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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=718490
• 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利用纳米技术，材料科学和化学原理，通过使用常用的蛋白质和脂质聚合物设计新型材料平台，用于纳米递送系统，改善功能，功效和生物活性物质的共同递送潜力。全球蛋白质市场在过去几年中经历了快速增长，加拿大正在探索通过发展增值产业成为蛋白质行业市场领导者的机会。另一方面，尽管它们具有优异的健康益处，生物活性物质的生物利用度和功效是当今的一些主要关注点，主要是在营养药物应用中。基于蛋白质的纳米载体在改善功效和生物利用度方面显示出前景;然而，差的稳定性、负载能力、不能共递送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。该计划将创新性地探索使用蛋白质-脂质缀合来改善这些问题，并产生蛋白质-脂质缀合物（PLC），用于设计具有改进功能的纳米载体。该计划旨在回答有关生物聚合物系统特性的基础研究问题，这些特性将提高生物活性物质的治疗效果和生物利用度，以及如何设计具有所需特性的材料。该发现计划的短期目标是1。从模型脂肪酸和蛋白质设计、制造和表征蛋白质-脂质缀合物（PLC），2.采用为模型化合物开发的缀合技术，使用丰富的食品级脂质和蛋白质开发PLC 3。使用新技术工程化基于PLC的纳米载体，包括纳米乳液、粉末状纳米乳液和中空固体蛋白质-脂质缀合物纳米颗粒（hS-PLCN）;和4.使用体外和体内方法确定基于PLC的纳米载体的共递送效率、生物利用度、功效和生物活性，以了解纳米颗粒结构和材料性质对改善生物活性的关系。广泛的化学和物理途径将用于使用模型化合物和常见的蛋白质-脂质来源来创建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CO2辅助干燥的粉末纳米乳液和使用超临界颗粒形成等新技术的hS-PLCN。该计划将是探索PLC开发具有生物活性物质共同交付潜力的材料平台的第一个此类计划。该计划的成功完成将有助于推进饮食相关生物活性物质的研究和商业化工作，为加拿大蛋白质和营养保健品行业提供独特的机会，利用这些新材料开发下一代营养保健品。