EFFECT OF STRUCTURE AND SURFACE PROPERTIES OF NANODIAMONDS ON DRUG DELIVERY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 药物输送技术是医学达到预期治疗效果的重要组成部分。通常，这一问题与确定药物剂量、配方和给药路线的药剂学研究有关。目前，许多小分子药物由于水溶性差或给药性能不佳而没有充分发挥其治疗潜力。长春花碱、阿霉素和紫杉醇等抗癌药物就是很好的例子。为了克服这些缺点，我们提出了一种用于纳米钻石介导的局部递送模型化疗药物盐酸阿霉素(Dox)的转化装置的化学机械特性建模。特别令人感兴趣的是预测用于药物吸附的羧基和碳酸盐分子功能化的纳米钻石的未知结构和表面性质。首先通过第一性原理计算来预测功能化纳米金刚石的构型。然后进行分子水平的MC模拟来预测NDS和药物的自组装过程和聚集结构(即。DOX)。药物从纳米钻石上的解离和随后通过瘫痪的扩散将由分子动力学模拟来模拟。可以从分子水平的模拟中提取连续尺度的扩散参数，以对源自该装置的药物向目标区域的扩散进行更宏观的模拟。将研究一些材料参数，以了解它们对载药量和药物释放速率的影响。它们包括NDS的尺寸分布、ND表面官能团的密度、溶剂的pH值、药物的初始密度等。本研究的结果将使我们能够了解NDS的结构和表面性质以及它们在药物输送中的作用。

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.