Transport of Nanomedicine in the Environment

最近的研究估计，200多种基于纳米技术的药物和给药系统已进入临床前、临床或商业开发，40多种纳米药物产品已投放市场，2011年纳米药物销售额估计已达200亿美元。随着纳米药物的消费和生产日益增加，人们越来越认识到纳米药物在环境中的发生和去向以及对人类健康的潜在后果。目前，填充治疗剂的聚合物纳米微粒药物传递系统(PNDDS)是最常用的纳米药物形式之一，因为它能够溶解水不溶分子，并且具有更高的负载能力、更长的血液循环时间和在水介质中良好的结构稳定性。虽然PNDDS的这些特性在制药科学方面是有益的，但与环境科学相比可能是有害的，因为它促进了潜在生态危害的运输。因此，拟议工作的主要目标是更好地了解PNDDS在环境中的传输现象。智力优点：拟议的活动主要寻求确定纳米药物在环境中传输过程中发生的扩散、对流、吸附、释放和降解过程的相对重要性。这项工作的另一个基本问题是确定这些过程如何不仅取决于纳米药物和所涉及的环境表面的结构和物理化学性质，而且还取决于环境条件，如pH和温度。工作假说是，纳米药物在环境中的传输受到纳米药物性质(如尺寸和化学功能化)以及环境条件(如流速、温度、粗糙度和环境表面化学)的协同组合的调节。这一假设将通过使用模拟环境表面的石英晶体微天平研究来验证，如二氧化硅、方解石和纤维素，以及具有不同尺寸、电荷、组成、负载特性和功能的各种类型的纳米药物。生成的数据将用环境运输模型进行描述。PI在表面和界面科学、纳米技术和药物输送领域的独特专业知识组合使他能够产生有希望的初步结果，支持该项目的工作假说，并将使他能够成功地管理这项工作。总而言之，从工程科学的角度来看，拟议的活动具有重要意义，因为它将促进对水环境中纳米颗粒在吸附表面附近传输的了解和理解。这些知识对于正确评估纳米药物的分布和命运以及制定成功的战略以最大限度地减少其在环境中的扩散至关重要。该项目的成果还有望惠及其他领域和应用，依赖于控制纳米颗粒和生物制品的吸附，如过滤、静电印刷、蛋白质和细胞分离，以及食品乳液和泡沫稳定。广泛影响：拟议的工作包括三个组成部分，用于整合研究和教育。第一个组成部分努力增加任职人数不足的学生对学术研究的参与，第二个组成部分涉及课程开发，第三个组成部分涉及培训能够在学术或工业研究岗位上成功担任独立调查人员的研究生。PI积极参与指导一个与拟议工作直接相关的项目中任职人数不足的本科生。通过这个项目，我们的目标是招收和培训更多少数族裔和代表性不足的研究生和本科生，并向公众传授纳米技术的环境方面的知识。该项目还将为研究生提供环境科学、化学工程和纳米技术方面的多学科培训。这项工作将通过在非正式的公共科学讲座、会议和部门研讨会上由PI和学生发表演讲来广泛传播。

1236532AkbulutRecent studies have estimated that more than 200 nanotechnology-based drugs and delivery systems have entered pre-clinical, clinical, or commercial development and over 40 nanomedicine products have been on the market, with nanomedicine sales estimated to have reached 20 billion dollars in 2011. With the increasing consumption and production of nanomedicine, the occurrence and fate of nanomedicine in the environment as well as the potential consequences for human health have been increasingly recognized. Currently, polymeric nanoparticulate drug delivery system (PNDDS) filled with therapeutic agents represents the one of the most commonly used forms of nanomedicine due to their ability to solubilize water-insoluble molecules as well as their higher payload capacity, extended blood circulation times, and excellent structural stability in aqueous media. While these properties of PNDDS are beneficial in terms of pharmaceutical science, it can be detrimental from that of environmental science, as it facilitates the transport of potential ecological hazards. The main objective of the proposed work is thus obtaining a better understanding of the transport phenomena of PNDDS in the environment.Intellectual Merit: The proposed activity primarily seeks to determine the relative importance of the diffusion, convection, adsorption, release, and degradation processes taking place during the transport of nanomedicine in the environment. Another fundamental issue in this work is determining how these processes depend not only upon the structural and physicochemical properties of the nanomedicine and the environmental surfaces involved but also upon environmental conditions such as pH and temperature. The working hypothesis is that the transport of nanomedicine in the environment is modulated by a synergistic combination of nanomedicine properties such as size and chemical functionalization as well as environmental conditions such as flow rates, temperature, roughness, and the chemistry of environmental surfaces. The hypothesis will be tested through quartz crystal microbalance studies using model environmental surfaces such as silica, calcite, and cellulose, as well as various types of nanomedicine with different sizes, charges, compositions, loading properties, and functionalities. The generated data will be described with environmental transport models. The PI's unique combination of expertise in surface and interface science, nanotechnology, and the drug delivery area has enabled him to generate promising preliminary results in the support of the project's working hypothesis and will allow him to successfully manage this work. Overall, the proposed activity is significant from an engineering science perspective, as it will advance knowledge and understanding of nanoparticle transport near adsorptive surfaces in aqueous environments. Such knowledge is critical to properly assess the distribution and fate of nanomedicine and to develop successful strategies for minimizing its dispersal in the environment. The outcomes of this project are also anticipated to benefit other fields and applications relying on controlling the adsorption of nanoparticles and bioparticles such as filtration, xerography, protein and cell separation, as well as food emulsion and foam stabilization.Broader Impact: The proposed work has three components for integrating research and education. The first component strives to increase the participation of underrepresented students in academic research, the second concerns curriculum development, and the third involves training graduate students who are capable of functioning successfully as independent investigators in academic or industrial research positions. The PI is actively involved in mentoring underrepresented undergraduate students in a project that is directly related to the proposed work. Through this project, we aim to recruit and train more minority and underrepresented graduate and undergraduate students and to teach the general public about the environmental aspects of nanotechnology. This project will also provide graduate students with multidisciplinary training in environmental science, chemical engineering, and nanotechnology. The work will be broadly disseminated through presentations by the PI and students at informal public science talks, conferences, and departmental seminars.