In vitro/in vivo evaluation of gamma-aminobutyric acid-loadedN,N-dimethylacrylamide-based pegylated polymeric nanoparticles for brain delivery to treat epilepsy.
Objectives of this study were the delivery of gamma aminobutyric acid (GABA) into the brain by means of developing brain targeted, nanosized, non-toxic and biocompatible polymeric nanoparticles, and investigating their effectiveness in epilepsy. For this purpose, GABA conjugated N,N-dimethylacrylamide-based pegylated nanoparticles were designed and characterised for particle size, zeta potential, pH, morphology, DSC, XRD, FTIR, GABA quantification and in vitro release. Formulations showed smaller particle size, cationic zeta potential characteristic, possible GABA polymeric matrix interaction and prolonged release pattern. Brain responses were examined using epileptic rats. Both formulations prepared were found to increase latency of seizure, decrease ending time of convulsion, duration of severe convulsion and mortality rate significantly compared with GABA solution. When GABA concentration was measured in Stratum corsatum, there was no statistical difference between GABA solution and formulations. All findings suggested enhancement in all phases of seizures indicating efficient delivery of GABA into the brain via formulations.
a Department of Pharmaceutical Technology , Anadolu University , Eskişehir , Turkey.
Gülsel
G
Yurtdaş Kırımlıoğlu
b Faculty of Engineering and Natural Sciences , Sabancı University , İstanbul , Turkey.
Yusuf
Y
Menceloğlu
c Department of Pharmacology , Osmangazi University , Eskişehir , Turkey.
Kevser
K
Erol
a Department of Pharmaceutical Technology , Anadolu University , Eskişehir , Turkey.
Yasemin
Y
Yazan
D000178:Acrylamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
D000178:Acrylamides; D011092:Polyethylene Glycols; D005680:gamma-Aminobutyric Acid; C099046:N,N-dimethylacrylamide; C000595209:polyethylene glycol 1000
Gamma-aminobutyric acid; epilepsy; pegylated polymeric nanoparticles; pharmacodynamics; stability