Polysaccharide−Oligoamine Based Conjugates for Gene Delivery

Abstract

This work describes a versatile and universal polycation system based on oligoamines grafted on natural polysaccharides that is capable of complexing various plasmids and administering them into various cells in high yield to produce a desired protein. These polycations are expected to better meet the requirements for effective complexation and delivery of plasmid or an antisense and to biodegrade into nontoxic components at a controlled rate. The developed biodegradable polycations are based on spermine, a natural tetramine, conjugated to dextran or arabinogalactan. These polycations were prepared by reductive amination of oxidized polysaccharides with the desired oligoamines. The Schiff base conjugates thus obtained were reduced to the stable amine conjugates by sodium borohydride. Over 300 different polycations were prepared starting from various polysaccharides and oligoamines, mainly oligoamines of two to four amino groups. Although most of these conjugates formed stable complexes with various plasmids as determined by turbidity experiments, only a few polycations were found to be active in transfecting cells. This work indicates that the structure of the polycation plays a significant role in the transfection activity of polycations.

Dextran–spermine polycation: an efficient nonviral vector for in vitro and in vivo gene transfection

“…The synthetic route of dextranspermine-based conjugates was found to be reproducible in terms of degree of conjugation and grafted spermine moieties (Table 1). 34 The in vitro transfection efficiencies of the synthetic conjugates, on the other hand, were also found to be reproducible in terms of gene level, but the weight-mixing ratio needed for optimal transfection varied from polymer to polymer. The optimal weightmixing ratio needed for transfection in all tested dextran-spermine conjugates was found to be in the range of 4-8 (polymer/DNA).…”

“…The particle size, charge, and the surface characteristics of the complex have a strong influence on the plasmid DNA body distribution and transfection efficiency. 24,26,[30][31][32][33] In recent publications, 34,35 we reported on a new class of biodegradable polycations capable of complexing and transfecting various genes to many cell lines in relatively high yields. More than 300 different polycations were prepared starting from various natural polysaccharides and oligoamines having two to four amino groups.…”

Novel dextran–spermine conjugates as transfecting agents: comparing water-soluble and micellar polymers

“…SPM conjugation to dextran by the reductive amination method [14][15][16] is a random reaction that may result in conjugates of various chemical compositions. Therefore, we studied the reproducibility of chemical composition and transfection efficiency.…”

“…Therefore, the nucleic acid can be released from the lysosome without degradation (endosomal escape). 11 In recent publications, [14][15][16] we reported on a new type of biodegradable water-soluble polycation based on spermine (SPM) grafted onto dextran (D-SPM, Figure 1a). In the current study, we evaluate the transfection efficiency of D-SPM-based polyplexes.…”

Biodegradable cationic polyester as an efficient carrier for gene delivery to neonatal cardiomyocytes

“…Numerous polymers including polyethyleneimine (PEI) (Boussif et al, 1995;Shuai et al, 2003), polylysine (PLL) (Kang et al, 2005), dendrimers (Bayele et al, 2005;Braun et al, 2005;Marano et al, 2005), poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) ( Van de Wetering et al, 1999), poly(ester amine)s (Zhong et al, 2005a,b), poly(D-glucaramidoamine) (Liu and Reineke, 2005;Liu and Reineke, 2006;Liu et al, 2004), and polysaccharideoligoamine based conjugates (Azzam et al, 2002;Yudovin-Farber et al, 2005) have been developed for gene delivery to other types of cells. For gene delivery to cardiomyocytes, polymer carriers must have low toxicity and be able to degrade into small molecules for exclusion from the cells.…”