The goals of the Therapeutics core are to provide nanoformulations to invesfigators pursuing nanoformulated ntiretroviral and neuroprotective therapies for increased central nervous system (CNS) penetrance. The formulations developed address how monocytes and other immune cells may be harnessed for drug delivery. Before such novel therapies can be administered to people, we will determine, in well-validated laboratory and animal models, the optimal doses and formulation administration. The crux of the problem facing the Core, namely can nanoformulated antiretroviral therapy show sustained antiretroviral responses and slow release of drug in tissues, has now been addressed. The Core addresses a specific and important issue in the treatment of HIV and neuroAIDS, with broader implications for therapeutic interventions to other neurodegenerative diseases. Through this project, we will identify and manufacture candidate Nanoformulations of currently used efficacious antiretrovirals. These will be tested model systems of human disease, ranging from cultured monocytes to mice to monkeys, to examine pharmacokinefic, safety and efficacy. This Core, overall, represents work that may prove to be a major advance in the development of long-lasting therapeutic agents that can lead to real treatments both systemic and CNS human disease.

Public Health Relevance

The manufacture of nanosuspensions of poorly water-soluble antiretroviral drugs with high levels of drug loading will improve bioavailability to combat HIV/AIDS in hidden viral sanctuaries including the nervous system. Success will lay the foundation for a broad range of bench to bedside research towards pioneering long acting injectable drugs for CNS drug delivery.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Center Core Grants (P30)
Project #
5P30MH062261-14
Application #
8629789
Study Section
Special Emphasis Panel (ZMH1-ERB-M)
Project Start
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
14
Fiscal Year
2014
Total Cost
$176,883
Indirect Cost
$57,769
Name
University of Nebraska Medical Center
Department
Type
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Kelso, Matthew L; Elliott, Bret R; Haverland, Nicole A et al. (2015) Granulocyte-macrophage colony stimulating factor exerts protective and immunomodulatory effects in cortical trauma. J Neuroimmunol 278:162-73
Wilson, Tony W; Heinrichs-Graham, Elizabeth; Becker, Katherine M et al. (2015) Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV-infected older adults. Hum Brain Mapp 36:897-910
Gendelman, Howard E; Gelbard, Harris A (2014) Adjunctive and long-acting nanoformulated antiretroviral therapies for HIV-associated neurocognitive disorders. Curr Opin HIV AIDS 9:585-90
Johnson, Caroline H; Fisher, Timothy S; Hoang, Linh T et al. (2014) Luciferase does not Alter Metabolism in Cancer Cells. Metabolomics 10:354-360
Guo, Dongwei; Li, Tianyuzi; McMillan, JoEllyn et al. (2014) Small magnetite antiretroviral therapeutic nanoparticle probes for MRI of drug biodistribution. Nanomedicine (Lond) 9:1341-52
Sabouri, Amir H; Marcondes, Maria Cecilia Garibaldi; Flynn, Claudia et al. (2014) TLR signaling controls lethal encephalitis in WNV-infected brain. Brain Res 1574:84-95
Patti, Gary J; Tautenhahn, Ralf; Johannsen, Darcy et al. (2014) Meta-analysis of global metabolomic data identifies metabolites associated with life-span extension. Metabolomics 10:737-743
Haverland, Nicole A; Fox, Howard S; Ciborowski, Pawel (2014) Quantitative proteomics by SWATH-MS reveals altered expression of nucleic acid binding and regulatory proteins in HIV-1-infected macrophages. J Proteome Res 13:2109-19
Rinehart, Duane; Johnson, Caroline H; Nguyen, Thomas et al. (2014) Metabolomic data streaming for biology-dependent data acquisition. Nat Biotechnol 32:524-7
Villeneuve, Lance M; Stauch, Kelly L; Fox, Howard S (2014) Proteomic analysis of the mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands. J Proteomics 109:228-39

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