Drug of abuse such as opiates have been shown to exert immunomodulatory effects and thereby serve as a cofactor in the progression of HIV-1 infection. Opiate and HIV target areas in brain such as basal ganglia and cortex that are enriched in 5 opioid receptors. Previous studies have shown that opiates act synergistically with HIV proteins (Tat and gp120) to potentiate HIV- related neurotoxicity, which ultimately leads to progression of NeuroAIDS. Currently, there is no treatment available to alleviate the synergistic effects of opiates and HIV, especially due to impenetrability of therapeutic molecules across the blood brain barrier (BBB). Therefore development of a drug delivery system containing an 5 opioid antagonist, a neuroprotective agent and ART that can cross BBB may have significant therapeutic advantage for treatment of opiate addiction and NeuroAIDS. In recent years, nanoparticle based delivery systems have shown promising approach for drug targeting to the brain. In the present proposal, we will develop a unique magnetically guided nanocarrier bound to CTOP (BBB impenetrable
This application has significant relevance to the purpose of the PAS-08-186, drug of abuse such as opiates have been shown to exert immunomodulatory effects and thereby serve as a cofactor in the progression of HIV-1 infection. Currently, there is no treatment available to alleviate the synergistic neurotoxicity of opiates and HIV, especially due to impenetrability of therapeutic molecules across the BBB. This project will evaluate a novel magnetically guided nanocarrier drug delivery system for simultaneous targeting of CTOP, BDNF and AZTTP across the BBB, thereby reduce opiate addiction and also NeuroAIDS in HIV infected subjects who are opiate users.
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