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

作者：Supriya D. Mahajan, Indrajit Roy, Gaixia Xu, Ken‐Tye Yong, Hong Yan Ding, Ravikumar Aalinkeel, Jessica L. Reynolds, Donald E. Sykes, Bindukumar B. Nair, Elaine Y. Lin, Paras N. Prasad, Stanley A. Schwartz · 发表于：Current HIV Research · 年份：2010 · DOI：10.2174/157016210791330356 · 被引用次数：96 · 研究领域：HIV Research and Treatment、Quantum Dots Synthesis And Properties、Advanced biosensing and bioanalysis techniques

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 vi...