Chitosan-Cellulose Ionic Complex for Oral Drug Delivery

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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.