Polymer nanoparticles encapsulating siRNA for treatment of HSV-2 genital infection.
J Control Release
; 162(1): 102-10, 2012 Aug 20.
Article
in En
| MEDLINE
| ID: mdl-22705461
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Herpes Genitalis
/
Cell Adhesion Molecules
/
Herpesvirus 2, Human
/
RNA, Small Interfering
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Nanoparticles
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Host-Pathogen Interactions
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
J Control Release
Journal subject:
FARMACOLOGIA
Year:
2012
Document type:
Article
Affiliation country:
United States