Antiepileptic Drugs Encapsulated in Sol-Gel Titania Nanoparticles as Controlled Release System

Epilepsy is a serious neurological condition characterized by recurrent seizures. It is highly refractory to pharmacological treatment, with over one third of patients continuing to experience seizures despite taking multiple antiepileptic drugs (AEDs). Most of AEDs face difficulties in achieving penetration through the blood-brain barrier (BBB) and to reach to their target in the brain. Another problem with the treatment is the systemic side effects due to the presence of the drug in the blood circulation, often in much higher levels than in the brain. Due to this, alternative therapies are urgently required. One drug-delivery solution with demonstrated potential is an intracranial implantable device that is capable of releasing AEDs to the seizure focus directly over long time periods, for instance in rat brains. However, this approach would be clinically inappropriate. Implantation of the devices into patients with epilepsy would require invasive neurosurgical procedures that in themselves are not without risk. Intranasal delivery is emerging as a noninvasive option for delivering drugs to the central nervous system (CNS) with minimal peripheral exposure, avoiding side effects related to the AEDs. Additionally, this method facilitates the delivery of large (or charged) drugs, which fail to effectively cross the BBB. The high degree of vascularization and high permeability of nasal mucosa makes the nose a portal for drug delivery. Nanoparticles may offer an improvement to nose-to-brain drug delivery, since they are able to protect the encapsulated drug, from biological and/or chemical degradation, they cross the BBB that would increase availability of the drug in the brain but also release the drug in a controlled way.

Antiepileptic Drugs Encapsulated in Sol-Gel Titania Nanoparticles

Several means of delivery have been studied (nanoparticles, nanocapsules, nanotubes, micelles, microemulsions, liposomes) that represent a therapeutic alternative. Titania reservoirs synthesized by the sol-gel method for delivery of neurological drugs to the brain, have previously proved to be efficient for drug administration. Have been demonstrated that they are biocompatible, nontoxic and bioactive when implanted in the body. Administration of AEDs encapsulated within titania nanoparticles could have advantages like the ability to increase the solubility of poorly water soluble drugs (eg. carbamazepine, phenytoin, lamotrigine), improving its chemical stability and reducing drug-related side effects.

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