ICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, Maharashtra, India.
Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682041, Kerala, India.
Molecules. 2022 Feb 9;27(4):1170. doi: 10.3390/molecules27041170.
Chikungunya is an infectious disease caused by mosquito-transmitted chikungunya virus (CHIKV). It was reported that NS1 and E2 siRNAs administration demonstrated CHIKV inhibition in in vitro as well as in vivo systems. Cationic lipids are promising for designing safe non-viral vectors and are beneficial in treating chikungunya. In this study, nanodelivery systems (hybrid polymeric/solid lipid nanoparticles) using cationic lipids (stearylamine, C9 lipid, and dioctadecylamine) and polymers (branched PEI-g-PEG -PEG) were prepared, characterized, and complexed with siRNA. The four developed delivery systems (F1, F2, F3, and F4) were assessed for stability and potential toxicities against CHIKV. In comparison to the other nanodelivery systems, F4 containing stearylamine (Octadecylamine; ODA), with an induced optimum cationic charge of 45.7 mV in the range of 152.1 nm, allowed maximum siRNA complexation, better stability, and higher transfection, with strong inhibition against the E2 and NS1 genes of CHIKV. The study concludes that cationic lipid-like ODA with ease of synthesis and characterization showed maximum complexation by structural condensation of siRNA owing to high transfection alone. Synergistic inhibition of CHIKV along with siRNA was demonstrated in both in vitro and in vivo models. Therefore, ODA-based cationic lipid nanoparticles can be explored as safe, potent, and efficient nonviral vectors overcoming siRNA in vivo complexities against chikungunya.
基孔肯雅热是一种由蚊媒传播的基孔肯雅病毒（CHIKV）引起的传染病。有报道称，NS1 和 E2 siRNA 的给药在体外和体内系统中均显示出对 CHIKV 的抑制作用。阳离子脂质体有望设计安全的非病毒载体，并有利于治疗基孔肯雅热。在这项研究中，使用阳离子脂质体（硬脂胺、C9 脂质和二硬脂酰基胺）和聚合物（支化的 PEI-g-PEG-PEG）制备、表征和复合了纳米递药系统（混合聚合物/固体脂质纳米粒）。评估了四种开发的递药系统（F1、F2、F3 和 F4）对 CHIKV 的稳定性和潜在毒性。与其他纳米递药系统相比，含硬脂胺（十八胺；ODA）的 F4 在 152.1nm 范围内具有 45.7mV 的最佳正电荷，允许最大程度地复合 siRNA，更好的稳定性和更高的转染效率，并对 CHIKV 的 E2 和 NS1 基因具有强烈的抑制作用。该研究得出结论，阳离子脂质样 ODA 具有易于合成和表征的特点，由于高转染效率，通过 siRNA 的结构缩合显示出最大的复合能力。在体外和体内模型中均证明了 CHIKV 与 siRNA 的协同抑制作用。因此，基于 ODA 的阳离子脂质体纳米粒可以作为安全、有效和高效的非病毒载体，克服针对基孔肯雅热的 siRNA 体内复杂性。
