Release of macromolecules and daunomycin from hydrophilic gels containing enzymatically degradable bonds.

The synthesis of hydrophilic gels based on N-(2-hydroxypropyl)methacrylamide copolymers crosslinked via degradable oligopeptide sequences is described. The influence of the conditions of preparation and of the gel structure on the equilibrium degree of swelling (network density) was determined. To evaluate the potential of such gels for controlled delivery of macromolecules and drugs, the release of FITC-dextrans of different molecular weights was studied and the rate of release was found to depend mainly on the equilibrium degree of swelling and not on the structure of the crosslinks. However, the degradation of the gels by a mixture of lysosomal enzymes isolated from rat liver (Tritosomes) or chymotrypsin was dependent on both the equilibrium degree of swelling and the structure of the crosslinks (length of the oligopeptide sequence and structure of the amino acid residues). The release of the anticancer drug daunomycin imbibed in gels was pH-dependent, the rate of release being higher at lower pH. In addition, a gel was synthesized which contained a pentapeptide in the crosslinks and daunomycin bound via a tetrapeptide side-chain, and in this case, incubation with Tritosomes led to degradation with simultaneous release of the drug.