A Synopsis of Nano-Technological Approaches Toward Anti-Epilepsy Therapy: Present and Future Research Implications.

Epilepsy is a non-communicable central nervous system disorder that affects over 60 million people worldwide. The developments in epilepsy treatment face major hurdles due to drug resistance and disease recurrence after reduction in medication. Nano-technological anti-epileptic drug (AED) delivery systems have recently garnered attention due to their ability to cross the blood brain barrier, 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 limitations and future prospects in terms of AED delivery to the brain are also highlighted. It is hoped that the present communication will be helpful in the identification of potential AED delivery systems based on their advantages and disadvantages.

[1]  Senshang Lin,et al.  Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration , 2014, Pharmaceutical development and technology.

[2]  Z. Afawi Clinical and Genetic Aspects of Epilepsy , 2014 .

[3]  C. Perou,et al.  Pharmacokinetics and Efficacy of PEGylated Liposomal Doxorubicin in an Intracranial Model of Breast Cancer , 2013, PloS one.

[4]  Seemalata Jain,et al.  Liposomal formulation of curcumin attenuates seizures in different experimental models of epilepsy in mice , 2013, Fundamental & clinical pharmacology.

[5]  Vladimir P. Torchilin,et al.  Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting , 2013, Journal of drug delivery.

[6]  N. Mody,et al.  Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain , 2013, Journal of Nanoparticle Research.

[7]  Mohammad Hassan Khalid,et al.  Nanoneurotoxicity to Nanoneuroprotection Using Biological and Computational Approaches , 2013, Journal of Environmental Science And Health Part C - Environmental Carcinogenesis & Ecotoxicology Reviews.

[8]  M. Kamal,et al.  Cancer Chemoprevention by Polyphenols and Their Potential Application as Nanomedicine , 2013, Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews.

[9]  Josemir W Sander,et al.  Phenobarbital: missing in action. , 2012, Bulletin of the World Health Organization.

[10]  M. Rossi Targeting Anti-Epileptic Drug Therapy without Collateral Damage: Nanocarrier-Based Drug Delivery , 2012, Epilepsy currents.

[11]  Y. Chen,et al.  Design and characterization of a novel amphiphilic chitosan nanocapsule-based thermo-gelling biogel with sustained in vivo release of the hydrophilic anti-epilepsy drug ethosuximide. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[12]  M. Kamal,et al.  Nanotechnology-based approaches in anticancer research , 2012, International journal of nanomedicine.

[13]  B. Ahmed,et al.  Plausible antioxidant biomechanics and anticonvulsant pharmacological activity of brain-targeted β-carotene nanoparticles , 2012, International journal of nanomedicine.

[14]  Ashok Kumar,et al.  Formulation and evaluation of chitosan solid lipid nanoparticles of carbamazepine , 2012, Lipids in Health and Disease.

[15]  P. Diwan,et al.  Development of Olanzapine Nano-Emulsion for Enhanced Brain Delivery , 2012 .

[16]  M. Priyadarshini,et al.  Targeting Parkinson's - tyrosine hydroxylase and oxidative stress as points of interventions. , 2012, CNS & neurological disorders drug targets.

[17]  X. Wu,et al.  Nanotechnological advances for the delivery of CNS therapeutics. , 2012, Advanced drug delivery reviews.

[18]  Norman R. Saunders,et al.  Barrier Mechanisms in the Developing Brain , 2012, Front. Pharmacol..

[19]  Feng-Yi Yang,et al.  Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound , 2012, International journal of nanomedicine.

[20]  G. Salzano,et al.  Nanotechnologies: a strategy to overcome blood-brain barrier. , 2012, Current drug metabolism.

[21]  A. Azadi,et al.  Valproate‐Loaded hydrogel nanoparticles: Preparation and characterization , 2011 .

[22]  Y. Kumar,et al.  Influence of carvedilol on anticonvulsant effect of gabapentin. , 2011, Acta neurologica Belgica.

[23]  Z. Suntres,et al.  Liposomal Antioxidants for Protection against Oxidant-Induced Damage , 2011, Journal of toxicology.

[24]  C. Kumar,et al.  Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. , 2011, Advanced drug delivery reviews.

[25]  N. Pouratian,et al.  Impact of temozolomide chemotherapy on seizure frequency in patients with low-grade gliomas. , 2011, Journal of neurosurgery.

[26]  Kit S Lam,et al.  The effect of surface charge on in vivo biodistribution of PEG-oligocholic acid based micellar nanoparticles. , 2011, Biomaterials.

[27]  X. Su,et al.  Magnetic Nanoparticles in Brain Disease Diagnosis and Targeting Drug Delivery , 2011 .

[28]  S. Prijic,et al.  Magnetic nanoparticles as targeted delivery systems in oncology , 2011, Radiology and oncology.

[29]  Michael C Veronesi,et al.  Attenuation of kindled seizures by intranasal delivery of neuropeptide-loaded nanoparticles , 2009, Neurotherapeutics.

