In vivo biocompatibility and in vitro characterization of poly-lactide-co-glycolide structures containing levetiracetam, for the treatment of epilepsy

J Biomed Mater Res A. 2012 Feb;100(2):424-31. doi: 10.1002/jbm.a.33208. Epub 2011 Nov 21.

Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is highly resistant to medication with up to 40% of patients continuing to experience seizures whilst taking oral antiepileptic drugs. Recent research suggests that this may be due to abnormalities in the blood-brain barrier, which prevent the passage of therapeutic substances into the brain. We sought to develop a drug delivery material that could be implanted within the brain at the origin of the seizures to release antiepileptic drugs locally and avoid the blood brain barrier. We produced poly-lactide-co-glycolide drop-cast films and wet-spun fibers loaded with the novel antiepileptic drug Levetiracetam, and investigated their morphology, in vitro drug release characteristics, and brain biocompatibility in adult rats. The best performing structures released Levetiracetam constantly for at least 5 months in vitro, and were found to be highly brain biocompatible following month-long implantations in the motor cortex of adult rats. These results demonstrate the potential of polymer-based drug delivery devices in the treatment of epilepsy and warrant their investigation in animal models of focal epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Brain / drug effects
  • Brain / pathology
  • Epilepsy / drug therapy*
  • Glial Fibrillary Acidic Protein / metabolism
  • Lactic Acid / chemistry*
  • Levetiracetam
  • Male
  • Materials Testing*
  • Microscopy, Electron, Scanning
  • Piracetam / analogs & derivatives*
  • Piracetam / pharmacology
  • Piracetam / therapeutic use
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Anticonvulsants
  • Glial Fibrillary Acidic Protein
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Levetiracetam
  • Piracetam