Polymeric activated dextrans

Bis-hydrazide-containing molecules also can be used to activate soluble polymeric sub-stances-containing aldehyde groups. For instance, dextran may be periodate oxidized to create numerous formyl functionalities on each molecule. Subsequent reaction with a homobifunctional hydrazide in large excess results in a hydrazide-activated polymer having multivalent-binding capability toward aldehydes or ketones (Chapter 25, Section 2.2). Insoluble support matrices suitable for affinity chromatography have been activated in a similar fashion to create the hydrazide derivative (O Shannessy and Wilchek, 1990). 

On the other hand, polymeric carriers can also be modified to introduce reactive groups. Polysaccharides such as dextran and inulin may be activated [149] by periodate oxidation to create aldehyde groups, by succinic anhydride activation to create carboxylic groups, or by p-nitrophenyl chloroformate activation to create reactive ester groups. 

Polymeric prodrugs are currently one of the most investigated topics. This research has resulted in breakthrough therapeutics, and many compounds are under clinical development (Table 3.7). Other examples of polymeric prodrug applications include the use of polysaccharides such as dextran, mannan, and pullulan to enable active targeting to tumor cells.117... 

Dextran - an oi(l->6) polymer of glucose with ot(l->2), ot(l->3), and ot(l->4) branch points. Dextran is the only polysaccharide listed here that does not use activated nucleotide sugars (or derivatives) in making the polymer. The polymerization, catalyzed by the enzyme dextran sucrase, is a transglycosylation of sucrose ... 

Takakura, Y., Kitajima, M., Matsumoto, S., Hashida, M. and Sezaki, H. (1987) Development of a novel polymeric prodrag of mitomycin C, mitomycin C-dextran conjugate with anionic charge. 1. Physicochemical characteristics and in vitro and in vivo antitumour activities. Int. J. Pharm. 37 135-143. 

Succinic esters of dextran have been prepared and transformed into the corresponding imidazolides, which react smoothly with alcohols or amines to yield the corresponding polymeric esters or amides. These activated amides may be of value for the preparation of polymer-drug adducts with a main backbone degradable to safe metabolites in the body fluids. 

Bernard et al. [105] used the same strategy to decorate polyVAc latex particles with a dithiocarbonate end-functionalized dextran (dextran-RAFT), well-suited for the CRP of non-activated vinyl esters such as VAc. Dextran-RAFT was obtained by Cu(I)-catalyzed Huisgen [3+2] dipolar cycloaddition [106] between an alkyne end-functionalized dextran and an azido-containing dithiocarbonate. The low functionalization yield (30%) was apparently not an impediment for the syntheses of stable poly VAc latex particles (diameters from 80 to 150 nm) via batch emulsion polymerization. The involvement of the dithiocarbonate end-group was corroborated by the retardation effect observed when the dextran-RAFT concentration was increased. In addition, a drastic effect on particle size was observed as compared to emulsion polymerization experiments performed with native or alkyne-functionalized dextran (particle diameter above 500 nm). 

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