[30]  W. Mark Saltzman,et al.  Nanotechnology for delivery of drugs to the brain for epilepsy , 2009, Neurotherapeutics.

[31]  F. Ahmad,et al.  Antiepileptic intranasal Amiloride loaded mucoadhesive nanoemulsion: development and safety assessment. , 2011, Journal of biomedical nanotechnology.

[32]  É. R. Kinjo,et al.  Reactive oxygen species generated by NADPH oxidase are involved in neurodegeneration in the pilocarpine model of temporal lobe epilepsy , 2010, Neuroscience Letters.

[33]  Sohail Akhter,et al.  Insights into the novel three 'D's of epilepsy treatment: drugs, delivery systems and devices. , 2010, Drug discovery today.

[34]  V. Adam,et al.  Magnetic nanoparticles and targeted drug delivering. , 2010, Pharmacological research.

[35]  Sandipan Pati,et al.  Pharmacoresistant epilepsy: From pathogenesis to current and emerging therapies , 2010, Cleveland Clinic Journal of Medicine.

[36]  K. Nakken,et al.  [Benzodiazepines in the treatment of epilepsy]. , 2010, Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke.

[37]  H. Weiner,et al.  Role of the innate immune system in the pathogenesis of multiple sclerosis , 2010, Journal of Neuroimmunology.

[38]  G. Giammona,et al.  Brain-targeted solid lipid nanoparticles containing riluzole: preparation, characterization and biodistribution. , 2010, Nanomedicine.

[39]  Vasilis Ntziachristos,et al.  Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging , 2010, Particle and Fibre Toxicology.

[40]  Michael C Veronesi,et al.  Thyrotropin-releasing hormone d,l polylactide nanoparticles (TRH-NPs) protect against glutamate toxicity in vitro and kindling development in vivo , 2009, Brain Research.

[41]  San-Yuan Chen,et al.  A flexible drug delivery chip for the magnetically-controlled release of anti-epileptic drugs. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

[42]  M. Gatne,et al.  Nanoemulsion based Intranasal Delivery of Antimigraine Drugs for Nose to Brain Targeting , 2009, Indian Journal of Pharmaceutical Sciences.

[43]  Dong-sheng Wang,et al.  Preparation and drug releasing property of magnetic chitosan-5-fluorouracil nano-particles , 2009 .

[44]  A. Sigal,et al.  Pegylated nanoliposomes remote-loaded with the antioxidant tempamine ameliorate experimental autoimmune encephalomyelitis , 2009, Journal of Neuroimmunology.

[45]  H. Teixeira,et al.  Pharmacokinetic study of a carbamazepine nanoemulsion in beagle dogs. , 2009, International journal of pharmaceutics.

[46]  V. Pillay,et al.  Nanotechnological applications for the treatment of neurodegenerative disorders , 2009, Progress in neurobiology.

[47]  A. Mahmoud,et al.  Nanoemulsion as a Potential Ophthalmic Delivery System for Dorzolamide Hydrochloride , 2009, AAPS PharmSciTech.

[48]  A. Misra,et al.  Formulation and Characterization of Nanoemulsion-Based Drug Delivery System of Risperidone , 2009, Drug development and industrial pharmacy.

[49]  V. Torchilin,et al.  Tumor-Targeted Nanomedicines: Enhanced Antitumor Efficacy In vivo of Doxorubicin-Loaded, Long-Circulating Liposomes Modified with Cancer-Specific Monoclonal Antibody , 2009, Clinical Cancer Research.

[50]  G. Abdelbary,et al.  Diazepam-Loaded Solid Lipid Nanoparticles: Design and Characterization , 2009, AAPS PharmSciTech.

[51]  F. Ahmad,et al.  CNS drug delivery systems: novel approaches. , 2009, Recent patents on drug delivery & formulation.

[52]  M. Rizwan,et al.  Nanoemulsion Components Screening and Selection: a Technical Note , 2009, AAPS PharmSciTech.

[53]  Rex Moats,et al.  Functionalized magnetonanoparticles for MRI diagnosis and localization in epilepsy , 2008, Epilepsia.

[54]  A. Babbar,et al.  Intranasal nanoemulsion based brain targeting drug delivery system of risperidone. , 2008, International journal of pharmaceutics.

[55]  Norman R. Saunders,et al.  Barriers in the brain: a renaissance? , 2008, Trends in Neurosciences.

[56]  F. Ahmad,et al.  Development and Characterization of Liposome‐Based Formulation of Amiloride Hydrochloride , 2008 .

[57]  S. Baboota,et al.  Nanoemulsions as vehicles for transdermal delivery of aceclofenac , 2007, AAPS PharmSciTech.

[58]  M. Bally,et al.  Liposomal drug delivery: recent patents and emerging opportunities. , 2007, Recent patents on drug delivery & formulation.

[59]  H. Teixeira,et al.  Carbamazepine parenteral nanoemulsions prepared by spontaneous emulsification process. , 2007, International journal of pharmaceutics.

[60]  G. Yener,et al.  Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives , 2007, International journal of nanomedicine.

