Results published so far show that azo-polymer-based colonic drug targeting is still in its infancy. It seems that microbial degradation of the investigated azo polymers is slow, and to date, no system is capable of delivering drugs completely and reproducibly within less than 6 h after entering the colon when the azo bond is located in the main chain,

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The effects of the redox mediator lawsone (2-hydroxy-1,4-naphthoquinone) on the ability of Escherichia coli to reduce anaerobically polymeric azo compounds were analysed. Two types of polymeric azo compounds were tested, that have been proposed as putative tools for the site-specific targeting of drugs to the colon. The first group of polymers consisted basically of linear chains of polymethacrylic acid or polymethylmethacrylate which were interrupted by subunits of 4,4'-bis(methacryloylamino)azobenzene. These polymers differed significantly in their hydrophilicity according to the relative proportion of polymethacrylic acid used for the polymerization procedure. The second group of polymers consisted of almost water-insoluble poly(ether-ester)azo polymers that were composed of 4-(6-hydroxyhexyl)oxy-phenylazobenzoate and 16-hydroxyhexadecanoate. The addition of lawsone to the anaerobically incubated cultures of E. coli resulted in a pronounced increase in the reduction rates of the water-soluble poly(methacrylate-co-4,4'-bis(methacryloylamino)azobenzene) and in a much smaller, but significant, increase in the reduction rates of the hydrophobic poly(ether-ester)azo polymers. An increase in the amount of azo groups resulted, for the hydrophobic poly(ether-ester)azo polymers, in an increased reduction rate in the presence of the redox mediator lawsone.

The purpose of this study was to investigate the influence of the composition of in-vitro azo-reducing systems on the degradation kinetics of the model compound amaranth. The degradation kinetics of amaranth were determined under anaerobic conditions both in rat caecal content (ex-vivo) and in a variety of in-vitro degradation media derived from rat caecal content. It was observed that the reducing activity was highly dependent on the preparation method and composition of the degradation medium. In pure rat caecal content, the degradation of amaranth was apparent first order (k = 0.044 +/- 0.002 min(-1)), while dilution of the rat caecal content resulted in an apparent zero-order degradation. Both apparent zero- and first-order degradations were also observed in media made up of diluted rat caecal content to which cofactors such as NADP, D-glucose-6-phosphate, glucose-6-phosphate dehydrogenase and Bz were added. This study demonstrates that in-vitro azo-reducing kinetics are dependent on the composition and mode of preparation of the in-vitro media used. This has to be taken into account when evaluating the degradability of azo-aromatic drug delivery systems in-vitro.