Modulated release of cyclosporine from soluble vinyl pyrrolidone-hydroxyethyl methacrylate copolymer hydrogels - A correlation of 'in vitro' and 'in vivo' experiments

Soluble uncrosslinked and high molecular weight copolymers of vinlypyrrolid one, VP, with 2-hydroxyethyl methacrylate, HEMA prepared by free radical co polymerization, are proposed as supports for the modulated release of the i mmunosuppressor cyclosporine. Two copolymeric systems with copolymer compos itions f(VP) = 0.52 (namely VP-HEMA 60-40) and 0.42 (VP-HEMA 40-60) have be en prepared and tested in vitro and in vivo using rats as animal model. Mic ellar electrokinetic capillary chromatography, MEKC, has been used for the simultaneous detection of the polymer reabsorption and the drug release for the in vitro experiments. The composition and microstructural distribution of the copolymer system controls the solubilization rate which modulates t he in vitro release of the drug (with time profiles from a few days to seve ral weeks for the VP-HEMA 60-40 and 40-60, respectively) and the in vivo re sponse that correlates with the previous in vitro results: the more hydroph obic implant (VP-HEMA 40-60) reverts the immune response more slowly (2-4 w eeks) compared to the more hydrophilic one (VP-HEMA 60-40, 1-2 weeks). (C) 2001 Elsevier Science B.V. All rights reserved.