title: In vivo biocompatibility and in vitro characterization of poly-lactide-co-glycolide structures containing levetiracetam, for the treatment of epilepsy.
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.
authors: Department of Medicine, University of Melbourne, St. Vincent's Hospital, 35 Victoria Parade, Fitzroy, Victoria 3065, Australia; Clinical Neurosciences, 5th Floor, Daly Wing, St. Vincent's Hospital, 35 Victoria Parade, Fitzroy, Victoria 3065, Australia.
authors: Amy J
authors: AJ
authors: Halliday
authors: Toni E
authors: TE
authors: Campbell
authors: Joselito M
authors: JM
authors: Razal
authors: Karen J
authors: KJ
authors: McLean
authors: Timothy S
authors: TS
authors: Nelson
authors: Mark J
authors: MJ
authors: Cook
authors: Gordon G
authors: GG
authors: Wallace
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004827:Epilepsy / Q000188:drug therapy*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D000077287:Levetiracetam; D008297:Male; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D005904:Glial Fibrillary Acidic Protein; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077287:Levetiracetam; D010889:Piracetam