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

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 benefi...

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Main Authors: Manish Kumar Jeengar, Mallesh Kurakula, Poonam Patil, Ashwini More, Ramakrishna Sistla, Deepti Parashar
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/4/1170
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author Manish Kumar Jeengar
Mallesh Kurakula
Poonam Patil
Ashwini More
Ramakrishna Sistla
Deepti Parashar
author_facet Manish Kumar Jeengar
Mallesh Kurakula
Poonam Patil
Ashwini More
Ramakrishna Sistla
Deepti Parashar
author_sort Manish Kumar Jeengar
collection DOAJ
description 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.
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spelling doaj.art-9315a5224e1f4ccea0037fbdba2c63112023-11-23T21:19:52ZengMDPI AGMolecules1420-30492022-02-01274117010.3390/molecules27041170Effect of Cationic Lipid Nanoparticle Loaded siRNA with Stearylamine against Chikungunya VirusManish Kumar Jeengar0Mallesh Kurakula1Poonam Patil2Ashwini More3Ramakrishna Sistla4Deepti Parashar5ICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, Maharashtra, IndiaCSIR-Indian Institute of Chemical Technology [CSIR-IICT], Hyderabad 500007, Telangana, IndiaICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, Maharashtra, IndiaICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, Maharashtra, IndiaCSIR-Indian Institute of Chemical Technology [CSIR-IICT], Hyderabad 500007, Telangana, IndiaICMR-National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune 411001, Maharashtra, IndiaChikungunya 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.https://www.mdpi.com/1420-3049/27/4/1170chikungunyanon-viral vectorscationic lipidssiRNAnanodelivery systemsstearylamine
spellingShingle Manish Kumar Jeengar
Mallesh Kurakula
Poonam Patil
Ashwini More
Ramakrishna Sistla
Deepti Parashar
Effect of Cationic Lipid Nanoparticle Loaded siRNA with Stearylamine against Chikungunya Virus
Molecules
chikungunya
non-viral vectors
cationic lipids
siRNA
nanodelivery systems
stearylamine
title Effect of Cationic Lipid Nanoparticle Loaded siRNA with Stearylamine against Chikungunya Virus
title_full Effect of Cationic Lipid Nanoparticle Loaded siRNA with Stearylamine against Chikungunya Virus
title_fullStr Effect of Cationic Lipid Nanoparticle Loaded siRNA with Stearylamine against Chikungunya Virus
title_full_unstemmed Effect of Cationic Lipid Nanoparticle Loaded siRNA with Stearylamine against Chikungunya Virus
title_short Effect of Cationic Lipid Nanoparticle Loaded siRNA with Stearylamine against Chikungunya Virus
title_sort effect of cationic lipid nanoparticle loaded sirna with stearylamine against chikungunya virus
topic chikungunya
non-viral vectors
cationic lipids
siRNA
nanodelivery systems
stearylamine
url https://www.mdpi.com/1420-3049/27/4/1170
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