Enhancing the delivery of anti retroviral drug "Saquinavir" across the blood brain barrier using nanoparticles.
Enhancing the delivery of anti retroviral drug "Saquinavir" across the blood brain barrier using nanoparticles.
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DOI：
10.2174/157016210791330356
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发表时间：
2010-07
影响因子：
1
通讯作者：
Schwartz SA
中科院分区：
文献类型：
--
作者：
Mahajan SD;Roy I;Xu G;Yong KT;Ding H;Aalinkeel R;Reynolds J;Sykes D;Nair BB;Lin EY;Prasad PN;Schwartz SA
抗逆转录病毒药物在治疗大脑中的病毒感染方面是无效的，因为它们不能自由地扩散穿过血脑屏障（BBB）。因此，HIV-1病毒复制持续存在于中枢神经系统（CNS），并继续增加神经发病过程。纳米技术可以在HIV-1治疗中发挥关键作用，因为它可以增加药物溶解度，提高全身生物利用度，同时提供多功能性。此外，在与转铁蛋白（Tf）缀合后，这些载药纳米制剂可以通过受体介导的转运机制渗透穿过生物屏障，例如血脑屏障（BBB）。在目前的研究中，我们已经将抗病毒药物沙奎那韦稳定地结合在Tf共轭量子棒（QR）中，这是一种具有独特光学性质的新型纳米颗粒。我们已经评估了QR-Tf-沙奎那韦纳米制剂在体外BBB模型中的横向能力。此外，我们还分析了这种靶向纳米制剂在HIV-1感染的外周血单核细胞（PBMC）中的后续抗病毒功效，这些细胞在体外BBB模型的基底外侧端培养。我们的研究结果表明，QR-Tf-沙奎那韦脑微血管内皮细胞（BMVECs），构成了血脑屏障的显着摄取。此外，我们观察到QR-Tf-沙奎那韦穿过BBB的能力显著增强，沿着PBMC中HIV-1病毒复制的显著降低。这些观察结果表明，载药纳米颗粒可以通过BBB递送治疗剂。这些结果突出了这种纳米制剂在治疗神经艾滋病和其他神经系统疾病中的潜力。
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.
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影响因子：
3.7
作者：
Gulyaev, AE;Gelperina, SE;Kreuter, J
通讯作者：
Kreuter, J
影响因子：
3.5
作者：
Bustin, SA
通讯作者：
Bustin, SA
影响因子：
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作者：
Silva, Gabriel A.
通讯作者：
Silva, Gabriel A.
影响因子：
5.3
作者：
Pathak, S;Cao, E;Silva, GA
通讯作者：
Silva, GA
影响因子：
4.7
作者：
Xu, Gaixia;Yong, Ken-Tye;Prasad, Paras N.
通讯作者：
Prasad, Paras N.