Chitosan-Cellulose Ionic Complex for Oral Drug Delivery

用于口服药物递送的壳聚糖-纤维素离子复合物

• 批准号: 0907567
• 负责人: Maren Roman
• 金额: $ 40.5万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0907567&HistoricalAwards=false
• 关键词: Chitosan; Cellulose; Ionic; Complex; Oral

ID: MPS/DMR/BMAT(7623) 0907567 PI: Roman, Maren ORG: Virginia Tech Title: Chitosan-Cellulose Ionic Complex for Oral Drug DeliveryINTELLECTUAL MERIT: It is proposed to devise an oral drug delivery system, based on two polysaccharides that are regulated by the U.S. Food and Drug Administration and approved for oral administration. The proposed system is an ionic complex of chitosan, a positively charged polyelectrolyte, and cellulose nanocrystals, negatively charged, cylindrical macroions. Chitosan will impart to the system bioadhesive and bioabsorption-enhancing properties, whereas the cellulose nanocrystals (CNCs) will bind poorly soluble therapeutic molecules via surface complexation, thus preventing undesirable crystallization, and control their release rate through desorption. The long-term goal of the proposed research is a multifunctional oral delivery system for therapeutic agents that provides zero-order (constant rate) release while simultaneously enhancing the agent?s solubility and absorption and, thus, bioavailability. The specific objectives are: (1) Develop a detailed understanding of the factors governing the formation and properties of chitosan?CNC complexes, (2) Characterize the molecular interactions of selected model drugs with a cellulose surface, (3) Assess the drug loading and release efficiencies of chitosan?CNC complexes, (4) Assess the safety of ingestion of CNCs and chitosan?CNC complexes in vitro, (5) Assess the mucoadhesive properties of chitosan?CNC complexes in vitro, and (6) Assess the permeability-enhancing properties of chitosan?CNC complexes in vitro. The project will employ physicochemical and microscopy methods to study the formation and properties of the ionic complex and its interactions with and release of model drugs. Cell culture studies will be used to assess the toxicity of the ionic complex to human intestinal epithelial cells and the complexes effectiveness to enhance drug permeability.BROADER IMPACTS: The proposal is inherently interdisciplinary, pairing a polymer chemist and molecular biologist. It thus benefits from the intrinsic information exchange arising from such collaborations. The proposed drug delivery system is highly versatile by reason of its oral safety, biocompatibility, and environmental biodegradability. As a result, the system could also be used for controlled release of functional molecules in foodstuffs, cosmetics, agricultural applications, and applications in the emerging field of functional textiles, to name a few. In addition to the technological impact, three graduate students will be trained in the interdisciplinary environment of the project and up to six undergraduate students will be trained on the project by providing them with summer undergraduate research experience. Undergraduate student participants, and intramural funding to supplement the NSF funding committed to support undergraduates, will be sought through the Virginia Tech Multicultural Academic Opportunities Program and an existing Virginia Tech REU program.

ID：MPS/DMR/BMAT(7623) 0907567 PI：Roman，Maren ORG：弗吉尼亚理工大学 标题：用于口服药物递送的壳聚糖-纤维素离子复合物 智力优点：建议设计一种基于两种受美国食品和药物管理局监管并批准用于口服给药的多糖的口服药物递送系统。所提出的系统是壳聚糖（一种带正电的聚电解质）和纤维素纳米晶体（带负电的圆柱形大离子）的离子复合物。壳聚糖将赋予系统生物粘附和生物吸收增强特性，而纤维素纳米晶体（CNC）将通过表面络合结合难溶性治疗分子，从而防止不良结晶，并通过解吸控制其释放速率。拟议研究的长期目标是一种用于治疗药物的多功能口服递送系统，该系统提供零级（恒定速率）释放，同时增强药物的溶解度和吸收，从而提高生物利用度。具体目标是：（1）详细了解控制壳聚糖？CNC复合物的形成和性质的因素，（2）表征选定模型药物与纤维素表面的分子相互作用，（3）评估壳聚糖？CNC复合物的药物装载和释放效率，（4）评估体外摄入CNC和壳聚糖？CNC复合物的安全性， (5)评估壳聚糖·CNC复合物的体外粘膜粘附特性，以及(6)评估壳聚糖·CNC复合物的体外通透性增强特性。 该项目将采用物理化学和显微镜方法来研究离子复合物的形成和性质及其与模型药物的相互作用和释放。细胞培养研究将用于评估离子复合物对人肠上皮细胞的毒性以及复合物增强药物渗透性的有效性。更广泛的影响：该提案本质上是跨学科的，由高分子化学家和分子生物学家配对。 因此，它受益于此类合作所产生的内在信息交换。 所提出的药物递送系统由于其口服安全性、生物相容性和环境生物降解性而具有高度通用性。因此，该系统还可用于食品、化妆品、农业应用以及新兴功能性纺织品领域的应用等功能性分子的控制释放。 除了技术影响外，三名研究生将在该项目的跨学科环境中接受培训，最多六名本科生将通过为他们提供暑期本科研究经验来接受该项目的培训。 将通过弗吉尼亚理工大学多元文化学术机会计划和现有的弗吉尼亚理工大学 REU 计划寻求本科生参与者以及校内资金来补充致力于支持本科生的 NSF 资金。