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.

Evaluation of the Biocompatibility of Polypyrrole Implanted Subdurally in GAERS

“…NeuN/GFAP staining was performed similarly to previously published protocol . In brief, immediately after taking the slices out of the freezer, they were placed into RT 10% NBF for 15 min.…”

“…H&E stained sections were evaluated to assess macroscopic consequences of polymer implantation. The degree of damage was rated following a published scale: minor = incomplete disruption of the meninges and disruption of molecular cortical layer; moderate = complete disruption of the meninges and molecular cortical layer; severe = damage extending beyond the meninges and molecular cortical layer . Immunohistochemically stained sections were subjectively rated from 0 to 3 (0 = no change in immunoreactivity, 1 = subtle changes in immunoreactivity, 2 = clear changes in immunoreactivity but only affecting a very limited part of the cortex, 3 = clear changes in immunoreactivity affecting an extended area of the cortex).…”

“…The results of this study indicated that drug‐eluting poly( d , l ‐lactide‐co‐glycolide) (PLGA) polymer implants represents a promising evolving treatment option for intractable epilepsy. The PLGA polymers used is a biodegradable copolymer that is very well tolerated by the brain . However this polymer can only be used as a passive release vehicle.…”

Antiepileptic Effects of Lacosamide Loaded Polymers Implanted Subdurally in GAERS

“…Poly(D,L-lactide-co-glycolide) (PLGA) is the most commonly used biodegradable polymer as it is highly biocompatible and easily engineered and has been approved for drug delivery purposes by the United States Food and Drug Administration [10]. It has been used in numerous applications including bone and skin tissue engineering, ocular treatment, vaccine, cancer therapy, and nerve regeneration [11][12][13][14][15].…”

“…It has been used in numerous applications including bone and skin tissue engineering, ocular treatment, vaccine, cancer therapy, and nerve regeneration [11][12][13][14][15]. PLGA polymers have also been successfully used for intracranial drug delivery in animal models of neurological disorders, showing no evidence of toxic injury or immunemediated inflammation when implanted subdurally above the motor cortex in rats [10].…”