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

班达拉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，通过使用常见的蛋白质和脂肪聚合物在纳米递送系统中应用来设计新的材料平台，从而提高生物活性物质的功能性、有效性和协同递送潜力。过去几年，全球蛋白质市场快速增长，加拿大正在探索通过发展附加值产业成为蛋白质行业市场领先者的机会。另一方面，尽管生物活性物质对健康有极大的好处，但生物活性物质的生物利用度和有效性是当今主要关注的问题，主要是在营养食品应用中。基于蛋白质的纳米载体在提高疗效和生物利用度方面显示出良好的前景，但是，较差的稳定性、载药量、不能共传递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-脂肪结合来改善这些问题，并由此产生的蛋白质-脂肪结合物(PLC)将用于设计具有改进功能的纳米载体。拟议的计划旨在回答有关生物聚合物系统性能的基本研究问题，这些系统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性能的材料。这一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-脂结合物(PLC)；2.采用为模型化合物开发的偶联技术，利用大量可用的食品级脂类和蛋白质开发PLC；3.利用新技术设计基于PLC的纳米载体，包括纳米乳剂、粉末状纳米乳液和中空固体蛋白质-脂结合纳米粒(HS-PLCN)；4.利用体外和体内方法测定基于PLC的纳米载体的共传递效率、生物利用度、有效性和生物活性，以了解纳米颗粒结构与材料性能之间的关系，以提高生物活性。将使用大量的化学和物理路线来创建PLC，既使用模型化合物，也使用常见的蛋白质-脂源。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的粉末纳米乳液以及使用超临界粒子形成等新技术的HS-PLCN。该计划将是第一个探索PLC来开发具有生物活性物质共同输送潜力的材料平台的项目。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努力，为加拿大蛋白质和营养食品行业提供独特的机会，将这些新材料用于开发下一代营养食品。

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.