Sustained-release Griffithsin nanoparticle-fiber composites against HIV-1 and HSV-2 infections.

Abstract

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.

• Authors: Kevin M Tyo, Amanda B Lasnik, Longyun Zhang, Mohamed Mahmoud, Alfred B Jenson, Joshua L Fuqua, Kenneth E Palmer, Jill M Steinbach-Rankins
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 321 Pg. 84-99 (05 10 2020) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 32035194 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Delayed-Action Preparations

Topics

• Animals
• Delayed-Action Preparations (therapeutic use)
• HIV Infections (drug therapy)
• HIV-1
• Herpesvirus 2, Human
• Mice
• Nanoparticles