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

该项目的研究目标是：(1)深入了解胃肠道（GI）环境中控制乳剂功能的物理现象和理化参数；(2)建立计算模型来预测乳剂对口服化合物吸收的影响。文献中有许多研究报告了通过特定乳剂配方增强药物溶解度和/或口服生物利用度的研究。本文提出的方法是将乳剂在胃肠道中的整体功能分解为多个组成过程，并使用一套全面的乳剂配方来研究这些过程，这些配方通过统计学设计来测试可能的物理和化学性质范围（油结构、表面活性剂亲水-亲脂平衡、药物logP等）。乳剂功能在胃肠道环境中的关键机制过程将在体外模拟。具体而言，将测量在混合胃肠道环境中形成乳化液的能力以及药物释放、乳化液消化和肠道通透性增强的动力学，并将其与制剂的理化性质相关。适当的动力学表达式和动力学参数对配方性质的依赖将被整合到一个基于系统的模型中。该模型预测乳剂对药物吸收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服化合物吸收的能力将对社会健康产生重大影响。合理的乳剂设计将实现该技术的潜力，使口服给药成为不可行的产品，并将深入了解“食物效应”，这是一种影响大多数药物口服生物利用度的鲜为人知的现象。与研究活动高度结合的是注重实践教育的多层次教育计划。具体而言，本研究提供了一个全新的以行业为指导，以问题为基础的药物给药工程分析课程，作为一个以实践为导向的课程模式。作为这一努力的一部分，其他学院将建立必要的合作机制，以设计类似的课程。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经历和本科生的学术经历。最后，未来的研究人员将通过广泛的高中参与研究和“建立桥梁”高中推广计划，接触到工程的兴奋。Semahat Demir博士，生物医学工程项目主任

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