title: Nanoparticle-mediated targeted delivery of antiretrovirals to the brain.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Innovation Center, Buffalo, New York, USA.
authors.forename: Supriya D
authors.initials: SD
authors.lastname: Mahajan
authors.forename: Wing-Cheung
authors.initials: WC
authors.lastname: Law
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Aalinkeel
authors.forename: Jessica
authors.initials: J
authors.lastname: Reynolds
authors.forename: Bindukumar B
authors.initials: BB
authors.lastname: Nair
authors.forename: Ken-Tye
authors.initials: KT
authors.lastname: Yong
authors.forename: Indrajit
authors.initials: I
authors.lastname: Roy
authors.forename: Paras N
authors.initials: PN
authors.lastname: Prasad
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Schwartz
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D019187:Cadmium Compounds / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005663:Furans; D015870:Gene Expression; D016655:HIV Core Protein p24 / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D055806:Microvessels / Q000166:cytology / Q000378:metabolism; D058726:Nanoconjugates / Q000737:chemistry*; D010316:Particle Size; D061251:Primary Cell Culture; D045663:Quantum Dots; D018036:Selenium Compounds / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D014168:Transferrin / Q000737:chemistry; D019287:Zinc Sulfate / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D019187:Cadmium Compounds; D002219:Carbamates; D005663:Furans; D016655:HIV Core Protein p24; D058726:Nanoconjugates; D018036:Selenium Compounds; D013431:Sulfates; D013449:Sulfonamides; D014168:Transferrin; C514799:p24 protein, Human Immunodeficiency Virus Type 1; C095108:amprenavir; D019287:Zinc Sulfate; C037123:cadmium sulfate; C058667:cadmium selenide