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Development of new hybrid gene delivery carriers
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Gene therapy has gained increased attention over the last decades due to the possibility to treat a disease at its routes. Several vehicles intended to carry and deliver a functional copy of the deficient gene have been developed. Amongst these, viral vectors are highly effective systems, capable to deliver the genetic cargo to the nucleus. However, these carriers have raised safety concerns regarding to immunogenicity and insertional mutagenesis, creating the need to develop equally efficient vehicles with higher safety profiles. Therefore, non-viral vectors have been suggested as an alternative to viral gene transfer methods, as these overcome some of the drawbacks presented by viral vectors.
The main goal of this project was to develop safe and effective non-viral gene carriers, using solid lipid nanoparticles (SLNs) with surface modulated properties.
SLNs with surface modulated properties using polyethyleneimine (PEI) combined, or not, with protamine, were produced by hot high shear homogenization. The obtained particles possessed sizes <300 nm suitable for intravenous administration, and good physical stability for 3 months, under the different storage conditions tested (4ºC, room temperature and 37ºC). Moreover, these particles showed good plasmid condensation levels and were able to deliver the gene into the nucleus. Additionally, no cytotoxic effects concerning membrane integrity and metabolic activity of HEK 293-T cells were observed after 24 h of exposition.
In conclusion, the developed nanoparticles presented suitable properties for gene delivery, with high capacity to condense DNA and transfect cells without cytotoxicity.
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Gene delivery Non-viral vectors Cationic SLNs Hybrid nanoparticles Citotoxicity Transfection