调控细胞自噬实现控释抗逆转录病毒药物。
Modulating cellular autophagy for controlled antiretroviral drug release.
机构信息
Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Centre, Omaha, NE 68198, USA.
Department of Neurology, University of Rochester Medical Centre, Rochester, NY 14618, USA.
出版信息
Nanomedicine (Lond). 2018 Sep;13(17):2139-2154. doi: 10.2217/nnm-2018-0224. Epub 2018 Aug 21.
AIM
Pharmacologic agents that affect autophagy were tested for their abilities to enhance macrophage nanoformulated antiretroviral drug (ARV) depots and its slow release.
METHODS
These agents included URMC-099, rapamycin, metformin, desmethylclomipramine, 2-hydroxy-β-cyclodextrin (HBC) and clonidine. Each was administered with nanoformulated atazanavir (ATV) nanoparticles to human monocyte-derived macrophages. ARV retention, antiretroviral activity and nanocrystal autophagosomal formation were evaluated.
RESULTS
URMC-099, HBC and clonidine retained ATV. HBC, URMC-099 and rapamycin improved intracellular ATV retention. URMC-099 proved superior among the group in affecting antiretroviral activities.
CONCLUSION
Autophagy inducing agents, notably URMC-099, facilitate nanoformulated ARV depots and lead to sustained release and improved antiretroviral responses. As such, they may be considered for development as part of long acting antiretroviral treatment regimens.
目的
研究影响自噬的药物是否具有增强巨噬细胞纳米载药抗逆转录病毒药物（ARV）库及其缓慢释放的能力。
方法
这些药物包括 URMC-099、雷帕霉素、二甲双胍、去甲氯米帕明、2-羟-β-环糊精（HBC）和可乐定。将每种药物与纳米载药阿扎那韦（ATV）纳米颗粒一起用于人单核细胞衍生的巨噬细胞。评估 ARV 保留、抗逆转录病毒活性和纳米晶体自噬体形成。
结果
URMC-099、HBC 和可乐定保留 ATV。HBC、URMC-099 和雷帕霉素改善了细胞内 ATV 的保留。URMC-099 在影响抗逆转录病毒活性方面优于其他组。
结论
自噬诱导剂，特别是 URMC-099，可促进纳米载药 ARV 库的形成，并导致持续释放和改善抗逆转录病毒反应。因此，它们可能被考虑作为长效抗逆转录病毒治疗方案的一部分进行开发。
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