Journal
NATURE MATERIALS
Volume 8, Issue 6, Pages 526-533Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NMAT2444
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007950] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB000487] Funding Source: NIH RePORTER
- NHLBI NIH HHS [T32-HL007950-08, T32 HL007950] Funding Source: Medline
- NIBIB NIH HHS [R01 EB000487, R01-EB0000487-18, R01 EB000487-17, R01 EB000487-15, R01 EB000487-14, R01 EB000487-16] Funding Source: Medline
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Vaginal instillation of small-interfering RNA (siRNA) using liposomes has led to silencing of endogenous genes in the genital tract and protection against challenge from infectious disease. Although siRNA lipoplexes are easily formulated, several of the most effective transfection agents available commercially may be toxic to the mucosal epithelia and none are able to provide controlled or sustained release. Here, we demonstrate an alternative approach using nanoparticles composed entirely of FDA-approved materials. To render these materials effective for gene silencing, we developed novel approaches to load them with high amounts of siRNA. A single dose of siRNA-loaded nanoparticles to the mouse female reproductive tract caused efficient and sustained gene silencing. Knockdown of gene expression was observed proximal (in the vaginal lumen) and distal (in the uterine horns) to the site of topical delivery. In addition, nanoparticles penetrated deep into the epithelial tissue. This is the first report demonstrating that biodegradable polymer nanoparticles are effective delivery vehicles for siRNA to the vaginal mucosa.
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