DRUG DELIVERY TO THE BRAIN USING NOVEL NANOMATERIALS

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。 树枝状大分子是高度可定制的聚合物，作为基本的构建块，允许建立特定的纳米结构。该项目的目的是设计能够跨越血脑屏障(BBB)的树枝状大分子，以用于药物输送。本项目的目的是合成和表征新型的聚(赖氨酸)树状大分子和聚酰胺(PAMAM)树状大分子，每个树状大分子都有生物素标记或丹磺酰氯标记，以及表面基团，包括双胺(一种可能帮助树状大分子跨越血脑屏障的化合物)。此外，我们将使用衰减全反射红外光谱研究树枝状大分子对模型脂质双层的渗透；使用扫描探针显微镜表征固体/溶液界面上树枝状大分子纳米结构的基本相互作用；使用超高效液相色谱测量树枝状大分子通过脑内皮细胞和星形胶质细胞共同培养的细胞以及通过大鼠血脑屏障的通道。 (UPLC)和高效液相色谱仪。总的来说，这些研究将为树枝状大分子在药物输送和化学传感等应用中的使用提供有价值的信息。到目前为止，我们已经将所有G4和G5的PAMAM树枝状大分子共轭物晒黑，并向《纳米材料杂志》(与本科生共同作者)提交了一篇手稿。本文首次将UPLC分析作为一种监测PAMAM树枝状大分子表面转化(生物素)和产品质量的方法。目前，我们正在测试各种树状大分子在体外血脑屏障模型中的通过情况。教授导师罗伯特·约克尔将在接下来的两周内分享他在体内测试纳米颗粒通过老鼠血脑屏障的方法，皮马丁斯将前往英国完善这项技术。NIH R15拨款提案和SoMAS(神经科学导师及其学生支持)拨款提案目前正在审查中。授予了两份内部赠款提案。手稿也在准备中，用于表征和体外和体内研究。PiMartines前往德国马格德堡与马奇堡大学医学院建立合作关系，在那里将分享新的纳米颗粒(具有治疗胶质瘤的潜力)和新的体内模型，Trip得到NKU研究基金会的资助。

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. Dendrimers are highly customizable polymers that act as basic building blocks allowing specific nanostructures to be built. The purpose of this project is to design dendrimers that cross the blood brain barrier (BBB), for potential use in drug delivery. The aims of this project are to synthesize and charaterize novel poly(lysine) dendrimers and poly(amidoamine) (PAMAM) dendrimers, each with a biotin label or dansyl chloride label and surface groups including anandamide (a compound that may aid the dendrimer in crossing the BBB). Additionally, we will investigate dendrimer penetration into model lipid bilayers using attenuated total reflection infrared spectroscopy; characterize the fundamental interactions of dendrimer nanostructures at a solid/solution interface using scanning probe microscopy; measure the passage of dendrimers across a cell co-culture of brain endothelial cells and astrocytes and through the rat BBB, using ultra performance liquid chromatography (UPLC) and HPLC. Collectively, these studies will provide valuable information on the use of dendrimers in applications such as drug delivery and chemical sensing. This far, we have sunthesized all G4 and G5 PAMAM dendrimer conjugates and submitted a manuscript to Journal of Nanomaterials (with undergraduate student co-authors). In the paper, UPLC analysis was utilized for the first time as a methodology for monitoring PAMAM dendrimer surface transformations (biotin) and product quality. Currently, we are testing of passage of various dendrimers across the in vitro BBB model. Faculty Mentor Robert Yokel will share his in vivo method of testing nanoparticle passage across a rat BBB in the next 2 weeks as PI Martines will travel to UK to perfect this technique. An NIH R15 grant proposal and SOMAS (Support of Mentors and their Students in the Neurosciences) grant proposal are currently in review. Two internal grant proposals were awarded. Manuscripts are also in prepar ation for the characteriztion and in vitro and in vivo studies. PI Martines traveled to Magdeburg, Germany to establish a collaboration with the University of Madgeburg Medical School where new nanoparticles (with potential of treating glioma) and a new in vivo model will be shared, trip supported by NKU Research Foundation grant.