Gamma-aminobutyric acid loaded halloysite nanotubes and in vitro-in vivo evaluation for brain delivery
Özet
Gamma-aminobutyric acid (GABA) is a key neurotransmitter where it usually inhibits impulse transmission. GABA release blockage or postsynaptic reaction were determined to provoke epileptic convulsions. The aim of the present study was the development of brain-targeted, nanosized, nontoxic, biocompatible, highly specific formulations. Incorporation of GABA into halloysite nanotubes (HNT) was performed using different methods. Particle size, zeta potential and pH measurements, morphological, thermal, XRD, FTIR analyses and GABA quantification by validated HPLC method were used for the characterization of the systems prepared. Release pattern of GABA from the nanotubes was determined using a dialysis membrane. Following successful incorporation of GABA into HNTs for brain delivery, nanotube formulation coded HNT-GABA H1 was selected for in vivo studies. Smaller particle size with narrow size distribution, possible HNT-GABA interaction indicated by thermal, XRD and FTIR analyses and prolonged release were the parameters considered in this selection. Moreover, HNT-GABA H1 remained stable for 3-month storage period and showed higher cell viability values than GABA. Rats were used in in vivo studies and potential of anticonvulsant effect of GABA was determined in the pentylenetetrazole model of seizure. HNT-GABA H1 was found to increase latency of seizure, decrease ending time of the convulsion, duration of severe convulsion and mortality rate significantly compared to pure GABA. After administration of HNT-GABA H1, GABA concentration in Stratum corsatum measured by enzyme immune assay showed that it was not significantly higher than GABA administered alone. These findings suggest that GABA loaded HNTs reduces the duration of all phases of convulsion indicating efficient delivery of GABA to all brain areas to interfere with epileptic mechanism
