Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection

Scientific Reports
Annette E LaBauveOscar A Negrete

Abstract

Venezuelan equine encephalitis virus (VEEV) poses a major public health risk due to its amenability for use as a bioterrorism agent and its severe health consequences in humans. ML336 is a recently developed chemical inhibitor of VEEV, shown to effectively reduce VEEV infection in vitro and in vivo. However, its limited solubility and stability could hinder its clinical translation. To overcome these limitations, lipid-coated mesoporous silica nanoparticles (LC-MSNs) were employed. The large surface area of the MSN core promotes hydrophobic drug loading while the liposome coating retains the drug and enables enhanced circulation time and biocompatibility, providing an ideal ML336 delivery platform. LC-MSNs loaded 20 ± 3.4 μg ML336/mg LC-MSN and released 6.6 ± 1.3 μg/mg ML336 over 24 hours. ML336-loaded LC-MSNs significantly inhibited VEEV in vitro in a dose-dependent manner as compared to unloaded LC-MSNs controls. Moreover, cell-based studies suggested that additional release of ML336 occurs after endocytosis. In vivo safety studies were conducted in mice, and LC-MSNs were not toxic when dosed at 0.11 g LC-MSNs/kg/day for four days. ML336-loaded LC-MSNs showed significant reduction of brain viral titer in VEEV infected mice co...Continue Reading

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Citations

Mar 27, 2020·Current Topics in Medicinal Chemistry·Prasad MinakshiGaya Prasad
Sep 4, 2020·ChemPlusChem·Lili LiangGrzegorz Lisak
Feb 4, 2021·International Journal of Nanomedicine·Dongki Yang
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Oct 9, 2021·Scientific Reports·Cassandra M StawickiParag Mallick

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Methods Mentioned

BETA
transmission electron microscopy
scanning electron microscopy
PMA
flow cytometry
confocal microscopy
FCS
Fluorescence

Software Mentioned

GraphPad Prism
Leica Application Suite
FCS Express
ImageJ
DE

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