New gene delivery system based on oligochitosan and solid lipid nanoparticles: ‘In vitro’ and ‘in vivo’ evaluation

Abstract

In the present work, we evaluated the potential utility for gene delivery of three oligochitosans (OligoCh) that differs in the Mn (OligoChA: 6.1kDa, OligoChB: 11.5kDa, and OligoChC: 13.7kDa), with deacetylation degree of 85%. OligoCh were complexed directly with the pCMS-EGFP plasmid to form OligoCh–DNA carriers. Taking into account the features and benefits of both Ch and SLNs, we also combined the OligoCh with SLNs. The three OligoCh presented a great ability to condense and protect the DNA. The OligoCh of highest Mn (OligoChC) complexed with SLNs at a OligoChC:DNA:SLN ratio 2.5:1:5 induced the highest transfection level in HEK-293 cells at day 3; being transfection 2-fold higher at day 7. After the intravenous administration to mice, OligoChC–DNA and OligoChC–DNA–SLN vectors were able to induce the expression of EGFP in the spleen, lung and liver, which was maintained for at least 7days. In spite of the difference in the “in vitro” transfection levels between both vectors, no difference was detected in transfection after “in vivo” administration. Moreover, the OligoChC improved the “in vivo” transfection efficacy of the DNA–SLN vector. This work shows the potential utility of the combination of SLNs and OligoCh for the development of new non-viral vectors for gene therapy.