Synthesis of polyglutamine and dextran conjugates of streptomycin with an acid-sensitive drug-carrier linkage

A polymeric prodrug of streptomycin was prepared by coupling the drug via a spacer, glycine hydrazide, onto a polymeric carrier. In a first step, glycine N-Boc-hydrazide was linked to a 4-nitrophenyl chloroformate activated polymer. After removing the Boc group, streptomycin was coupled with the polymeric hydrazide with formation of a hydrazone bond. In order to target the drug-carrier derivative to the macrophages, 6-aminohexyl-alpha-D-mannopyranoside side groups were introduced. The polymeric streptomycin derivative was shown to be non hemolytic. The hydrolytic stability of the polymer-streptomycin conjugate was studied at physiological and lysosomal pH. Streptomycin release was found to be faster in the lysosomal pH range.