Kinetic study of controlled release of VPA and DPH antiepileptic drugs using biocompatible nanostructured sol–gel TiO2

Sol–gel TiO2 porous matrix was used to host valproic acid (VPA) and phenytoin (DPH), which are commonly used as antiepileptic drugs. The addition of these drugs was carried out during the synthesis in the hydrolysis stage. In vitro short term kinetic studies on drug liberation showed that almost all samples followed a first order kinetics with the exception of one sample which had a linear behavior. High resolution electron microscopy revealed the existence of nanocrystalinity in all samples, however, electron diffraction patterns showed that some were predominantly amorphous while in others suggested a greater density of nanocrystals. NMR studies demonstrated that VPA was less mobile in a more crystalline TiO2 matrix than when the TiO2 is mainly amorphous. Some features of the kinetics of drug liberation are explained in terms of the competition between nanocrystallinity and drug content. The reservoirs were implanted by means of stereotactic surgery in Wistar rats in which epilepsy was previously induced following the Kindling model of epilepsy. The efficiency of the reservoirs was follow by electroencephalography (EEGs). In vivo studies revealed that a more crystalline sample was more effective in preventing further epileptic events than samples with a higher content of VPA but predominantly amorphous.