Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of NeuroAIDS. Journal of immunology (Baltimore, Md. : 1950) [J Immunol] Journal article

Title	Macrophage delivery of nanoformulated antiretroviral drug to the brain in a murine model of NeuroAIDS.
Author(s)	Dou H, Grotepas CB, McMillan JM, Destache CJ, Chaubal M, Werling J, Kipp J, Rabinow B, Gendelman HE
Institution	Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, 68198, USA.
Source	J Immunol 2009 Jul 1; 183(1):661-9.
Abstract	Antiretroviral therapy (ART) shows variable blood-brain barrier penetration. This may affect the development of neurological complications of HIV infection. In attempts to attenuate viral growth for the nervous system, cell-based nanoformulations were developed with the focus on improving drug pharmacokinetics. We reasoned that ART carriage could be facilitated within blood-borne macrophages traveling across the blood-brain barrier. To test this idea, an HIV-1 encephalitis (HIVE) rodent model was used where HIV-1-infected human monocyte-derived macrophages were stereotactically injected into the subcortex of severe combined immunodeficient mice. ART was prepared using indinavir (IDV) nanoparticles (NP, nanoART) loaded into murine bone marrow macrophages (BMM, IDV-NP-BMM) after ex vivo cultivation. IDV-NP-BMM was administered i.v. to mice resulting in continuous IDV release for 14 days. Rhodamine-labeled IDV-NP was readily observed in areas of HIVE and specifically in brain subregions with active astrogliosis, microgliosis, and neuronal loss. IDV-NP-BMM treatment led to robust IDV levels and reduced HIV-1 replication in HIVE brain regions. We conclude that nanoART targeting to diseased brain through macrophage carriage is possible and can be considered in developmental therapeutics for HIV-associated neurological disease.
Language	eng
Pub Type(s)	Journal Article Research Support, N.I.H., Extramural
PubMed ID	19535632

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