Hyaluronic acid/chitosan-g-poly(ethylene glycol) nanoparticles for gene therapy: an application for pDNA and siRNA delivery.
OBJECTIVE
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.
Raviña
Manuela
M
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Avda. de las Ciencias s/n, Santiago de Compostela, Spain.
Cubillo
Eva
E
Olmeda
David
D
Novoa-Carballal
Ramón
R
Fernandez-Megia
Eduardo
E
Riguera
Ricardo
R
Sánchez
Alejandro
A
Cano
Amparo
A
Alonso
María José
MJ
D001483:Base Sequence; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage*; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D053758:Nanoparticles; D010957:Plasmids; D011092:Polyethylene Glycols / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D006820:Hyaluronic Acid; D004247:DNA; D048271:Chitosan