skip to main content

DOE PAGESDOE PAGES

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

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. Here, 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 deliverymore » vehicles to treat VEEV.« less
Authors:
 [1] ;  [1] ;  [2] ;  [2] ;  [3] ;  [4] ;  [5] ;  [2] ;  [1] ;  [1]
  1. Sandia National Lab. (SNL-CA), Livermore, CA (United States). Dept. of Biotechnology and Bioengineering
  2. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Advanced Materials Lab.; Univ. of New Mexico, Albuquerque, NM (United States). Chemical and Biological Engineering; Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials, Advanced Materials Lab.
  3. Hitachi High Technologies America Inc., Clarksburg, MD (United States)
  4. Univ. of Texas Medical Branch, Galveston, TX (United States). Sealy Center for Structural Biology & Molecular Biophysics
  5. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Biosciences and Biotechnology Division
Publication Date:
Report Number(s):
SAND-2018-10167J
Journal ID: ISSN 2045-2322; 667926
Grant/Contract Number:
AC04-94AL85000; 190245; NA0003525; 1002720595
Type:
Published Article
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Research Org:
Sandia National Lab. (SNL-CA), Livermore, CA (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Sponsoring Org:
USDOE National Nuclear Security Administration (NNSA); USDOE Laboratory Directed Research and Development (LDRD) Program
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES
OSTI Identifier:
1469731
Alternate Identifier(s):
OSTI ID: 1474053

LaBauve, Annette E., Rinker, Torri E., Noureddine, Achraf, Serda, Rita E., Howe, Jane Y., Sherman, Michael B., Rasley, Amy, Brinker, C. Jeffery, Sasaki, Darryl Y., and Negrete, Oscar A.. Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection. United States: N. p., Web. doi:10.1038/s41598-018-32033-w.
LaBauve, Annette E., Rinker, Torri E., Noureddine, Achraf, Serda, Rita E., Howe, Jane Y., Sherman, Michael B., 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. United States. doi:10.1038/s41598-018-32033-w.
LaBauve, Annette E., Rinker, Torri E., Noureddine, Achraf, Serda, Rita E., Howe, Jane Y., Sherman, Michael B., Rasley, Amy, Brinker, C. Jeffery, Sasaki, Darryl Y., and Negrete, Oscar A.. 2018. "Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection". United States. doi:10.1038/s41598-018-32033-w.
@article{osti_1469731,
title = {Lipid-Coated Mesoporous Silica Nanoparticles for the Delivery of the ML336 Antiviral to Inhibit Encephalitic Alphavirus Infection},
author = {LaBauve, Annette E. and Rinker, Torri E. and Noureddine, Achraf and Serda, Rita E. and Howe, Jane Y. and Sherman, Michael B. and Rasley, Amy and Brinker, C. Jeffery and Sasaki, Darryl Y. and Negrete, Oscar A.},
abstractNote = {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. Here, 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.},
doi = {10.1038/s41598-018-32033-w},
journal = {Scientific Reports},
number = 1,
volume = 8,
place = {United States},
year = {2018},
month = {9}
}

Works referenced in this record:

Porous Nanoparticle Supported Lipid Bilayers (Protocells) as Delivery Vehicles
journal, February 2009
  • Liu, Juewen; Stace-Naughton, Alison; Jiang, Xingmao
  • Journal of the American Chemical Society, Vol. 131, Issue 4, p. 1354-1355
  • DOI: 10.1021/ja808018y

Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers
journal, August 2008
  • Slowing, I.; Vivero-Escoto, J.; Wu, C.
  • Advanced Drug Delivery Reviews, Vol. 60, Issue 11, p. 1278-1288
  • DOI: 10.1016/j.addr.2008.03.012

Mesoporous silica nanoparticles in biomedical applications
journal, January 2012
  • Li, Zongxi; Barnes, Jonathan C.; Bosoy, Aleksandr
  • Chemical Society Reviews, Vol. 41, Issue 7, p. 2590-2605
  • DOI: 10.1039/c1cs15246g