loading capacity is heavily influenced by the hydrophobicity and core size. The in vitro drug release study illustrated high stability of CCS-drug complex at neutral pH and a faster release profile under acidic conditions due to the degradation of pH-sensitive PCL segments. The CCS polymers also demonstrated very low toxicity, with cell viability remaining above 80% even up to high polymer concentrations. CLSM and flow cytometry analyses indicated highly efficient cellular uptake. The hydrogels based on the PEG-PCL-BOD CCS polymers feature the uniform distribution of hydrophobic domains as the hydrophobic drug depots. The swelling, mechanical and drug loading properties of the hydrogels are largely determined by the variations in hydrophobic content of the embedded CCS polymers. Conclusions: 1. A library of well-defined amphiphilic PEG-PCL-BOD CCS polymers was prepared through facile ROP. 2. They have large loading capacities for hydrophobic drugs, with the CCS-drug complex displaying high stability at neutral pH and a faster release under acidic condition. 3. The unimolecular drug containers are bio-compatible and can be internalised by cells with high efficiency. 4. The functionalized CCS polymers could become key building blocks of the hydrogels with hydrophobic domains as drug-delivery implants for cancer therapy.
机译：简介：核心交联星形（CCS）聚合物代表了药物输送应用中一个有趣的平台。与自组装的胶束或囊泡相比，CCS聚合物作为药物载体对环境变化更稳定，自组装的胶束或囊泡往往在其临界缔合浓度以下或在外部刺激下会分解，随后药物意外释放。同样，容易设计臂和芯的尺寸或功能的简便性使CCS聚合物比其他类型的单分子容器更具吸引力。但是，像许多其他分子载体一样，CCS聚合物在体内的有限循环时间将减少药物作用的持续时间。为了克服该限制，可以将CCS聚合物内置于水凝胶中以形成稳定的药物输送植入物。材料和方法：在这项工作中，通过两步使用开环聚合（ROP）获得CCS聚合物，首先形成聚乙二醇-聚（ε-己内酯）（PEG-PCL）共聚物作为大分子引发剂（MIs）然后这些MI被[4,4'-bioxepane] -7,7'-dione（BOD）交联（图1）。已经采用了各种表征工具，例如NMR，GPC，DLS，TEM，UV-Vis光谱，流式细胞仪和CLSM，来研究其结构，载药量和释放特性（用作疏水性模型药物的吡柔比星和阿霉素），细胞毒性和细胞对所得CCS聚合物的摄取。此外，功能化的PEG臂用于在CCS的外层引入反应性端基，从而在存在某些交联剂的情况下形成水凝胶（图2）。结果与讨论：通过调节PEG与CL和BOD嵌段的比例，制得了一系列具有不同亲水/疏水平衡的CCS聚合物。这些星形聚合物可溶于有机溶剂和水，并且以DLS和TEM的特征以单分子状态存在，这提供了在水性环境中轻松稳定疏水性药物的机会，而无需冗长的封装技术。它们的载药量在很大程度上受疏水性和核心尺寸的影响。体外药物释放研究表明，CCS-药物复合物在中性pH下具有很高的稳定性，而在酸性条件下由于pH敏感的PCL片段的降解，其释放速度更快。 CCS聚合物还显示出非常低的毒性，甚至在高聚合物浓度下，细胞活力也保持在80％以上。 CLSM和流式细胞仪分析表明高效的细胞摄取。基于PEG-PCL-BOD CCS聚合物的水凝胶具有疏水性结构域作为疏水性药物贮库的均匀分布。水凝胶的溶胀，机械和药物负载特性在很大程度上取决于包埋的CCS聚合物疏水含量的变化。结论：1.通过简便的ROP制备了定义明确的两亲性PEG-PCL-BOD CCS聚合物文库。 2.它们对疏水性药物具有较大的负载能力，CCS-药物复合物在中性pH下显示出高稳定性，在酸性条件下释放更快。 3.单分子药物容器具有生物相容性，可以被细胞高效内化。 4.功能化的CCS聚合物可以成为具有疏水域的水凝胶的重要组成部分，作为癌症治疗的药物递送植入物。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号