Methods in Enzymology 2012-01-01

Nanoparticle-mediated targeted delivery of antiretrovirals to the brain.

Supriya D Mahajan, Wing-Cheung Law, Ravikumar Aalinkeel, Jessica Reynolds, Bindukumar B Nair, Ken-Tye Yong, Indrajit Roy, Paras N Prasad, Stanley A Schwartz

文献索引：Meth. Enzymol. 509 , 41-60, (2012)

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摘要

Nanotechnology offers a new platform for therapeutic delivery of antiretrovirals to the central nervous system (CNS) where human immunodeficiency virus (HIV-1) is sequestered in patients with HIV-1-associated neurological disorders (HAND). HAND is a spectrum of neurocognitive disorders that continue to persist in HIV-1-infected patients in spite of successful highly active antiretroviral therapy (HAART). Nanoformulated antiretroviral drugs offer multifunctionality, that is, the ability to package multiple diagnostic and therapeutic agents within the same nanocomposite, along with the added provisions of site-directed delivery, delivery across the blood-brain barrier (BBB), and controlled release of therapeutics. We have stably incorporated the antiretroviral drug, Amprenavir, within a transferrin (Tf)-conjugated quantum dot (QD), and evaluated the transversing ability of this Tf-QD-Amprenavir nanoplex across an in vitro BBB model and analyzed its antiviral efficacy in HIV-1-infected monocytes. We describe methods for synthesis of the Tf-QD-Amprenavir nanoplex and approaches to evaluate both its BBB transversing capability and antiviral efficacy.Copyright © 2012 Elsevier Inc. All rights reserved.