Effect of Cationic Lipid Nanoparticle Loaded siRNA with Stearylamine against Chikungunya Virus

Abstract

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.

Design and In Vitro Evaluation of Novel Cationic Lipids for siRNA Delivery in Breast Cancer Cell Lines

“…In recent years, cationic lipid-based siRNA therapy had an excellent contribution to the treatment of several diseases [ 6 ]. There are several reports on the use of cationic lipid-based gene delivery for treating diseases [ 7 – 9 ]. There are different viral and nonviral delivery vectors available.…”

Targeted in vitro gene silencing of E2 and nsP1 genes of chikungunya virus by biocompatible zeolitic imidazolate framework

“…It might be due to the concentration of Lipofectamine 2000 used to transfect the siRNA might not be enough to serve as an effective carrier as a result of which, adequate levels of siRNA could not be delivered to the cells to initiate RNAi. Due to the restrictions of cytotoxicity (∼15–20%) in Vero CCL-81 cells, the concentration of Lipofectamine 2000 used could not be increased any further ( Jeengar et al, 2022 ).…”

“…siRNA targeted against E2 and nsP1 genes (designated as Chik1 and Chik5, respectively) were designed using HP OnGuard siRNA design and synthesized (Qiagen, Germany) as described previously ( Parashar et al, 2013 ). The minimum effective dose of siRNA as was investigated earlier to be 400 pM ( Jeengar et al, 2022 ), was used during the synthesis of siRNA encapsulated ZIF-C nanoparticles.…”

Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives

“…It distributes asymmetrically in the lipid bilayer, located mainly on the outer surface of the liposomes [41]. Studies on SA-nanoparticles showed increased stability, minimised drug leakage, and a controlled release profile [42]. However, cytotoxicity limits the clinical use of SA as the hydrophilic nitrogen 'head' group of the molecule interacts with certain enzymes [36,42].…”

“…Studies on SA-nanoparticles showed increased stability, minimised drug leakage, and a controlled release profile [42]. However, cytotoxicity limits the clinical use of SA as the hydrophilic nitrogen 'head' group of the molecule interacts with certain enzymes [36,42]. Other works reported apoptosis induced by SA generating reactive oxygen species, activating protein kinase C, or enhancing the release of apoptosis-dependent proteins, and hemolysis arising from the interaction between the molecule and the negatively charged erythrocyte membrane [43,44].…”