Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires(UBA), Centro de Investigaciones en Hidratos de Carbono (CIHIDECAR), UBA-CONICET, Buenos Aires, Argentina.
Laboratorio de Estrategias Antivirales, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), UBA-CONICET, Buenos Aires, Argentina.
J Pharm Pharmacol. 2021 Mar 6;73(3):357-365. doi: 10.1093/jpp/rgaa045.
In the search of an effective antiviral formulation, the natural product curcumin (CUR) was encapsulated into poly(lactic-co-glycolic acid) nanoparticles, a non-toxic bioresorbable and biocompatible copolymer. The resulting CUR containing particles (PLGA-CUR NPs) were characterized and analysed for antiviral activity against Zika virus (ZIKV) infection.
The PLGA-CUR NPs were characterized by Fourier transform infrared, differential scanning calorimetry, dynamic light scattering, scanning electron microscopy and thermogravimetric analysis and release profile. Cytotoxicity of PLGA-CUR and the antiviral activity against ZIKV were determined in Vero cells. The effect of PLGA-CUR NPs on viral RNA synthesis and protein expression was analysed by RT-qPCR and immunofluorescence staining, respectively.
The PLGA-CUR NPs showed an appropriate in vitro drug release profile. Our studies of the antiviral activity of PLGA-CUR NPs and CUR against ZIKV by virus yield reduction as well as viral RNA synthesis and protein expression have shown that PLGA-CUR formulation is more effective than free CUR to inhibit ZIKV infection of Vero cells.
Our results demonstrate for the first time the antiviral activity against ZIKV of PLGA nanoparticles charged with CUR, suggesting that PLGA-CUR NPs are promising candidates for a drug formulation against human pathogenic flaviviruses.
在寻找有效的抗病毒制剂的过程中，将天然产物姜黄素（CUR）包封于聚乳酸-共-羟基乙酸（PLGA）纳米粒子中，这是一种无毒的可生物降解和生物相容的共聚物。对载有 CUR 的粒子（PLGA-CUR NPs）进行了表征，并分析了其对寨卡病毒（ZIKV）感染的抗病毒活性。
采用傅里叶变换红外光谱、差示扫描量热法、动态光散射、扫描电子显微镜和热重分析及释放曲线对 PLGA-CUR NPs 进行了表征。在 Vero 细胞中测定了 PLGA-CUR 的细胞毒性和抗 ZIKV 活性。通过 RT-qPCR 和免疫荧光染色分别分析了 PLGA-CUR NPs 对病毒 RNA 合成和蛋白表达的影响。
PLGA-CUR NPs 显示出适当的体外药物释放曲线。我们通过病毒产量减少以及病毒 RNA 合成和蛋白表达研究了 PLGA-CUR NPs 和 CUR 对 ZIKV 的抗病毒活性，结果表明，PLGA-CUR 制剂比游离 CUR 更能抑制 ZIKV 感染 Vero 细胞。
我们的研究结果首次证明了载有 CUR 的 PLGA 纳米粒子对 ZIKV 的抗病毒活性，这表明 PLGA-CUR NPs 是针对人类致病性黄病毒的药物制剂的有前途的候选物。
