Supramolecular hydrogels for enzymatically triggered self-immolative drug delivery

For the first time the combination of self-immolative spacers and supramolecular hydrogels has been tested in enzyme triggered drug release. Low-molecular weight drug-gelator conjugates have been prepared, which contain a gel forming lysine moiety linked to model drugs (benzylamine and phenethylamine) through a self-immolating spacer (p-aminobenzyloxycarbonyl). In the presence of trypsin the amide linkage between the gelator moiety and the spacer is hydrolyzed leading to the release of the model drug. This approach provides with distinct advantages, such as sustained release or versatility associated to the use of supramolecular hydrogels and self-immolative spacers, respectively.