Abstract
A series of succinoylated poly[N-(2-)- L-glutamine] (PHEG) derivatives was synthesized by reacting PHEG with succinic anhydride in the presence of N,N-dimethylaminopyridine as a catalyst. The size of the derivatives were measured by dynamic light scattering in buffers (pH 5.5 and 7.4, respectively) the lysosomal and physiological pH. The degradability of the succinoylated polymers toward cathepsin B was followed by gel permeation chromatography. It was demonstrated that an increase of modification results in decreased biodegradability. Conjugation of mitomycin C (MMC) with a succinoylated PHEG derivative through a collagenase-sensitive Pro-Leu-Gly-Pro- Leu spacer resulted in a water-soluble MMC conjugate. This conjugate was shown to be hydrolytically stable in buffers of lysosomal and physiological pH and able to release MMC in the presence of the bacterial collagenase clostridium histolyticum.
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