Biomaterials, Biodegradables and Biomimetics Research Group

Papers in Scientific Journals

Hyaluronic Acid/Chitosan-g-Poly(ethylene glycol) Nanoparticles for Gene Therapy: An Application for pDNA and siRNA Delivery

Abstract

Purpose

To design hyaluronic acid (HA) and chitosan-g-poly(ethylene glycol) (CS-g-PEG) nanoparticles intended for a broad range of gene delivery applications.

Methods

Nanoparticles formulated at different HA/CS-g-PEG mass ratios were developed to associate either pDNA or siRNA. The physico-chemical characteristics, morphology, association efficiency and nuclease protection ability of the nanocarriers were compared for these two molecules. Their biological performance, including transfection effciency, nanoparticle cellular uptake and citotoxicity, was assesed.

Results

The resulting nanoparticles showed an adequate size (between 130 and 180 nm), and their surface charge could be modulated according to the nanoparticle composition (from +30 mV to −20 mV). All prototypes exhibited a greater association efficiency and nuclease protection for pDNA than for siRNA. However, cell culture experiments evidenced that HA/CS-g-PEG nanoparticles were effective carriers for the delivery of both, siRNA and pDNA, eliciting a biological response with minimal cytotoxicity. Moreover, experiments performed in the HEK-EGFP-Snail1 cell line showed the potential of the HA/CS-g-PEG nanoparticles to silence the expression of the Snail1 transcription factor, an important mediator in tumor progression.

Conclusions

HA/CS-g-PEG nanoparticles can be easily modulated for the delivery of different types of gene molecules, offering great potential for gene therapy applications, as evidenced by their biological performance.

Journal
Pharmaceutical Research
Volume
27
Pagination
2544
Keywords
Chitosan, Gene delivery, Hyaluronan; PEG
Rights
Restricted Access
Peer Reviewed
Yes
Status
published
Year of Publication
2010
Date Published
2010-12-01
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