Innovations in protein-lipid conjugation and novel technologies for developing protein-based nanodelivery systems to improve the delivery mechanism, efficacy, and bioavailability of bioactives

蛋白质-脂质结合的创新和开发基于蛋白质的纳米递送系统的新技术，以改善生物活性物质的递送机制、功效和生物利用度

• 批准号: RGPIN-2020-07136
• 负责人: Bandara, Nandika
• 金额: $ 1.75万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763595
• 关键词: Innovations; protein; lipid; conjugation; novel

The overall vision of Dr. Bandara's proposed research program is to use nanotechnology, material science, and chemistry principles to design novel material platforms by using commonly available protein and lipid polymers for applications in nanodelivery systems with improved functionality, efficacy, and co-delivery potential of bioactives. The global protein market is experiencing rapid growth over the past years, and Canada is exploring the opportunities to become a market leader in protein industry by developing value-added industries. On the other hand, irrespective of their excellent health benefits, bioavailability & efficacy of bioactives are some of the primary concerns nowadays, mainly in nutraceutical applications. Protein-based nanocarriers show promise in improving efficacy and bioavailability; however, poor stability, loading capacity, inability of co-delivery and susceptibility to gastric digestion limits the effective utilization of protein-based nanocarriers. The proposed program will innovatively explore the use protein-lipid conjugation to improve those issues and resulting protein-lipid conjugates (PLC) that will be used for designing nanocarriers with improved functionality. The proposed program is designed to answer fundamental research questions about the properties of biopolymer systems that will improve the therapeutic efficacy & bioavailability of the bioactives, and how to design materials with required properties. The short-term objectives of this discovery program are to 1. Design, fabricate & characterize protein-lipid conjugates (PLC) from model fatty acids and proteins, 2. Adopt the conjugation techniques developed for model compounds to develop PLC using abundantly available food-grade lipids and proteins 3. Engineering PLC-based nanocarriers, including nanoemulsions, powdered nanoemulsions, and hollow solid protein-lipid conjugate nanoparticles (hS-PLCN) using novel techniques and 4. Determine co-delivery efficiency, bioavailability, efficacy, and bioactivity of the PLC-based nanocarriers using in-vitro and in-vivo methods to understand the relationship of nanoparticle structure and material properties on improving bioactivity. A wide array of chemical and physical routes will be used in creating PLC using both model compounds and common protein-lipid sources. The developed PLC will be used for creating a range of nanocarrier systems including nanoemulsions, powdered nanoemulsions via supercritical CO2 assisted drying and hS-PLCN using novel technologies such as supercritical particle formation. This program will be the first of this kind in exploring PLC for developing material platforms with co-delivery potential for bioactives. Successful completion of this program will help to advance the research and commercialization efforts of diet-related bioactives, provide unique opportunities for Canadian protein and nutraceutical industries to use these novel materials for developing next-generation nutraceuticals.

Bandara博士提出的研究计划的总体愿景是使用纳米技术，材料科学和化学原理，通过使用常见的蛋白质和脂质聚合物在具有改善功能，功效和共同交付潜能改善的纳米传递系统中应用，以设计新型材料平台。生物活性剂。在过去的几年中，全球蛋白质市场正在迅速增长，加拿大正在通过发展增值行业探索成为蛋白质行业市场领导者的机会。另一方面，无论其出色的健康益处，生物活性剂的生物利用度和功效如何，都是当今的一些主要问题，主要是在营养应用中。基于蛋白质的纳米载体在提高功效和生物利用度方面表现出了希望。然而，稳定性差，负载能力，无能为力和对胃消化的敏感性限制了基于蛋白质的纳米载体的有效利用。拟议的程序将创新探索使用蛋白 - 脂质偶联以改善这些问题并导致蛋白质 - 脂质结合物（PLC），该蛋白质偶联物（PLC）将用于设计具有改善功能的纳米载体。该计划旨在回答有关生物聚合物系统特性的基本研究问题，这些问题将改善生物活性剂的治疗功效和生物利用度，以及如何使用所需特性设计材料。该发现程序的短期目标是1。设计，制造和表征来自模型脂肪酸和蛋白质的蛋白质 - 脂质结合物（PLC），2。采用用于模型化合物开发的共轭技术，以使用丰富的可用食物开发PLC等级脂质和蛋白质3。基于工程PLC的纳米载极，包括纳米乳液，粉末状纳米乳液和空心的固体蛋白蛋白 - 蛋白 - 蛋白 - 含量偶联纳米颗粒（HS-PLCN），并使用新技术和4。基于PLC的纳米载体使用体外和体内方法了解纳米颗粒结构与材料特性在改善生物活性方面的关系。多种化学和物理路线将用于使用模型化合物和常见蛋白质脂质源创建PLC。开发的PLC将用于创建一系列纳米载体系统，包括纳米乳液，通过超临界二氧化碳辅助干燥粉末的纳米乳液和使用新型技术（例如超临界颗粒形成）。该计划将是探索PLC的第一个，用于开发具有生物活性剂潜力的材料平台。该计划的成功完成将有助于促进与饮食相关的生物活性剂的研究和商业化工作，为加拿大蛋白质和营养行业提供独特的机会，以使用这些新型材料来开发下一代营养素。