Authors: Supriya D. Mahajan1, Indrajit Roy2, GaiXia Xu2, Ken-Tye Yong3, Hong Ding2, Ravikumar Aalinkeel1, Jessica L. Reynolds1, Donald E. Sykes1, Bindukumar B. Nair1, Elaine Y. Lin1, Paras N. Prasad2 and Stanley A. Schwartz1
Issue: Current HIV Research 2010 Jul; 8(5): 396–404.
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 and bioconjugation
- Department of Medicine, Division of Allergy, Immunology, and Rheumatology, State University of New York at Buffalo, 100 High street, Buffalo General Hospital, Buffalo, USA
- Institute for Lasers Photonics and Biophotonics, 428 Natural Science Complex, State University of New York at Buffalo, North campus, Buffalo, New York, NY 14260, USA
- School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore