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

  • Gallardo A
  • Fernández F
  • Cifuentes A
 et al. 
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Abstract

Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of the immunosuppressor cyclosporine. Two copolymeric systems with copolymer compositions fVP=0.52 (namely VP-HEMA 60-40) and 0.42 (VP-HEMA 40-60) have been prepared and tested in vitro and in vivo using rats as animal model. Micellar 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 the in vitro release of the drug (with time profiles from a few days to several weeks for the VP-HEMA 60-40 and 40-60, respectively) and the in vivo response that correlates with the previous in vitro results: the more hydrophobic implant (VP-HEMA 40-60) reverts the immune response more slowly (2-4 weeks) compared to the more hydrophilic one (VP-HEMA 60-40, 1-2 weeks). © 2001 Elsevier Science B.V.

Author-supplied keywords

  • 2-Hydroxyethyl methacrylate
  • Copolymers
  • Cyclosporine
  • Vinylpyrrolidone

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