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Electro-responsive hydrogel nanoparticles for controlled release of anti-epileptic drugs

摘要Objective: Epilepsy is one of the most prevalent neurological disorders.For most patients antiepileptic drugs are the mainstay of the management of epilepsy.Epileptic seizure is the paroxysmal abnormalities synchronization electrical activity in brain neurons.Therefore, constraining the discharge of epilepsy in the local site and suppressing it timely is the key to prevent the seizure.The aim of this study was to prepare and characterize the electro-responsive hydrogel nanoparticles (ERHNPs) based on 2-(Dimethylamino) Ethyl methacrylate (DMAEMA).Methods: The electro-responsive hydrogel nanoparticles were prepared by soap-free emulsion polymerization.DMAEMA, Ethenylbenzene (ST) and Sodium 4-vinylbenzenesulfonate (NaSS) were used as monomers.N,N'-Methylene bisacrylamide (BIS) was used as crosslinker.Using phenytoin sodium (PHT) as a model drug, PHT-loaded ERHNPs was prepared by ERHNPs soaked into a concentrated drug solution and followed by lyophilized.The physicochemical properties of the ERHNPs such as number average diameter, drug encapsulation efficiency and in vitro drug release were investigated.The diameters of ERHNPs were also determined under the DC electric field with 50-500μA.PHT release profiles in vitro were also evaluated in the presence of an external electric field with DC current of 100μA.Results: The ERHNPs were successfully synthesized with the yields of 50-70%.ERHNPs had a number average diameter of 50-120nm.The drug encapsulation efficiency could reach up to 85%.In vitro PHT release demonstrated the sustained release of PHT, and could be prolonged to 24h.In the presence of an external electric field with DC current of 100μA, more PHT released was determined at the same points.The increased number average diameter of ERHNPs was observed with the increasing current under the DC electric field with 50-500μA.Coclusions: The hydrogel nanoparticles based on DMAEMA had a good electric field response.And at the beginning of the seizure, the ERHNPs will convert the electrical energy into mechanical energy immediately, which weaken the epileptiform discharges and release drug quickly leading to an efficient treatment of epilepsy.The electro-responsive hydrogel nanoparticles will be a potential drug delivery system for epilepsy treatment.

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