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首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Novel delivery system enhances efficacy of antiretroviral therapy in animal model for HIV-1 encephalitis.
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Novel delivery system enhances efficacy of antiretroviral therapy in animal model for HIV-1 encephalitis.

机译：新颖的递送系统增强了HIV-1脑炎动物模型中抗逆转录病毒疗法的功效。

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摘要

Most potent antiretroviral drugs (e.g., HIV-1 protease inhibitors) poorly penetrate the blood-brain barrier. Brain distribution can be limited by the efflux transporter, P-glycoprotein (P-gp). The ability of a novel drug delivery system (block co-polymer P85) that inhibits P-gp, to increase the efficacy of antiretroviral drugs in brain was examined using a severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). Severe combined immunodeficiency mice inoculated with HIV-1 infected human monocyte-derived macrophages (MDM) into the basal ganglia were treated with P85, antiretroviral therapy (ART) (zidovudine, lamivudine and nelfinavir (NEL)), or P85 and ART. Mice were killed on days 7 and 14, and brains were evaluated for levels of viral infection. Antiviral effects of NEL, P85, or their combination were evaluated in vitro using HIV-1 infected MDM and showed antiretroviral effects of P85 alone. In SCID mice injected with virus-infected MDM, the combination of ART-P85 and ART aloneshowed a significant decrease of HIV-1 p24 expressing MDM (25% and 33% of controls, respectively) at day 7 while P85 alone group was not different from control. At day 14, all treatment groups showed a significant decrease in percentage of HIV-1 infected MDM as compared with control. P85 alone and combined ART-P85 groups showed the most significant reduction in percentage of HIV-1 p24 expressing MDM (8% to 22% of control) that were superior to the ART alone group (38% of control). Our findings indicate major antiretroviral effects of P85 and enhanced in vivo efficacy of antiretroviral drugs when combined with P85 in a SCID mouse model of HIVE.
机译：大多数有效的抗逆转录病毒药物（例如HIV-1蛋白酶抑制剂）都无法很好地穿透血脑屏障。脑部分布可能受外排转运蛋白P-糖蛋白（P-gp）的限制。使用HIV-1脑炎（HIVE）的严重联合免疫缺陷（SCID）小鼠模型检查了抑制P-gp的新型药物递送系统（嵌段共聚物P85）增强脑中抗逆转录病毒药物功效的能力。用P85，抗逆转录病毒疗法（ART）（齐多夫定，拉米夫定和奈非那韦（NEL））或P85和ART对接种了HIV-1感染的人类单核细胞衍生巨噬细胞（MDM）的严重联合免疫缺陷小鼠进行治疗。在第7和14天杀死小鼠，并评估大脑的病毒感染水平。使用HIV-1感染的MDM在体外评估了NEL，P85或其组合的抗病毒作用，并显示了单独使用P85的抗逆转录病毒作用。在注射了病毒感染的MDM的SCID小鼠中，ART-P85和ART的组合在第7天显示出表达HIV-1 p24的MDM显着降低（分别为对照组的25％和33％），而单独的P85组没有差异从控制。在第14天，与对照组相比，所有治疗组均显示HIV-1感染的MDM百分比显着降低。单独的P85和联合的ART-P85组显示出HIV-1 p24表达MDM的百分比（对照组的8％至22％）下降幅度最大，优于单独的ART组（对照组的38％）。我们的发现表明，在HIVE的SCID小鼠模型中，与P85结合使用时，P85的主要抗逆转录病毒作用和增强的抗逆转录病毒药物的体内功效。

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