Injectable phenytoin loaded polymeric microspheres for the control of temporal lobe epilepsy in rats.
OBJECTIVE
Epilepsy is a prevalent neurological disorder with a high frequency of drug resistance. While significant advancements have been made in drug delivery systems to overcome anti-epileptic drug resistance, efficacies of materials in biological systems have been poorly studied. The purpose of the study was to evaluate the anti-epileptic effects of injectable poly(epsilon-caprolactone) (PCL) microspheres for controlled release of an anticonvulsant, phenytoin (PHT), in an animal model of epilepsy.


METHODS
PHT-PCL and Blank-PCL microspheres formulated using an oil-in-water (O/W) emulsion solvent evaporation method were evaluated for particle size, encapsulation efficiency, surface morphology and in-vitro drug release profile. Microspheres with the most suitable morphology and release characteristics weresubsequently injected into the hippocampus of a rat tetanus toxin model of temporal lobe epilepsy. Electrocorticography (ECoG)from the cerebral cortex were recorded for all animals. The number of seizure events, severity of seizures, and seizure duration were then compared between the two treatment groups.


RESULTS
We have shown that small injections of drug-loaded microspheres are biologically tolerated and released PHT can control seizures for the expected period of time that is in accord with in-vitro release data.


CONCLUSIONS
The study demonstrated the feasibility of polymer-based delivery systems incontrolling focal seizures.
St Vincent's Department of Medicine, University of Melbourne, Fitzroy, VIC, Australia.|Centre for Clinical Neurosciences and Neurological Research, St. Vincent's Hospital Melbourne, Fitzroy, VIC, Australia.
Jonathan L
JL
Jiang
Intelligent Polymer Research Institute and ARC Centre of Excellence for Electromaterials Science, AIIM Facility, Innovation Campus, University of Wollongong, Wollongong, NSW, Australia.
Zhilian
Z
Yue
Faculty of Veterinary Science, University of Melbourne, 250 Princes Hwy, Werribee, VIC, Australia.
Sebastien H
SH
Bauquier
St Vincent's Department of Medicine, University of Melbourne, Fitzroy, VIC, Australia.
Alan
A
Lai
Intelligent Polymer Research Institute and ARC Centre of Excellence for Electromaterials Science, AIIM Facility, Innovation Campus, University of Wollongong, Wollongong, NSW, Australia.
Yu
Y
Chen
St Vincent's Department of Medicine, University of Melbourne, Fitzroy, VIC, Australia.|Centre for Clinical Neurosciences and Neurological Research, St. Vincent's Hospital Melbourne, Fitzroy, VIC, Australia.
Karen J
KJ
McLean
St Vincent's Department of Medicine, University of Melbourne, Fitzroy, VIC, Australia.
Amy J
AJ
Halliday
Department of Neurology, Shenyang First People's Hospital, Shenyang, Liaoning, China (PRC).
Yi
Y
Sui
Intelligent Polymer Research Institute and ARC Centre of Excellence for Electromaterials Science, AIIM Facility, Innovation Campus, University of Wollongong, Wollongong, NSW, Australia.
Simon
S
Moulton
Intelligent Polymer Research Institute and ARC Centre of Excellence for Electromaterials Science, AIIM Facility, Innovation Campus, University of Wollongong, Wollongong, NSW, Australia.
Gordon G
GG
Wallace
St Vincent's Department of Medicine, University of Melbourne, Fitzroy, VIC, Australia.|Centre for Clinical Neurosciences and Neurological Research, St. Vincent's Hospital Melbourne, Fitzroy, VIC, Australia.
Mark J
MJ
Cook
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D000069280:Electrocorticography; D004833:Epilepsy, Temporal Lobe / Q000188:drug therapy* / Q000503:physiopathology; D005240:Feasibility Studies; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008863:Microspheres; D010316:Particle Size; D010672:Phenytoin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology; D013499:Surface Properties; D013744:Tetanus Toxin; D016896:Treatment Outcome
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D011091:Polyesters; D013744:Tetanus Toxin; C016240:polycaprolactone; D010672:Phenytoin
Biodegradable; drug delivery; epilepsy; microspheres; phenytoin; polymer