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J Control Release. 2012 Aug 20;162(1):102-10. doi: 10.1016/j.jconrel.2012.06.008. Epub 2012 Jun 15.

Polymer nanoparticles encapsulating siRNA for treatment of HSV-2 genital infection.

Author information

1
Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.

Abstract

Effective, low-cost, and safe treatments for sexually transmitted viral infections are urgently needed. Here, we show for the first time that intravaginal administration with nanoparticles of poly(lactic-co-glycolic acid) (PLGA) encapsulating short interfering RNA (siRNA) molecules is effective for prevention of genital HSV-2 infections in mice. PLGA nanoparticles (NPs) were designed to interfere with HSV-2 infection by siRNA-mediated knockdown of nectin, a host cell protein. NPs were characterized in vitro to determine the optimal formulation based on siRNA loading, controlled release profile, and mRNA knockdown. Mice inoculated intravaginally with a lethal dose of HSV-2, and treated with PLGA NPs, showed increased survival from ~9 days (in untreated mice) to >28 days (in PLGA NP treated mice) - the longest survival ever observed with siRNA treatment in this mouse model. This work provides proof-of-concept that topical administration of NPs containing siRNA against a pathologically relevant host cell target can knockdown the gene in tissue and improve survival after HSV-2 infection. Furthermore, this system provides a safe delivery platform that employs materials that are already approved by the FDA and can be modified to enhance delivery of other microbicides.

PMID:
22705461
PMCID:
PMC3543782
DOI:
10.1016/j.jconrel.2012.06.008
[Indexed for MEDLINE]
Free PMC Article

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