Slow releasing of ara-C from poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-N-vinyl-2-pyrrolidone) hydrogels implanted subcutaneously in the back of rats

The release of cytarabine (ara-C) from poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-N-vinyl-2-pyrrolidone) hydrogels cross-linked with different amounts of ethyleneglycol dimethacrylate (EDGMA) ‘in vivo’ has been studied. Two ara-C loaded hydrogel discs, each with 25 mg of the drug, were subcutaneously implanted in the back of male Wistar rats. Total ara-C dose was 230 mg kg−1. Ara-C and ara-U plasmatic concentration were determined by HPLC. Periods of constant drug concentration are observed from all gels. Ara-C concentrations in the steady-state are between 19.0 ± 2.0 and 2.2 ± 0.8 μmol l−1. The release time of ara-C was between 3 days from pHEMA 0.5% and 16 days from H80/VP20/E15 gels. These results are very different of that obtained when ara-C is administered by intraperitoneal injection, in this case peaks of maximum concentration (between 24 ± 1 and 3.9 ± 0.4 μg ml−1) 30 min after the injection are originated, and no drug is detected 4 h after the injection.