Poly(acrylamide-co-monoethyl itaconate) hydrogels as devices for cytarabine release in rats

This study has tested the application of three different copolymeric poly(a crylamide-comonoethyl itaconate; A/MEI) hydrogels, 90A/10MEI, 75A/25MEI and 60A/40MEI, on the release of cytarabine (ara-C). The drug was incorporated in gels by placing it in the polymerization feed mixture and discs loaded with 5-50 mg ara-C were obtained. The amount of sw elling at equilibrium in saline solution (NaCl, 0.9% w/w) was between 78 an d 82% w/w, depending on the composition of the copolymer. The diffusion stu dies followed Fick's second law. The diffusion coefficients for swelling of the gels were between 9.30 x 10(-11) m(2) s(-1) and 37.42 x 10(-11) m(2) s (-1) those for release of ara-C were between 3.42 x 10(-11) m(2) s(-1) and 10.25 x 10(-11) m(2) s(-1). The activation energies for swelling were in th e range 16.60 +/- 2.59-21.85 +/- 1.78 kT mol(-1) those for ara-C release we re 28.13 +/- 3.1-29.7 +/- 4.6 kJ mol(-1) To determine the applicability of these copolymers, 75A/25MEI gel was subcutaneously implanted in rats and th e plasma concentration of the drug was determined by highperformance liquid chromatography. The concentration of ara-C in plasma (range 17.67+/-5.68-1 0.76 +/-: 2.15 mu g mL(-1)) was maintained during the first stages (2-8 h) and no drug was detected after 32h. This route of administration was compar ed with intraperitoneal injection of the drug. In conclusion, ara-C can be incorporated in hydrogels and released in a pha rmacologically active form. The concentration of ara-C in plasma is maintai ned for long enough to improve therapeutic results.