Enhancing the Delivery of Anti Retroviral Drug “Saquinavir” Across the Blood Brain Barrier Using Nanoparticles

Author(s): Supriya D. Mahajan, Indrajit Roy, GaiXia Xu, Ken-Tye Yong, Hong Ding, Ravikumar Aalinkeel, Jessica L. Reynolds, Donald E. Sykes, Bindukumar B. Nair, Elaine Y. Lin, Paras N. Prasad, Stanley A. Schwartz

Journal Name: Current HIV Research
HIV and Viral Immune Diseases

Volume 8 , Issue 5 , 2010


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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.

Keywords: HIV-1, antiretroviral drugs, saquinavir, protease inhibitor, quantum rods (QR), blood brain barrier, transferrin receptor, multimodal nanoparticles, bioconjugation

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Article Details

VOLUME: 8
ISSUE: 5
Year: 2010
Published on: 01 March, 2012
Page: [396 - 404]
Pages: 9
DOI: 10.2174/157016210791330356
Price: $65

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