Polymeric drag conjugates

Khandare J, Minko T (2006) Polymer-drag conjugates progress in polymeric prodrags. Prog Polym Sd 31 359-397... 

A famous example of multifunctionality in polymeric materials for biomedical applications is the concept of polymer-drag conjugates as introduced by Ringsdorf in 1975 [3] (Fig. 5.2). The various functionalities are introduced by a combination of copolymerization and polymer analogous reactions. It has to be noted that for drug delivery carrier polymers, not only the functionality but also the molar mass are of high importance for the apphcation since it defines not only the solubihty but also the half-life time in blood and the uptake in specific cells and the excretion from the kidneys. 

The preferred mode for dmg administration is undoubtedly the oral route, but the efficiency of oral administration is often limited by premature uptake or degradation. For dmgs that need to enter systemic circulation, the adsorption window is situated in the upper intestine. For treatment of inflammations in the lower part of the GI tract, uptake in the small intestine is to be avoided. A typical example is the treatment of ulcerative colitis and Crohn s disease with 5-aminosa-licylic acid (5-AS A). The parent drag is not efficient because of premature uptake in the upper intestine. One possible solution is the use of polymeric conjugates of 5-ASA linked to a polymeric carrier via an azo bond. It is well known that the colon is a reductive medium that can split azo bonds with formation of amino constituents. It is anticipated that polymer-5-ASA conjugate will pass intact through the upper part of the GI tract and reach the colon, where 5-ASA will be released. We have prepared in our laboratory a series of azo-coupled polymer-5-ASA conjugates (Fig. 34.10). 

Yokoyama, M., Miyauchi, M., Yamada, N., Okano, T., Sakurai, Y., Kataoka, K. and Inoue, S. (1990) Characterization and anticancer activity of the micelle forming polymeric anti-cancer drag adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer. Cancer Res. 50 1693-1700. 

Fig. 4 (a) Structural formula of doxOTubicin-conjugated PEG-i>-poly(aspartate) copolymers, (b) The concept of micelle-forming polymeiie drags, as reported in [29]. The optimized formulation of these micelles was the first elinieally tested polymeric micelles (NK911)... 

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