Cationic dextran

Dextran is a complex, branched glucan (a polysaccharide made of many glucose molecules) composed of chains of varying lengths (from 3 to 2,000 kilodaltons). It is used medicinally as an antithrombotic (antiplatelet) agent, to reduce blood viscosity, and as a volume expander in hypovolaemia. 

Dextran-spermine-based conjugates have been prepared via reductive amination between oxidised dextran and spermine [11]. Spermine, a naturally occurring linear polyamine, is involved in cellular metabolism and is a polycation at physiological pH. Dextran was initially oxidised with potassium periodate and the obtained dialdehyde derivative was then reacted under basic conditions with spermine. Dextran-spermine displayed particularly high transfection efficiency, which was attributed to the unique complexation properties between DNA and the grafted spermine moieties. Dextran-spermine and their derivatives have shown high transfection of p-DNA both in vitro and in vivo [12]. 

Cohen and co-workers combined the unique characteristics of acetyl-dextran (Ac-DEX) and spermine with small interfering RNA - a class of double-stranded RNA molecules, 20-25 base pairs in length - as a delivery system. Ac-DEX possesses several characteristics suitable for the delivery of bioactive agents such as proteins. The novel system combined ease of synthesis and biocompatibility with the advantage of controlled release, i.e., sensitivity to physiologically relevant acidic conditions. Acid-catalysed hydrolysis of spermine-Ac-DEX generated spermine-modified dextran, which could be further metabolised in vivo by enzymes [13]. 

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Dextran can be modified easily and cationic derivatives are obtained by reaction with diethylaminoethyl (DEAE) reagents or spermine. DEAE-dextran is one of the pioneer cationic polymers for gene delivery. However, PLL and other synthetic polymers have replaced dextran these days because of low transfection efficiency and toxicity problems of DEAE-dextran. Spermine-dextran (MW 9000-11 000 g mol ) is used as an siRNA delivery agent to cancer cells, with low toxicity and high loading capacity on HeLa-Zwc cells, and was proved to be a safe and effective acid-sensitive carrier for gene delivery by Cohen et al. Researchers showed that cationic dextran derivatives (MW 70 kDa) have also reverse tumor-associated macrophage (TAM) polarization, promote IL-12 expression in tumor TAMs and thereby enhance the tumoricidal capacity of TAMs. ... 

Studies show that PEI-grafted methacrylate nanocarriers are capable of transfection and DNA delivery. PEI (MW 25 kDa) also has immu-notherapeutic effects. Studies have showed that PEI reverses TAM polarization and evokes therapeutic anti-tumor immunity in a murine allograft tumor model like cationic dextran derivatives. ... 

Cationic dextran Polysaccharide with glucose units linked by a-1,6-linkages Drug delivery 21, 22... 

There are various modified forms of dextran available (Fig. 2.5). Nichifor et al. have widely reported about the fabrication of amphiphilic cationic dextrans, formerly crosslinked wifli epichlorohydrin or not, by replacing them with groups alike to the mentioned ones however in which one of the quaternary ammonium substituent s was an alkyl chain between C2 and C16 instead of methyl [24]. In this circumstance the reagent active for cationization was a 2,3-epoxypropyl alkyl dimethyl ammonium chloride derived from epichlorohydrin and a dimethyl alkylamine [24]. Products with a DS between 0.18 and 0.94 were derived The kinetic of the reaction of polysaccharides, with epichlorohydrin and various tertiary amines was investigated [24], by quantification of reagents and products in the reaction mixture with or without the presence the polysaccharide, at regular intervals. They reported fliat the use of cyclic amines e.g. 1-methyl-imidazol or 1,4-diazabicyclo [24] octan as catalysts together with another tertiary amine, used for the substitution, was not... 

Jo, J. 1., Nagaya, N., Miyahara, Y, Kataoka, M., Harada-Shiba, M., Kangawa, K., and Tabata, Y. 2007. Transplantation of genetically engineered mesenchymal stem cells improves cardiac function in rats with myocardial infarction Benefit of a novel nonviral vector, cationized dextran. Tissue Engineering, 13,313-322. 

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