Send Orders for Reprints to reprints@benthamscience.net Current Drug Metabolism, 2014, 15, 000-000 1 1389-2002/14 $58.00+.00 © 2014 Bentham Science Publishers A Synopsis of Nano-Technological Approaches Toward Anti-Epilepsy Therapy: Present and Future Research Implications Nasimudeen R. Jabir 1 , Shams Tabrez 1 , C. K. Firoz 1 , Syed Kashif Zaidi 2 , Saleh S. Baeesa 3 , Siew Hua Gan 4 , Shazi Shakil 5 , Mohammad Amjad Kamal 1,6* 1 King Fahd Medical Research Center; 2 Center of Excellence in Genomic Medicine Research; 3 Division of Neurosurgery, College of Medicine [King Abdulaziz University, Jeddah, Saudi Arabia]; 4 Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia; 5 Department of Bio-Engineering, Integral University, Lucknow, 226026, In- dia; 6 Enzymoic, 7 Peterlee Place, Hebersham, NSW 2770, Australia Abstract: Epilepsy is a non-communicable central nervous system disorder that affects over 60 million people worldwide. The existing developments in epilepsy treatment face major hurdles due to drug resistance and disease recurrence after reduction of medication. Nano- technological anti-epileptic drug (AED) delivery systems have recently garnered attention due to their ability to cross the blood brain bar- rier, improved selectivity and potential for sustained drug delivery to the brain. This review focuses on several nano-based AED delivery systems, including liposomes, nano-emulsions, polymeric nanoparticles, solid-lipid nanoparticles and magnetic nanoparticles. Their limi- tations and future prospects in terms of AED delivery to the brain are also highlighted. It is hoped that the present communication is help- ful in the identification of potential AED delivery systems based on their advantages and disadvantages. Keywords: Epilepsy, liposomes, nano-emulsions, polymeric nanoparticles, solid-lipid nanoparticles, magnetic nanoparticles, therapy INTRODUCTION Epilepsy is a non-communicable central nervous system (CNS) disorder in which an enormous increase in electrical impulses oc- curs in one focal locus of the brain and/or the entire brain, leading to partial or generalized seizures. Abnormal and drastic neuronal excitation may lead to physical and mental benign ailments and serious co-morbidities. Over 60 million people worldwide are af- fected with epilepsy [1]. Despite developments in epilepsy treat- ment, the quality of life of patients suffering from this disorder remains poor. A major hurdle is drug resistance and epilepsy recur- rence after reduction of medication [2]. Most anti-epileptic drugs (AED) are administered orally or intravenously. Up to 40% of pa- tients develop drug resistance at later stages of treatment [3, 4], resulting in uncontrolled seizures, a higher risk of brain damage and increased mortality rates [5]. Patients experience emotional and behavioral changes, seizures, convulsions, muscular spasms, de- pression and, in some cases, unconsciousness [6]. Drug-resistant epilepsy is a formidable health issue. Drugs for epilepsy suffer from poor bioavailability and eventually become ineffective over the course of treatment due to drug resistance [7]. Epilepsy treatment is often complicated due to the inability of available AEDs to cross the adjunctive blood brain barrier (BBB), which could be overcome through appropriate drug delivery sys- tems. The ideal system would provide localized and controlled release of AEDs to targeted sites in the brain to help reduce drug- associated toxicities and enhance the efficacy of the drugs. Several strategies for the effective delivery of AEDs have been reported in the scientific literature. Nanotechnology-based systems appear to be a promising and innovative development. Several nanostructure drug delivery carriers have recently been reported as an effective *Address correspondence tothis author at the King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia; Tel: 02-98644812; Fax: + 15016368847; E-mail: meu.fabg@hotmail.com CNS delivery systems to overcome the problem of AED elimina- tion at the BBB and result in increased persistence of drugs [7]. Nanotechnology-based medicine (nano-medicine) refers to the surface property characterization and design of nano-carriers for various medicinal strategies [8, 9]. Therapeutic agents are embed- ded into or coated onto nano-carriers, small colloidal or compact structural platforms ranging in size from a 1 to 1000 nm [2, 10]. These nano-platforms (NPs) readily interact with the cellular envi- ronment at the molecular level to produce the desired physiological response. Nanotechnology-based AEDs have recently garnered attention because of their ability to cross the BBB, improved selec- tivity and potential for sustained drug delivery to the brain [11]. The size, molecular weight, co-polymer ratio, mechanism of ero- sion and surface charge are important factors when considering the effectiveness of NPs. For example, the size of the NPs is a very important determinant for its efficiency in crossing the BBB; NPs ranging from 35 to 64 nm easily access most neural tissues [12]. Size-specific NPs synthesis could be achieved through different preparation methods. As a result of the reduction in the sizes of NPs, the nano-carrier system presents a large surface area that can carry large dosages of drugs, efficiently decrease the peripheral toxicity of drugs, and provide adequate delivery of drugs to their targets [7]. The surface charge of NPs is also an important factor in determining their efficiency in brain targeting. It has been reported in the literature that neutral and mildly negatively charged NPs are more effective than positively charged NPs. On the other hand, positively charged NPs are able to make immediate alterations in the BBB (albeit for shorter durations) and are later eliminated by the reticulo-endothelial system (RES) [13, 14]. Different approaches have been used in the pursuit of potential nano-carriers for AED delivery towards brain-specific sites. Evi- dence indicates that there are pathological alterations in the perme- ability of the BBB in patients with epilepsy. Various nano-carriers may be able to easily access targeted brain sites by manipulating the