NOVEL BIODEGRADABLE HYDROGELS PREPARED USING THE DIVINYLIC CROSS-LINKING AGENT N,O-DIMETHACRYLOYLHYDROXYLAMINE .1. SYNTHESIS AND CHARACTERIZATION OF RATES OF GEL DEGRADATION, AND RATE OF RELEASE OF MODEL-DRUGS, INVITRO AND INVIVO

Hydrophilic gels based on copolymers of A-(2-hydroxypropyl)methacrylamide and N,O-dimethacryloylhydroxylamine were synthesized, and the hydrolytic stability of these gels was studied in buffers with a pH range 2-8. The hydrogels were stable at acidic pH (below 5), but were hydrolysed at neutral and mild alkaline pH. The rate of hydrolysis depended on the pH of the solution and on the crosslinking density of the gel. The in vivo rate of gel hydrolysis correlated with in vitro data. The potential of hydrogels as novel drug release systems was investigated with methotrexate, 5-fluorouracil, doxorubicin and polymer-bound doxorubicin as model drugs. The rate of drug release was studied in vitro and data obtained for targetable and nontargetable polymeric conjugates of doxorubicin in vitro was compared with the kinetics of release measured in vivo in mice.