Cytarabine trapping in poly(2-hydroxyethyl methacrylate-co-acrylamide) hydrogels: drug delivery studies

Copolymeric hydrogels of poly(2-hydroxyethyl methacrylate-co-acrylamide) [p (HEwMA-co-A)] crosslinked with ethylene glycol dimethacrylate, with a high equilibrium degree of swelling (37-65w%) in saline solution (NaCl 0.9wt%) w ere synthesized as devices for controlled release of cytarabine (ara-C). Tw o compositions of the copolymer, each with a different degree of crosslinki ng have been studied, HEMA80/A20 and HEMA60/A40. The antineoplasic drug was included in the feed mixture of polymerization, and discs 3.7 +/- 0.4mm th ick and 11.8 +/- 0.2mm in diameter with 5-40mg (1.0-8.3 wt%) of ara-C were obtained. The diffusion studies followed Fick's second law. The diffusion c oefficients for swelling of the gels were between 3.60 x 10(-11) and 15.8 x 10(-11)m(2)s(-1): those for release of ara-C were between 0.31 x 10(-11) a nd 7.18 x 10(-11) m(2) s(-1). The activation energies for swelling were in the range 23.4-31.9kJ mol(-1) and those for ara-C release were 42.2-61.6kJ mol(-1); their values indicate that the drug release process depends on dru g-matrix and drug-water interactions that are influenced by the aqueous sol ution content and the network size of the gels. Total release of the drug t akes place between 17h from H60/A40/E2 at 310 K and 6 days from H80/A20/E10 at 288 K. Ara-C degradation was not observed either during loading of the gels or during drug release. (C) 1999 Society of Chemical Industry.