**3. General conclusions and forthcoming work**

In general, the DNA-chitosan and DNA-pDADMAC systems revealed good colloidal properties and similar physicochemical features as compared one to each other. They were able to condense DNA plasmids to form particles small and positive enough so as to be taken up to cells by endocytosis; however, the transfection efficiency they rendered was markedly lower than that of the DNA-MEP lipoplex. With the experimental results here presented it appears that this low transfection efficiency relies on the high DNA-polycation binding affinity coupled with the structural conformation the polyplexes adopt in solution. Additionally, repulsive membrane acidolysis processes and different conformational transitions adopted by DOPE upon pH changes confer the MEP lipoplex a successful endosomal escape not occurring during polyplex transfection.

In light of the obtained results a deeper understanding of both the complex internalization to cells and DNA release from complexes to the cytoplasm must, in our opinion, be achieved in order to improve the transfection process. In the context of the DNA release, special attention needs be paid to the development of strategies assuring a high degree of DNA-vector de-compaction. Interesting pioneering results stem from publications by González-Pérez and coworkers (Carlstedt et al., 2010; Gonzalez-Perez & Dias, 2009; Gonzalez-Perez et al., 2008).
