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来设计新颖的材料平台，用于纳米递送系统，从而提高功能、功效和共同递送潜力的生物活性物质。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，尽管生物活性物质具有出色的健康益处，但其生物利用度和功效是当今主要关注的一些问题，主要是在营养保健品应用中。基于蛋白质的纳米载体有望提高功效和生物利用度；然而，稳定性差、负载能力差、无法共同递送以及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。拟议的计划将创新性地探索使用蛋白质-脂质缀合物来改善这些问题，并由此产生蛋白质-脂质缀合物（PLC），该缀合物将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本研究问题，这些问题将提高生物活性物质的治疗功效和生物利用度，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中设计、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，利用丰富的食品来开发 PLC。 3. 使用新技术设计基于 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-脂质缀合物纳米粒子 (hS-PLCN)，4. 确定使用体外和体内方法研究基于 PLC 的纳米载体的共同递送效率、生物利用度、功效和生物活性，以了解纳米颗粒结构和材料特性与提高生物活性的关系。将使用多种化学和物理途径，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以及使用超临界颗粒形成等新技术的hS-PLCN。该项目将是此类项目中的第一个，旨在探索 PLC 开发具有生物活性物质共同输送潜力的材料平台。该计划的成功完成将有助于推进与饮食相关的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使用这些新材料开发下一代营养保健品提供独特的机会。