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The use of drug nanocarriers in pharmacoresistant epilepsy is potentially a very useful tool that can be applied to overcome the drug delivery problem. Developing this technology requires a multidisciplinary approach involving the collaborative work of nanotechnology and pharmacology specialists.
However, development of these models requires prolonged experimental periods and low (20 percent or less) percentage of pharmacoresistant subjects obtained (127). Repeated administration of 3-mercaptopropionic acid or pentylentetrazol (47, 128) is a short-term alternative for obtaining animals with overexpression of brain transporters. These procedures however do not induce spontaneous seizure.
Other significant criteria to be considered in the production of nano-sized carriers for AEDs as therapeutic options for pharmacoresistant epilepsy include: 1) nanosystems must be engineered in such a way that AEDs can be masked and bypass the effects of multi-resistant proteins on the BBB that enable penetration into brain parenchyma 2) nanosystems must lead to successful prism.
Among the various types of nanosystems currently evaluated, MnPs have proven to be one of the best strategies for different biomedical uses, such as MRI contrast agents, cell therapy, tissue repair, hyperthermia ablation, drug delivery and carrier systems (140-142). MnPs offer special advantages such as their small size (< 100nm) in addition to their easy and economical synthesis process Suitable for cell membrane penetration (114, 143). Their biodegradability is performed by lysosomal rupture of the iron oxide core resulting in iron ions that are incorporated back into the hemoglobin pool (144) Given the magnetic characteristics of MnPs, intracerebral release from special devices may be controlled by magnetic fields (145) Some reports indicate that MnPs are highly biocompatible and do not induce toxic effects from their administration (146-148). MnPs may represent an excellent strategy for delivering AEDs into the brain parenchyma of patients with pharmacoresistant epilepsy according to this research. Indeed, a previous study indicates that 4 weeks of intraperitoneal administration of MnPs is not producing 'apparent' toxicity, Histopathological changes or adverse effects on the development and conduct of the body (149) However, it is necessary to note that MnPs in the biological environment are also reactive and can cause chemical interactions and toxicological effects (150, 151). On this issue, the MnPs are described as being able to Produce excessive reactive oxygen species, a situation which can result in oxidative stress (152, 153), neuronal damage, proinflammatory effects and BBB permeability modifications (154). Oxidative stress can cause cell death due to damage to the mitochondrial membrane or a malfunction of the electron chain (150, 155), Mutagenesis (156), activation of oncogenes such as Ras (157) or production of end-products detrimental to DNA (158) and subsequent cancer (159). Therefore it is important to determine whether adverse effects are produced after chronic administration of MnPs under different physiological conditions.
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