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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 药物传递技术是药物的重要组成部分，以达到预期的治疗效果。通常，这个问题与确定药物剂量、制剂和给药途径的药剂学研究有关。目前，许多小分子药物由于水溶性差或递送性质不足而没有充分利用其治疗潜力。抗癌剂如长春碱、阿霉素和紫杉醇可作为这类情况的良好例子。为了克服这些缺点，我们提出了一个纳米金刚石介导的局部递送模型化疗药物，盐酸阿霉素（Dox）的转换装置的化学机械性能建模。特别感兴趣的是预测未知的结构和表面性质的纳米金刚石功能化与羧基和碳酸分子的药物吸附。功能化纳米金刚石的配置将首先通过第一原理计算来预测。然后，进行分子水平的MC模拟，以预测的自组装过程和聚集体构型的ND和药物（即。Dox）。药物从纳米金刚石的解离以及随后通过paralyne的扩散将通过MD模拟来建模。可以从分子水平模拟中提取连续尺度扩散参数，以执行源自装置的药物扩散到目标区域的更宏观尺度的模拟。将研究许多材料参数，以了解它们对载药量和药物释放速率的影响。它们包括ND的尺寸分布，ND表面上的功能基团的密度，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ND的结构和表面性质及其在药物递送中的作用。

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.