EFFECT OF STRUCTURE AND SURFACE PROPERTIES OF NANODIAMONDS ON DRUG DELIVERY

纳米金刚石的结构和表面性质对药物输送的影响

• 批准号: 8171792
• 负责人: ALBERT TO
• 金额: $ 0.14万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171792
• 关键词: Adsorption; Antineoplastic Agents; Area; Carbonates; Computer Retrieval of Information on Scientific Projects Database; Devices; Diffusion; Dissociation; Doxorubicin; Doxorubicin Hydrochloride; Drug Delivery Systems; Drug Formulations; Funding; Grant; Institution; Mechanics; Mediating; Medicine; Modeling; Molecular; Outcomes Research; Paclitaxel; Pharmaceutical Preparations; Pharmacy (field); Process; Property; Research; Research Personnel; Resources; Role; Route; Solubility; Solvents; Source; Structure; Surface; Surface Properties; Technology; Therapeutic; Therapeutic Effect; United States National Institutes of Health; Vinblastine; aqueous; density; dosage; interest; self assembly; simulation; small molecule

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Drug delivery technology is a vital ingredient of medicine in order to achieve the desired therapeutic effects. Typically this issue is scrutinized in connection with the pharmaceutics research determining drug dosage, formulation and administrative route. Currently, many of small molecule drugs are not utilized to their full therapeutic potential due to poor aqueous solubility or inadequate delivery properties. Anti-cancer agents such as vinblastine, doxorubicin and taxol may be cited as good examples of such cases. To overcome these shortcomings, we propose the chemo-mechanical property modeling of a transformational device for a nanodiamond-mediated localized delivery of a model chemotherapeutic, Doxorubicin hydrochloride (Dox). Of particular interest is the prediction of the unknown structure and surface properties of nanodiamonds funtionalized with carboxyl and carbonated molecules for drug adsorption. The configuration of the functionalized nanodiamonds will be first predicted by first-principles calculations. Then a molecular level MC simulation is performed to predict the self-assembly process and aggregate configuration of the NDs and the drug (ie. Dox). The dissociation of the drugs from the nanodiamonds and the subsequent diffusion through the paralyne will be modeled by MD simulations. Continuum scale diffusion parameters can be extracted from the molecular level simulations to perform more macroscopic-scale simulation of diffusion of drugs originating from the device to a target area. A number of material parameters will be studied to understand their effect on the drug loading and drug release rate. They include the size distribution of the NDs, the density of the functionalized groups on the ND surface, the pH of the solvent, initial density of the drugs, etc. The outcome of this research will enable us to understand the structure and surface properties of NDs and their role in drug delivery.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 药物输送技术是医学的重要成分，以实现所需的治疗作用。通常，该问题与确定药物剂量，配方和行政途径的药物研究有关。目前，由于水溶性差或递送特性不足，许多小分子药物没有用于其全部治疗潜力。抗癌剂，例如vinblastine，阿霉素和紫杉醇可能被认为是这种情况的很好的例子。为了克服这些缺点，我们提出了转化设备的化学机械性能建模，用于用于模型化学治疗性盐酸阿霉素（DOX）的纳米座介导的局部递送。特别令人感兴趣的是用羧基和碳化分子促进药物吸附的纳米座的未知结构和表面特性的预测。官能化的纳米原子座的配置将首先通过第一原理计算预测。然后，进行分子水平MC模拟，以预测NDS和药物的自组装过程和汇总构型（即DOX）。药物从纳米符号的解离以及随后通过帕拉利因的扩散将通过MD模拟建模。可以从分子水平模拟中提取连续尺度扩散参数，以对源自设备到目标区域的药物的扩散进行更多的宏观尺度模拟。将研究许多材料参数，以了解它们对药物加载和药物释放率的影响。它们包括ND的尺寸分布，ND表面上功能化基团的密度，溶剂的pH值，药物的初始密度等。这项研究的结果将使我们能够了解NDS的结构和表面特性及其在药物输送中的作用。