Stabilization of therapeutic microbes for inclusion in a liquid matrix for delivery to the intestines

稳定治疗微生物以包含在液体基质中以输送到肠道

• 批准号: 10603190
• 负责人: Aaron C Anselmo
• 金额: $ 29.59万
• 依托单位: VITAKEY, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603190
• 关键词: Acids; Adhesions; Alginates; Biopolymers; Carbohydrates; Carbon Dioxide; Cells; Chitosan; Clinical Research; Colloids; Colon; Complex; Critical Illness; Deglutition Disorders; Deposition; Desire for food; Dextrans; Diarrhea; Digestion; Drug Delivery Systems; Dryness; Eating; Elderly; Electrostatics; Emulsions; Encapsulated; Ensure; Enteral Feeding; Environment; Evaluation; Excipients; Fatty acid glycerol esters; Formulation; Gastrointestinal tract structure; Glycerol; Government; Growth; Health; Home; Hospitalization; Hospitals; Immune system; Immunity; Immunologics; Intestines; Inulin; Investigation; Lactobacillus casei rhamnosus; Length of Stay; Life; Liquid substance; Malignant Neoplasms; Marketing; Medical; Microbe; Micronutrients; Modernization; Nursing Homes; Nutrient; Nutritional; Oral; Oral Administration; Oxygen; Patients; Performance; Persons; Phase; Polysaccharides; Powder dose form; Probiotics; Procedures; Proteins; Recovery; Reporting; Risk; Sedimentation process; Sodium Chloride; Sterilization; Stomach; Stroke; Surface; System; Tannic Acid; Techniques; Technology; Temperature; Therapeutic; Time; Ventilator; Volatile Fatty Acids; Water; absorption; antimicrobial; beeswax; bile salts; cost; dietary supplements; disability; enteric pathogen; experience; gut colonization; gut health; gut microbiota; hazard; improved; intestinal barrier; liquid formulation; manufacture; microorganism; nutrient absorption; nutrition; pasteurization; prevent; probiotic therapy; reconstitution; sugar; technology platform

Project Summary/Abstract Enteral feeding (EF) is an essential medical procedure used to supply nutrients directly to the gastrointestinal (GI) tract of patients who are unable to eat independently. EF formula is often purchased as a ready-to-use liquid that contains carbohydrates, protein, fats, and micronutrients to ensure adequate nutritional benefit for the patient. The addition of therapeutic probiotics to EF formula has been shown to improve patient health and recovery, while reducing the cost burden to patients and hospitals. However, specific challenges remain which have prevented widespread use. These include: an instability of probiotics in nutrient rich, complex liquid mediums, including high fat, salt, or sugar liquids and biphasic systems such as emulsions and collo ids, a narrow list of compatible probiotics with marginal therapeutic benefit, a risk of cross-contamination during handling/reconstitution of powder probiotics, sedimentation/aggregation of probiotics, causing blockage of the feeding tube, inactivation of the probiotics by the acidic stomach environment, and a lack of proper adhesion and growth in the gastrointestinal tract. A platform drug delivery technology which encapsulates cells and stabilizes the compounds during storage and digestion while facilitating both mucoadhesion and direct growth on intestinal surfaces has previously been developed and will be optimized for use in liquid EF nutritional formula in this proposal. Lactobacillus rhamnosus HN001, a microbe reported to support gut health and the immune system, will be coated with the platform technology and evaluated for performance and shelf life stability in a complex liquid EF formula. Furthermore, multiple excipients with moisture barrier features will be explored in an effort to extend the liquid shelf life stability.

项目总结/摘要 肠内喂养（EF）是一种基本的医疗程序，用于直接向患者提供营养。 不能独立进食的患者的胃肠道（GI）。EF公式通常 作为含有碳水化合物、蛋白质、脂肪和微量营养素的即用型液体购买 以确保患者获得足够的营养益处。添加治疗性益生菌， EF配方已被证明可以改善患者的健康和恢复，同时降低成本 给患者和医院带来负担。然而，具体的挑战依然存在， 广泛使用。其中包括： 益生菌在营养丰富的复杂液体培养基中的不稳定性，包括 高脂肪、盐或糖液体和双相体系如乳液， 胶体， 具有边际治疗益处的相容益生菌的狭窄列表， 在粉末益生菌的处理/重构过程中存在交叉污染的风险， 益生菌的沉降/聚集，导致饲管堵塞， 通过酸性胃环境使益生菌失活，和 在胃肠道中缺乏适当的粘附和生长。 一种包封细胞并稳定化合物的平台药物递送技术 在储存和消化过程中，同时促进粘膜粘附和在肠粘膜上的直接生长， 表面以前已经开发，并将优化用于液体EF营养 在这个提案中。Lactobacillus rhamnosus HN 001，一种支持肠道的微生物 健康和免疫系统，将被涂上平台技术和评估， 在复杂的液体EF配方中的性能和保质期稳定性。此外，多个 将探索具有防潮功能的赋形剂，以努力延长液体货架期 生活稳定。