Center for Personalized Nanomedicine, Institute of NeuroImmune Pharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA.
J Neurovirol. 2017 Aug;23(4):603-614. doi: 10.1007/s13365-017-0538-8. Epub 2017 Jul 31.
Drug abuse (e.g., methamphetamine-Meth or cocaine-Coc) is one of the major risk factors for becoming infected with HIV-1, and studies show that in combination, drug abuse and HIV-1 lead to significantly greater damage to CNS. To overcome these issues, we have developed a novel nanoformulation (NF) for drug-abusing population infected with HIV-1. In this work, a novel approach was developed for the co-encapsulation of Nelfinavir (Nel) and Rimcazole (Rico) using layer-by-layer (LbL) assembled magnetic nanoformulation for the cure of neuroAIDS. Developed NF was evaluated for blood-brain barrier (BBB) transmigration, cell uptake, cytotoxicity and efficacy (p24 assay) in HIV-1 infected primary astrocyte (HA) in presence or absence of Coc and Meth. Developed magnetic nanoformulation (NF) fabricated using the LbL approach exhibited higher amounts of drug loading (Nel and Rico) with 100% release of both the therapeutic agents in a sustained manner for 8 days. NF efficacy studies indicated a dose-dependent decrease in p24 levels in HIV-1-infected HA (55%) compared to Coc + Meth treated (50%). The results showed that Rico significantly subdued the effect of drugs of abuse on HIV infectivity. NF successfully transmigrated (38.8 ± 6.5%) across in vitro BBB model on the application of an external magnetic field and showed >90% of cell viability with efficient cell uptake. In conclusion, our proof of concept study revealed that sustained and concurrent release of sigma σ1 antagonist and anti-HIV drug from the developed novel sustained release NF can overcome the exacerbated effects of drugs of abuse in HIV infection and may solve the issue of medication adherence in the drug-abusing HIV-1 infected population.
药物滥用（例如冰毒-Meth 或可卡因-Coc）是感染 HIV-1 的主要危险因素之一，研究表明，药物滥用和 HIV-1 相结合会导致中枢神经系统（CNS）受到更大的损害。为了克服这些问题，我们为感染 HIV-1 的药物滥用人群开发了一种新型纳米制剂（NF）。在这项工作中，开发了一种新方法，用于使用层层（LbL）组装的磁性纳米制剂共包封奈非那韦（Nel）和里姆唑（Rico），以治疗神经艾滋病。在存在或不存在 Coc 和 Meth 的情况下，评估了开发的 NF 对血脑屏障（BBB）迁移、细胞摄取、细胞毒性和功效（p24 测定）的影响，用于感染 HIV-1 的原代星形胶质细胞（HA）。使用 LbL 方法制造的磁性纳米制剂（NF）表现出更高的药物负载量（Nel 和 Rico），两种治疗剂以持续的方式在 8 天内 100%释放。NF 功效研究表明，与 Coc+Meth 处理相比，感染 HIV-1 的 HA 中的 p24 水平呈剂量依赖性降低（~55%）。结果表明，Rico 显著抑制了滥用药物对 HIV 感染性的影响。NF 在应用外部磁场时成功地穿过体外 BBB 模型（38.8±6.5%），并具有 >90%的细胞活力和有效的细胞摄取。总之，我们的概念验证研究表明，从开发的新型缓释 NF 中持续和同时释放 sigma σ1 拮抗剂和抗 HIV 药物可以克服 HIV 感染中滥用药物的加剧作用，并可能解决药物滥用 HIV-1 感染人群中药物依从性的问题。
