CAREER: Mechanistic Studies and Modeling of Self-Emulsifying Drug Delivery Systems

该项目的研究目标是：(1)深入了解乳剂在胃肠道(GI)环境中的物理现象和控制作用的物理化学参数，(2)开发一个计算模型来预测乳剂对口服化合物吸收的影响。有许多文献报道，通过特定的乳剂制剂，可以提高药物的溶解度和/或口服生物利用度。建议的方法是将乳剂在胃肠道中的整体功能分解为组成过程，并使用一套全面的乳剂配方来研究这些过程，这些乳剂配方的统计设计旨在测试可能的物理和化学性质范围(油结构、表面活性剂亲水性-亲脂性平衡、药物对数等)。将在体外模拟GI环境中乳剂作用的关键机制过程。具体地说，将测量在混合GI环境中形成乳剂的能力以及药物释放、乳剂消化和增强肠道通透性的动力学，并与制剂的物理化学性质相关。然后，将适当的动力学表达式和动力学参数对配方性质的依赖关系整合到基于系统的模型中。该模型预测乳剂对药物吸收的影响的能力将通过体外和体内实验进行验证。预测乳剂何时以及如何影响口腔化合物吸收的能力将对社会健康产生重大影响。合理的乳剂设计将认识到这项技术的潜力，以口服方式提供药物，否则可能是不可行的产品，并将深入了解“食物效应”，一种鲜为人知的现象，影响大多数药物的口服生物利用度。与研究活动高度结合的是注重实践导向教育的多层次教育计划。具体地说，本研究为一种新颖的行业指导、基于问题的药物传递工程分析课程作为一种以实践为导向的课程模式提供了教育材料。作为这项努力的一部分，将建立让其他教员开展设计类似课程所需的合作的机制。此外，东北大学的合作教育模式将扩大到包括研究生的工业和本科学术经验。最后，未来的研究人员将通过广泛的高中参与研究和高中推广计划接触到工程学的兴奋。Semahat Demir，博士项目主任，生物医学工程

CBET-0748048, CarrierThe research objectives of the project are: (1) to develop insight into the physical phenomena and physicochemical parameters governing emulsion function in the gastrointestinal (GI) environment, and (2) develop a computational model to predict the influence of emulsions on oral compound absorption. There are many studies in the literature reporting enhancement in drug solubility and/or oral bioavailability by specific emulsion formulations. The proposed approach is to break down the overall function of emulsions in the GI tract into comprising processes and study these processes using a comprehensive set of emulsion formulations statistically designed to test the possible range of physical and chemical properties (oil structure, surfactant hydrophilic-lipophilic balance, drug logP, etc.). Key mechanistic processes of emulsion function in the GI environment will be simulated in vitro. Specifically, the ability to form an emulsion in the mixed GI environment and kinetics of drug release, emulsion digestion, and intestinal permeability enhancement will be measured and related to formulation physicochemical properties. Appropriate kinetic expressions and dependence of kinetic parameters on formulation properties will then be integrated into a systems-based model. The ability of the model to predict the influence of emulsions on drug absorption will be validated using in vitro and in vivo experiments. The ability to predict when and how emulsions influence oral compound absorption will have a significant impact on societal health. Rational emulsion design will realize the potential of this technology to orally deliver drugs that may otherwise not be viable products, and insight will be gained into the 'food effect', a poorly understood phenomenon that influences the oral bioavailability of most drugs. Highly integrated with the research activities is a multi-tiered educational plan focused on practice-oriented education. Specifically, the research provides educational substance for a novel industry-mentored, problem-based Engineering Analysis of Drug Delivery course to serve as a practice-oriented course model. Mechanisms for other faculty to develop the collaborations necessary to design similar courses will be established as part of this effort. In addition, the cooperative education model at Northeastern University will be expanded to include graduate industrial and undergraduate academic experiences. Finally, tomorrow's researchers will be exposed to the excitement of engineering through extensive high school involvement in research and the 'Building Bridges' high school outreach program. Semahat Demir, Ph.D.Program DirectorBiomedical Engineering