Sustained-release Griffithsin nanoparticle-fiber composites against HIV-1 and HSV-2 infections.
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
10 05 2020
10 05 2020
Historique:
received:
21
10
2019
revised:
01
02
2020
accepted:
03
02
2020
pubmed:
9
2
2020
medline:
22
6
2021
entrez:
9
2
2020
Statut:
ppublish
Résumé
Human immunodeficiency virus (HIV-1) and herpes simplex virus 2 (HSV-2) affect hundreds of millions of people worldwide. The antiviral lectin, Griffithsin (GRFT), has been shown to be both safe and efficacious against HSV-2 and HIV-1 infections in vivo. The goal of this work was to develop a multilayered nanoparticle (NP)-electrospun fiber (EF) composite to provide sustained-release of GRFT, and to examine its safety and efficacy in a murine model of lethal HSV-2 infection. Composites were fabricated from polycaprolactone (PCL) fibers surrounding polyethylene oxide (PEO) fibers that incorporated methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) GRFT NPs. GRFT loading and release were determined via ELISA, showing that NP-EF composites achieved high GRFT loading, and provided sustained-release of GRFT for up to 90 d. The in vitro efficacy of GRFT NP-EFs was assessed using HIV-1 pseudovirus assays, demonstrating complete in vitro protection against HIV-1 infection. Additionally, sustained-release NP-EFs, administered 24 h prior to infection, prevented against a lethal dose of HSV-2 infection in a murine model. In parallel, histology and cytokine expression from murine reproductive tracts and vaginal lavages collected 24 and 72 h post-administration were similar to untreated mice, suggesting that NP-EF composites may be a promising and safe sustained-delivery platform to prevent HSV-2 infection. Future work will evaluate the ability to provide prolonged protection against multiple virus challenges, and different administration times with respect to infection.
Identifiants
pubmed: 32035194
pii: S0168-3659(20)30085-7
doi: 10.1016/j.jconrel.2020.02.006
pmc: PMC7170769
mid: NIHMS1560782
pii:
doi:
Substances chimiques
Delayed-Action Preparations
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
84-99Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM125504
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI113182
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
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