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

Annette E. LaBauve, Torri E. Rinker, Achraf Noureddine, Rita E. Serda, Jane Y. Howe, Michael Sherman, Amy Rasley, C. Jeffery Brinker, Darryl Y. Sasaki, Oscar A. Negrete

Research output: Contribution to journalArticle

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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 compared to PBS controls. Overall, these results highlight the utility of LC-MSNs as drug delivery vehicles to treat VEEV.

Original languageEnglish (US)
Article number13990
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Alphavirus Infections
Venezuelan Equine Encephalitis Viruses
Silicon Dioxide
Nanoparticles
Antiviral Agents
Lipids
Biological Warfare Agents
Pharmaceutical Preparations
Poisons
Virus Diseases
Endocytosis
Liposomes
Solubility

ASJC Scopus subject areas

  • General

Cite this

Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection. / LaBauve, Annette E.; Rinker, Torri E.; Noureddine, Achraf; Serda, Rita E.; Howe, Jane Y.; Sherman, Michael; Rasley, Amy; Brinker, C. Jeffery; Sasaki, Darryl Y.; Negrete, Oscar A.

In: Scientific Reports, Vol. 8, No. 1, 13990, 01.12.2018.

Research output: Contribution to journalArticle

LaBauve, AE, Rinker, TE, Noureddine, A, Serda, RE, Howe, JY, Sherman, M, Rasley, A, Brinker, CJ, Sasaki, DY & Negrete, OA 2018, 'Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection', Scientific Reports, vol. 8, no. 1, 13990. https://doi.org/10.1038/s41598-018-32033-w
LaBauve, Annette E. ; Rinker, Torri E. ; Noureddine, Achraf ; Serda, Rita E. ; Howe, Jane Y. ; Sherman, Michael ; Rasley, Amy ; Brinker, C. Jeffery ; Sasaki, Darryl Y. ; Negrete, Oscar A. / Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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