Poly(acrylamide-co-monoethyl Itaconate) Hydrog Devices for Cytarabine Release in Rats

Abstract

Abstract This study has tested the application of three different copolymeric poly(acrylamide-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 swelling at equilibrium in saline solution (NaCl, 0.9% w/w) was between 78 and 82% w/w, depending on the composition of the copolymer. The diffusion studies followed Fick’s second law. The diffusion coefficients for swelling of the gels were between 9.30 times 10−11 m2 s−1 and 37.42 times 10−11 m2 s−1; those for release of ara-C were between 3.42 times 10−11 m2 s−1 and 10.25 times 10−11 m2 s−1. The activation energies for swelling were in the range 16.60± 2.59-21.85± 1.78 kJ mol−1; those for ara-C release were 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 the plasma concentration of the drug was determined by high-performance liquid chromatography. The concentration of ara-C in plasma (range 17.67±5.68-10.76±2.15 μg mL−1) was maintained during the first stages (2–8 h) and no drug was detected after 32 h. This route of administration was compared with intraperitoneal injection of the drug. In conclusion, ara-C can be incorporated in hydrogels and released in a pharmacologically active form. The concentration of ara-C in plasma is maintained for long enough to improve therapeutic results.