Nanoencapsulation of therapeutic peptides in smart environmentally responsive biopolymers

我的研究针对的是通过包埋生物制品来固定化，包括活细胞、酶和其他生物活性物质，如DNA和治疗性多肽。其目的是将生物材料包装在称为微球或微胶囊的小球形颗粒或凝胶中。颗粒提供保护环境，使治疗和其他应用的保留、稳定和/或受控输送成为可能。微胶囊方案被设计成形成微米尺寸(大约50微米到1毫米直径)的包覆或未包覆的颗粒和凝胶，其中包含生物活性材料。这项提案中概述的研究目的是将颗粒尺寸扩展到纳米级，从150纳米到几微米。包括胰岛素和人血管内皮生长因子在内的治疗性多肽将被检测为纳米胶囊和受控释放。这种纳米粒子将被设计成对环境敏感的“智能”凝胶，因为它们会对环境触发因素(如pH值的变化)做出反应而膨胀或收缩。根据预期的治疗应用，这种反应行为对于大蛋白/多肽和小蛋白/多肽的负载和保留以及多肽的受控或触发释放都很重要。这项研究为培训高素质人才提供了极好的机会，因为它是多学科的，横跨化学、生物化学和生物医学工程领域，重点是生物聚合物材料、生物技术和纳米技术，并通过实验方法和仪器得到支持。制药、生物技术产品、生物医学设备、先进材料、纳米产品和纳米技术领域正在迅速增长，并在最近的重新分配工作中被确定为战略优先事项。口服胰岛素等基于蛋白质的药物将是一项重大突破，将取决于所有这些领域的研究、培训和专业知识。

My research is directed toward the immobilization via entrapment of biologicals, including living cells, enzymes and other biologically active materials such as DNA and therapeutic peptides. The intent is to package the biological material, typically within small spherical particles or gels, termed microspheres or microcapsules. The particles provide a protective environment, enabling retention, stabilization, and/or controlled delivery for therapeutic and other applications. Microencapsulation protocols are designed to form micron-sized (approximately 50 microns to 1 mm diameter) coated or uncoated particles and gels, containing the bioactive material. The intent of the research outlined in this proposal is to extend the particle size into the nano-scale, from 150 nm to a few microns in diameter. Therapeutic peptides will be examined for nanoencapsulation and controlled delivery including insulin and human vascular endothelial growth factor. The nanoparticles will be designed to be environmentally responsive, "smart" gels in that they will swell or contract in response to environmental triggers such as a change in pH. This responsive behavior will be important for the loading and retention of large and small proteins/peptides respectively, and for controlled or triggered release of the peptide, depending on the intended therapeutic application. This research provides a wonderful opportunity for the training of highly qualified personnel, since it is multi-disciplinary, spanning the fields of chemical, biochemical and biomedical engineering, with a strong emphasis on biopolymeric materials, biotechnology and nanotechnology, supported through experimental methods and instrumentation. The fields of pharmaceuticals, biotech products, biomedical devices, advanced materials, nanoproducts and nanotechnologies are growing rapidly and are identified as strategic priorities in the most recent reallocation exercise. Oral administration of a protein-based drug such as insulin would be an important breakthrough, and will depend on research, training and expertise in all of these fields.