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.
|Villeneuve, Lance M; Purnell, Phillip R; Stauch, Kelly L et al. (2016) HIV-1 transgenic rats display mitochondrial abnormalities consistent with abnormal energy generation and distribution. J Neurovirol :|
|Li, Weizhe; Tong, Hsin-I; Gorantla, Santhi et al. (2016) Neuropharmacologic Approaches to Restore the Brain's Microenvironment. J Neuroimmune Pharmacol 11:484-94|
|Singh, Dhirender; McMillan, JoEllyn; Hilaire, James et al. (2016) Development and characterization of a long-acting nanoformulated abacavir prodrug. Nanomedicine (Lond) 11:1913-27|
|Sajja, Balasrinivasa R; Bade, Aditya N; Zhou, Biyun et al. (2016) Generation and Disease Model Relevance of a Manganese Enhanced Magnetic Resonance Imaging-Based NOD/scid-IL-2RÎ³c(null) Mouse Brain Atlas. J Neuroimmune Pharmacol 11:133-41|
|Jaeger, Philipp A; Lucin, Kurt M; Britschgi, Markus et al. (2016) Network-driven plasma proteomics expose molecular changes in the Alzheimer's brain. Mol Neurodegener 11:31|
|Bade, Aditya N; Gorantla, Santhi; Dash, Prasanta K et al. (2016) Manganese-Enhanced Magnetic Resonance Imaging Reflects Brain Pathology During Progressive HIV-1 Infection of Humanized Mice. Mol Neurobiol 53:3286-97|
|Zhang, Gang; Guo, Dongwei; Dash, Prasanta K et al. (2016) The mixed lineage kinase-3 inhibitor URMC-099 improves therapeutic outcomes for long-acting antiretroviral therapy. Nanomedicine 12:109-22|
|Burns, Ariel; Ciborowski, Pawel (2016) Acute exposure to methamphetamine alters TLR9-mediated cytokine expression in human macrophage. Immunobiology 221:199-207|
|Yang, Lu; Yao, Honghong; Chen, Xufeng et al. (2016) Role of Sigma Receptor in Cocaine-Mediated Induction of Glial Fibrillary Acidic Protein: Implications for HAND. Mol Neurobiol 53:1329-42|
|Dong, Weiguo; Embury, Christine M; Lu, Yaman et al. (2016) The mixed-lineage kinase 3 inhibitor URMC-099 facilitates microglial amyloid-Î² degradation. J Neuroinflammation 13:184|
Showing the most recent 10 out of 337 publications