Development of a nanosized drug delivery system interfering epileptic mechanism and evalution of its in vivo behaviour

Epilepsy is one of the most common neurological diseases worldwide. Generalized or paroxysmal focal reaction of brain is called "epilepsy". A number of study is being performed on epilepsy. In those studies, inhibition of γ-aminobutyric acid (GABA) synthesis, blockage of release or postsynaptic reaction were determined to provoke convulsions. Decrease in GABA concentrations was seen cerebrospinal fluid with GABA concentrations in brain nerve terminals, febrile convulsions and patients resistant to epilepsy treatment. It was also reported that convulsion, coma and even death can be observed by means of reduction in the concentration of GABA. Even though there are different approaches for the treatment of epilepsy, in this study incorporation of GABA into unique polymeric nanoparticles (PNP) prepared with reverse emulsion polymerization method and halloysite nanotubes (HNT) was aimed depending on the most recent theory related to GABA. In other words, development of brain-targeted, nanosized, nontoxic, biocompatible, highly specific and high affinity formulations was aimed by using unloaded/loaded PNP and HNT drug delivery systems. Characterization studies of formulations were performed by particle size and distribution, zeta potential, particle shape and surface properties, physical appearance, thermal, x-ray diffraction (XRD), infrared (IR), determination of the amount of active agent analyses. In vitro cytotoxicity and in vivo animal studies were performed on formulations selected considering characterization and in vitro analyses results. In the in vivo studies achieved on epileptic rat induced by pentylenetetrazole (PTZ), phosphate buffer (pH 7.4) (PBS), GABA and PNP and HNT formulations containing GABA were applied on experimental groups. After 4 hours of injections, PTZ was injected intraperitoneally (i.p.) and convulsions were generated. Rats were monitored for 30 minutes and were evaluated by scoring. After this monitorization period, brains were removed and Stratum Corsatum were isolated, homogenized and GABA levels were determined by enzyme-linked immunosorbent assay (ELISA) kit. According to the data obtained from the comparison of drug delivery systems prepared with GABA and PBS, significant changes in latency, total convulsion period, severe convulsion period and mortality of rats were demonstrated by statistical analyses. Amount of GABA analyzed by enzyme immune assay analyzer was increased considerably for PNP-29. As a result, drug delivery systems ensuring transportation of the endogen compound GABA to the brain could be prepared regarding in vitro and in vivo analyses results.