title: Enhancing the delivery of anti retroviral drug "Saquinavir" across the blood brain barrier using nanoparticles.
abstract: Antiretroviral drugs are ineffective at treating viral infection in the brain because they cannot freely diffuse across the blood-brain barrier (BBB). Therefore, HIV-1 viral replication persists in the central nervous system (CNS) and continues to augment the neuropathogenesis process. Nanotechnology can play a pivotal role in HIV-1 therapeutics as it can increase drug solubility, enhance systemic bioavailability, and at the same time offer multifunctionality. Moreover, following conjugation with transferrin (Tf), these drug-loaded nanoformulations can permeate across biological barriers such as the blood brain barrier (BBB) via a receptor mediated transport mechanism. In the current study, we have stably incorporated the antiviral drug, Saquinavir, within Tf-conjugated quantum rods (QRs), which are novel nanoparticles with unique optical properties. We have evaluated the transversing ability of the QR-Tf-Saquinavir nanoformulation across an in vitro model of BBB. In addition, we have analyzed the subsequent antiviral efficacy of this targeted nanoformulation in HIV-1 infected peripheral blood mononuclear cells (PBMCs), which are cultured on the basolateral end of the in vitro BBB model. Our results show a significant uptake of QR-Tf-Saquinavir by brain microvascular endothelial cells (BMVECs), which constitute the BBB. In addition, we observed a significant enhancement in the transversing capability of QR-Tf-Saquinavir across the BBB, along with a marked decrease in HIV-1 viral replication in the PBMCs. These observations indicate that drug-loaded nanoparticles can deliver therapeutics across the BBB. These results highlight the potential of this nanoformulation in the treatment of Neuro-AIDS and other neurological disorders.
authors.affiliation: Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, Buffalo General Hospital, Buffalo, NY 14203, USA. smahajan@buffalo.edu
authors.forename: Supriya D
authors.initials: SD
authors.lastname: Mahajan
authors.forename: Indrajit
authors.initials: I
authors.lastname: Roy
authors.forename: Gaixia
authors.initials: G
authors.lastname: Xu
authors.forename: Ken-Tye
authors.initials: KT
authors.lastname: Yong
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Aalinkeel
authors.forename: Jessica
authors.initials: J
authors.lastname: Reynolds
authors.forename: Donald
authors.initials: D
authors.lastname: Sykes
authors.forename: Bindukumar B
authors.initials: BB
authors.lastname: Nair
authors.forename: Elaine Y
authors.initials: EY
authors.lastname: Lin
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 / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D042783:Endothelial Cells / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D043942:Nanotubes / Q000737:chemistry*; D019258:Saquinavir / Q000737:chemistry / Q000493:pharmacokinetics*; D014168:Transferrin / Q000737:chemistry / Q000493:pharmacokinetics*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers; D014168:Transferrin; D019258:Saquinavir