DRUG DELIVERY TO THE BRAIN USING NOVEL NANOMATERIALS

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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.