Chitosan-Cellulose Ionic Complex for Oral Drug Delivery

ID: MPS/DMR/BMAT(7623) 0907567 PI: Roman， Maren ORG: Virginia Tech标题：用于口服给药的壳聚糖-纤维素离子复合物知识优势：建议设计一种口服给药系统，该系统基于两种由美国食品和药物管理局监管并批准口服给药的多糖。该系统是壳聚糖（带正电的聚电解质）和纤维素纳米晶体（带负电的圆柱形巨离子）的离子配合物。壳聚糖将赋予系统生物粘附和生物吸收增强性能，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度。该研究的长期目标是开发一种治疗药物的多功能口服给药系统，该系统提供零级（恒定速率）释放，同时增强药物的毒性。S溶解度和吸收，从而提高生物利用度。具体目标是：(1)详细了解支配壳聚糖形成和性质的因素？CNC配合物，(2)表征选定的模型药物与纤维素表面的分子相互作用，(3)评估壳聚糖的载药和释放效率？(4)评估食用CNC和壳聚糖的安全性？(5)壳聚糖黏附性能的研究(6)评估壳聚糖的增透性能？体外CNC配合物。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，将聚合物化学家和分子生物学家结合起来。因此，它从这种合作产生的内在信息交流中受益。由于其口服安全性、生物相容性和环境生物降解性，所提出的药物传递系统具有高度的通用性。因此，该系统还可用于食品、化妆品、农业应用和新兴功能纺织品领域的功能分子的控制释放，仅举几例。除了技术影响外，三名研究生将在项目的跨学科环境中接受培训，最多六名本科生将接受项目培训，为他们提供暑期本科生研究经验。本科学生参与者和校内资金，以补充致力于支持本科生的NSF资金，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。

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.