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首页> 外文学位 >A novel microencapsulation system: Preparation and characterization of genipin cross-linked alginate-chitosan microcapsules for live cell oral delivery and other applications.
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A novel microencapsulation system: Preparation and characterization of genipin cross-linked alginate-chitosan microcapsules for live cell oral delivery and other applications.

机译：一种新型的微囊化系统：用于活细胞口服给药和其他应用的Genipin交联海藻酸钠-壳聚糖微胶囊的制备和表征。

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摘要

Oral therapy utilizing artificial cell microencapsulation has shown promise in the treatment of many diseases. The key requirements of microcapsules for such applications include biocompatibility, mechanical stability, permeability and resistance to the human gastrointestinal (GI) environment. In particular, preservation of structural integrity is crucial when live genetically engineered cells are used. One of the main obstacles in the progress of this strategy is attaining biocompatible and stable microcapsules.; This thesis aims to develop a suitable microcapsule system, the genipin crosslinked alginate-chitosan (GCAC) microcapsule, for live cell oral delivery. The preparation procedure, including calcium-alginate ionotropic gelation, coacervative chitosan coating and covalent cross-linking by genipin, was established and optimized. Control factors affecting the formation of microcapsule membrane were identified. The structural and physical characteristics of GCAC microcapsules, such as mechanical stability, swelling characteristics, permeability, controlled release, degradation, and others were investigated and compared with earlier established microcapsule systems including alginate-chitosan and alginate-poly-L-lysine-alginate (APA). In addition, live cell oral delivery features were evaluated with a computer controlled dynamic simulated human GI model using genetically engineered Lactobacillus plantarum 80 cells as an example.; Results show that by incorporating genipin, a new class of GCAC microcapsule system can be formulated. Results also show that covalent cross-linking by genipin considerably enhanced the microcapsule stability and durability while maintaining permeability similar to that of the APA membrane. The GCAC membrane possessed strong resistance to structural degradation and GI impediments, while providing a favorable microenvironment for cell proliferation and survival in harsh GI conditions.; In addition, this research found that the fluorogenic attributes of genipin can be exploited to characterize the microcapsule membrane by confocal laser scanning microscopy. A simple, in situ, and non-destructive approach was established and extended to assess other microcapsule systems. Rapid determination of coating material distribution, binding intensity, and membrane thickness on a routine basis was achieved using this novel and superior method.; This work highlights the immense potential of the novel genipin cross-linked alginate-chitosan microcapsule as an oral delivery vehicle for live therapeutic cells and other important applications. Further studies will investigate its full potential for artificial cell oral therapy.
机译：利用人工细胞微囊的口服疗法在许多疾病的治疗中已显示出希望。对于此类应用，微胶囊的关键要求包括生物相容性，机械稳定性，渗透性和对人体胃肠道（GI）环境的抵抗力。特别地，当使用活的基因工程细胞时，保持结构完整性至关重要。该策略进展的主要障碍之一是获得生物相容性和稳定的微胶囊。本论文旨在开发一种适用于活细胞口服递送的微胶囊系统，即Genipin交联的藻酸盐-壳聚糖（GCAC）微胶囊。建立并优化了海藻酸钙离子凝胶，凝聚壳聚糖包衣和Genipin共价交联的制备方法。确定了影响微囊膜形成的控制因素。研究了GCAC微胶囊的结构和物理特性，例如机械稳定性，溶胀特性，渗透性，控释，降解等，并将其与较早建立的微胶囊体系（包括藻酸盐-壳聚糖和藻酸盐-聚-L-赖氨酸-藻酸盐）进行了比较（ APA）。此外，以转基因植物乳杆菌80细胞为例，利用计算机控制的动态模拟人胃肠道模型评估了活细胞口服递送的功能。结果表明，通过掺入京尼平，可以配制一类新的GCAC微胶囊系统。结果还表明，通过genipin进行的共价交联大大提高了微胶囊的稳定性和耐久性，同时保持了与APA膜相似的渗透性。 GCAC膜对结构降解和胃肠道障碍具有很强的抵抗力，同时为恶劣的胃肠道条件下的细胞增殖和存活提供了良好的微环境。此外，这项研究发现，可通过共聚焦激光扫描显微镜观察Genipin的荧光特性来表征微囊膜。建立了一种简单，原位，无损的方法，并将其扩展到评估其他微囊系统。使用这种新颖而优越的方法，可以常规快速测定涂料的分布，结合强度和膜厚度。这项工作突显了新型Genipin交联的藻酸盐-壳聚糖微胶囊作为活细胞治疗和其他重要应用的口服载体的巨大潜力。进一步的研究将研究其在人工细胞口服治疗中的全部潜力。

著录项

  • 作者

    Chen, Hongmei.;

  • 作者单位

    McGill University (Canada).;

  • 授予单位 McGill University (Canada).;
  • 学科 Engineering Biomedical.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 292 p.
  • 总页数 292
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;
  • 关键词

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