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.
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.
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|Hu, Guoku; Liao, Ke; Niu, Fang et al. (2018) Astrocyte EV-Induced lincRNA-Cox2 Regulates Microglial Phagocytosis: Implications for Morphine-Mediated Neurodegeneration. Mol Ther Nucleic Acids 13:450-463|
|Schutt, Charles R; Gendelman, Howard E; Mosley, R Lee (2018) Tolerogenic bone marrow-derived dendritic cells induce neuroprotective regulatory T cells in a model of Parkinson's disease. Mol Neurodegener 13:26|
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