Polymeric controlled release of dexamethasone in normal rat brain

Carla S. Reinhard, Michael L. Radomsky, W. Mark Saltzman, John Hilton, Henry Brem

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Controlled release polymeric implants may improve delivery of anti-edema agents to the central nervous system. Ethylene-vinyl acetate copolymer (EVAc) matrices containing dexamethasone (35% w/w) were implanted either intracranially or intraperitoneally in Fisher 344 rats. Selective extraction and high performance liquid chromatography were used to quantify tissue concentrations after implantation of the drug-loaded polymer or intraperitoneal injection of an equivalent dose. Dexamethasone was detected in brain for up to 21 days after intracranial polymer implantation, with peak levels of 4.0 ± 0.7 ωg/g tissue measured in the ipsilateral hemisphere. Concentrations in the contralateral hemisphere and peripheral circulation were measurable for the first 12 h only (peak level at 1 h of 0.5 ± 0.2 ωg/g in the contralateral hemisphere). By contrast, intraperitoneal bolus administration of dexamethasone in control animals resulted in minimal brain levels (peak at 1 h of 0.8 ± 0.4 ωg/g) and very high plasma levels (peak at 4 h of 23.6 ± 6.0 ωg/g). No drug was detected in the brains of animals with intraperitoneal dexamethasone-EVAc implants. Measured dexamethasone concentrations were compared to a one-compartment pharmacokinetic model. The experimental results are best described by assuming diffusion-limited release of dexamethasone from the polymer (characteristic release constant of 0.5 ωg h- 1 2) and first order drug elimination (half-life of 16 h).

Original languageEnglish (US)
Pages (from-to)331-339
Number of pages9
JournalJournal of Controlled Release
Issue number3
StatePublished - Aug 1991


  • Brain edema
  • Controlled release
  • Dexamethasone
  • Pharmacokinetic modeling
  • Polymer
  • Targeted drug delivery

ASJC Scopus subject areas

  • Pharmaceutical Science


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