Nanotechnology provides an opportunity to develop drug delivery systems that cross the blood brain barrier (BBB). However, as the production and discovery of new nanomaterials increases, identification of the toxic effects of nanomaterials is essential. Factors affecting toxicity include size of the nanoparticle (NP) as well as core material, drugs within the core, external functional groups, and surfactants. A standardized procedure to assess the toxicity of newly created nano-drug vehicles is highly desirable. This work will utilize an interdisciplinary approach to in vitro studies, providing a more comprehensive and accurate screening tool for toxicity. Specifically, the studies proposed will compare cellular toxicity measures, specific genes related to toxicity, and biophysical characteristics of NP interactions with model BBB membranes. This will enable the development of a standard panel of toxicity tests that can be conducted in a timely and relatively inexpensive fashion to investigate the toxicity of any type and number of NPs. In this work we will utilize the toxicity panel to characterize the effects of different charged surfactants on the toxicity of poly (butylcyanoacrylate) (PBCA) NPs, which have been shown to deliver drugs to the brain in animal models. While much research has been conducted on PBCA NPs, issues of toxicity have not been fully elucidated. Specific aims of this application include: (1) testing the toxicity of NPs using a two-cell culture model of the BBB;(2) examining a subset of genes related to (a) apoptosis and (b) stress and toxicity using PCR arrays;and (3) evaluating the biophysical characterization of NP-BBB model membrane interactions. This project fits well with the Academic Research Enhancement Award (AREA) R15 mechanism. Northern Kentucky University (NKU) is a primarily undergraduate institution but has not been a major recipient of NIH funding. The investigators and project faculty have strong active undergraduate research programs where students have the opportunity to present and publish their research. PUBLIC HEALTH RELEVANCE: More than one billion people across the world suffer with brain diseases, disorders, or injuries. To combat these maladies, researchers have been working hard to develop potential therapies, a majority of which may only be administered by injecting them directly into the brain. Nanotechnology has shown promise in delivering drugs to the brain that previously had not had access. The purpose of this application is to compare cellular toxicity measures, specific genes related to toxicity, and biophysical characteristics of model BBB membranes that have been exposed to a variety of nanoparticles. This will enable the development of a much needed standard panel of toxicity tests that can be conducted in a timely and relatively inexpensive fashion to investigate the toxicity of any type and number of nanoparticles.
NIH ExPorter
NIH ExPorter