Inhalable Curcumin: Offering the Potential for Translation to Imaging and Treatment of Alzheimer's Disease

Article type: Research Article

Authors: McClure, Richard^{a; b; c} | Yanagisawa, Daijiro^{d; e} | Stec, Donald^f | Abdollahian, Dave^{a; b} | Koktysh, Dmitry^{f; g} | Xhillari, Dritan^h | Jaeger, Rudolph^h | Stanwood, Gregg^{i; j} | Chekmenev, Eduard^{a; b; i; k} | Tooyama, Ikuo^{d; e} | Gore, John C.^{a; b; c; i; k; l} | Pham, Wellington^{a; b; c; i; k; m; *}

Affiliations: [a] Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA | [b] Department of Radiology and Radiological Sciences, Vanderbilt School of Medicine, Nashville, TN, USA | [c] Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA | [d] Shiga University of Medical Science, Otsu, Japan | [e] Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan | [f] Department of Chemistry, Vanderbilt University, Nashville, TN, USA | [g] Vanderbilt Institute of Nanoscale Science and Engineering, Nashville, TN, USA | [h] CH Technologies (USA) Inc., Westwood, NJ, USA | [i] Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA | [j] Department of Pharmacology, Vanderbilt University, Nashville, TN, USA | [k] Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA | [l] Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA | [m] Vanderbilt Institute of Chemical Biology, Nashville, TN, USA

Correspondence: [*] Correspondence to: Wellington Pham, PhD, Institute of Imaging Science, Vanderbilt University School of Medicine, 1161, 21st Avenue South, Nashville, TN +1 37232 2310, USA. Tel.: +1 615 936 7621; E-mail: [email protected].

Abstract: Curcumin is a promising compound that can be used as a theranostic agent to aid research in Alzheimer's disease. Beyond its ability to bind to amyloid plaques, the compound can also cross the blood-brain barrier. Presently, curcumin can be applied only to animal models, as the formulation needed for iv injection renders it unfit for human use. Here, we describe a novel technique to aerosolize a curcumin derivative, FMeC1, and facilitate its safe delivery to the brain. Aside from the translational applicability of this approach, a study in the 5XFAD mouse model suggested that inhalation exposure to an aerosolized FMeC1 modestly improved the distribution of the compound in the brain. Additionally, immunohistochemistry data confirms that following aerosol delivery, FMeC1 binds amyloid plaques expressed in the hippocampal areas and cortex.

Keywords: Aerosol, Alzheimer's disease, amyloid imaging, amyloid plaques, atomization, inhalation exposure, clinical translation, curcumin

DOI: 10.3233/JAD-140798

Journal: Journal of Alzheimer's Disease, vol. 44, no. 1, pp. 283-295, 2015