3563 Nanomedicine (Lond.) (2015) 10(24), 3563–3577 ISSN 1743-5889 part of Research Article 10.2217/nnm.15.173 © 2015 Future Medicine Ltd Aim: The present study was focused to evaluate the anticonvulsant effects of phenytoin (PHT) loaded in the silica core of iron oxide nanoparticles (NPs) in an animal model with pharmacoresistant seizures. Materials & methods: PHT-loaded NPs were synthesized and characterized. The anticonvulsant effects of PHT-loaded NPs were investigated in rats with pharmacoresistant seizures associated with brain P-glycoprotein (P-gp) overexpression. Results & conclusion: In P-gp-overexpressing rats, administration of PHT-loaded NPs resulted in reduced prevalence of clonus (40% p < 0.05) and tonic–clonic seizures (20%; p < 0.02). These effects were not evident when animals were treated with PHT not loaded in the NPs. The results obtained support the notion that NPs can be used as drugs carriers to the brain with pharmacoresistant seizures. Keywords:฀blood–brain฀barrier฀•฀nanoparticles฀•฀neuronal฀excitability฀•฀P-glycoprotein฀ •฀pharmacorresistance฀•฀phenytoin Background The International League Against Epilepsy defined pharmacoresistant epilepsy as the ‘failure of adequate trials of two tolerated and appropriately chosen and used antiepi- leptic drugs (AEDs) schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom’ [1] . Approximately a third of the patients with epilepsy are diag- nosed as drug resistant [2] . Psychiatric, psy- chological, emotional, economic and social impairments are some of the repercussions of pharmacoresistant epilepsy, in addition to a greater risk of sudden unexpected death and suicide [3–5] . Different therapeutic strategies have been developed to manage pharmacoresis- tant epilepsy. For example, epilepsy surgery and neuromodulation occasionally result in total remission of seizures [6–9] . Neverthe- less, these procedures have been associated with adverse effects such as hemorrhage and infections [10–13] . Moreover, these are expen- sive procedures, and not all patients fulfill the criteria to be treated with any of these therapeutic strategies [14] . Pharmacoresistant epilepsy has been pro- posed to result from an increased expression of drug transporters, such as P-glicoprotein (P-gp), at the luminal side of the blood– brain barrier (BBB) [15,16] . This augmented expression of P-gp limits the penetration of AEDs into the brain [17–20] , an effect that can be avoided with the administration of P-gp blockers [21,22] . Although P-gp inhibitors might be useful for overcoming drug refrac- toriness, the low specificity of these inhibitors and/or their prolonged use could affect the pharmacokinetics of other drugs, and may exert pharmacodynamic adverse effects and toxicity [23,24] . Nanoparticles (NPs) have been receiving significant attention for their therapeutic and diagnostic applications. Some of the charac- teristics that make them attractive are their small size, high stability, ability to overcome organ barriers such as BBB and their bio- compatibility [25–27] . NPs have been used as drug carriers for AEDs and anticonvulsant drugs in animal models of seizures [28–34] . Nevertheless, at present there are no studies that determine the effects of AEDs trans- Phenytoin carried by silica core iron oxide nanoparticles reduces the expression of pharmacoresistant seizures in rats Argelia Rosillo-de la Torre 1 , Lizbeth Zurita-Olvera 2 , Sandra Orozco-Suárez 3 , Perla E Garcia Casillas 4 , Hermelinda Salgado-Ceballos 3 , Gabriel Luna-Bárcenas* ,2 & Luisa Rocha** ,1 1 Department฀of฀Pharmacobiology,฀Center฀ of฀Research฀&฀Advanced฀Studies,฀Calz.฀ de฀los฀Tenorios฀No.฀235.฀Col.฀Granjas฀ Coapa,฀14330,฀Tlalpan,฀DF฀Mexico 2 Polymer฀&฀Biopolymer฀Research฀Group,฀ Center฀of฀Research฀&฀Advanced฀Studies,฀ Querétaro฀Unit,฀Libramiento฀Norponiente฀ #2000,฀Fracc.฀Real฀de฀Juriquilla,฀76230,฀ Queretaro,฀Mexico 3 Unit฀for฀Medical฀Research฀in฀ Neurological฀Diseases,฀National฀ Medical฀Center,฀Av.฀Cuauhtémoc฀330.฀ Col.฀Doctores,฀06720,฀Cuauhtémoc,฀ DF฀Mexico 4 Institute฀of฀Engineer฀&฀Technology,฀ Autonomus฀University฀of฀Juarez฀City,฀ Av.฀del฀Charro฀no.฀450฀Nte.฀Col.฀Partido฀ Romero,฀32310,฀Juarez฀City,฀Chihuahua,฀ Mexico *Author฀for฀correspondence:฀ gluna@qro.cinvestav.mx **Author฀for฀correspondence: lrocha@cinvestav.mx฀ For reprint orders, please contact: reprints@futuremedicine.com