[61]  M. Ricci,et al.  Solid lipid nanoparticles for targeted brain drug delivery. , 2007, Advanced drug delivery reviews.

[62]  B. Youan,et al.  Formulation of spray-dried phenytoin loaded poly(epsilon-caprolactone) microcarrier intended for brain delivery to treat epilepsy. , 2007, Journal of pharmaceutical sciences.

[63]  D. Vohora,et al.  Comparative efficacy of liposome-entrapped amiloride and free amiloride in animal models of seizures and serum potassium in mice , 2007, European Neuropsychopharmacology.

[64]  D. Gopinath,et al.  1-O-alkylglycerol stabilized carbamazepine intravenous o/w nanoemulsions for drug targeting in mice , 2007, Journal of drug targeting.

[65]  K. Neoh,et al.  Synthesis and in vitro anti-cancer evaluation of tamoxifen-loaded magnetite/PLLA composite nanoparticles. , 2006, Biomaterials.

[66]  M. Nei,et al.  Temozolomide Treatment of Refractory Epilepsy in a Patient with an Oligodendroglioma , 2006, Epilepsia.

[67]  Charles Nicholson,et al.  In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[68]  R. Sharma,et al.  Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on brain targeting. , 2006, Journal of pharmaceutical sciences.

[69]  Ram B. Gupta,et al.  Formation of phenytoin nanoparticles using rapid expansion of supercritical solution with solid cosolvent (RESS-SC) process. , 2006, International journal of pharmaceutics.

[70]  E. Hansson,et al.  Astrocyte–endothelial interactions at the blood–brain barrier , 2006, Nature Reviews Neuroscience.

[71]  A. R. Kulkarni,et al.  Targeted nanoparticles for drug delivery through the blood-brain barrier for Alzheimer's disease. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[72]  C. Müller-Goymann,et al.  Drug release and permeation studies of nanosuspensions based on solidified reverse micellar solutions (SRMS). , 2005, International journal of pharmaceutics.

[73]  V. Venkateswarlu,et al.  Pharmacokinetics, tissue distribution and bioavailability of clozapine solid lipid nanoparticles after intravenous and intraduodenal administration. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[74]  Wolfgang Löscher,et al.  Drug resistance in brain diseases and the role of drug efflux transporters , 2005, Nature Reviews Neuroscience.

[75]  P. Couvreur,et al.  Colloidal carriers and blood-brain barrier (BBB) translocation: a way to deliver drugs to the brain? , 2005, International journal of pharmaceutics.

[76]  A. Göpferich,et al.  Polyethylenimine-based non-viral gene delivery systems. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[77]  R. Pandey,et al.  Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis. , 2005, Tuberculosis.

[78]  T. Davis,et al.  The Blood-Brain Barrier/Neurovascular Unit in Health and Disease , 2005, Pharmacological Reviews.

[79]  M. Schaller,et al.  RU 58841-myristate--prodrug development for topical treatment of acne and androgenetic alopecia. , 2005, Die Pharmazie.

[80]  Paul R. Lockman,et al.  Nanoparticle Surface Charges Alter Blood–Brain Barrier Integrity and Permeability , 2004, Journal of drug targeting.

[81]  R. Müller,et al.  Solid lipid nanoparticles for parenteral drug delivery. , 2004, Advanced drug delivery reviews.

[82]  Younghoon Kim,et al.  Self-assembled polymeric nanoparticles of poly(ethylene glycol) grafted pullulan acetate as a novel drug carrier , 2004, Archives of pharmacal research.

[83]  A. Sękowski,et al.  Riluzole enhances the anti-seizure action of conventional antiepileptic drugs against pentetrazole-induced convulsions in mice. , 2004, Polish journal of pharmacology.

[84]  J Szebeni,et al.  Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. , 2003, Progress in lipid research.

[85]  Y. Jeong,et al.  Polymeric nanoparticle composed of fatty acids and poly(ethylene glycol) as a drug carrier. , 2003, International journal of pharmaceutics.

[86]  G. Holmes,et al.  Effectiveness of Muscimol‐containing Microparticles against Pilocarpine‐induced Focal Seizures , 2002, Epilepsia.

[87]  N. Abbott,et al.  Astrocyte–endothelial interactions and blood–brain barrier permeability * , 2002 .

[88]  M. Whittington,et al.  A comparison of the efficacy of carbamazepine and the novel anti‐epileptic drug levetiracetam in the tetanus toxin model of focal complex partial epilepsy , 2002, British journal of pharmacology.

[89]  S. H. Kim,et al.  Evaluation of polymeric nanoparticles composed of cholic acid and methoxy poly(ethylene glycol). , 2001, International journal of pharmaceutics.

[90]  M. Sznitowska,et al.  Bioavailability of diazepam from aqueous-organic solution, submicron emulsion and solid lipid nanoparticles after rectal administration in rabbits. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[91]  S. Benbadis,et al.  Advances in the treatment of epilepsy. , 2001, American family physician.

[92]  K. Mäder,et al.  Solid lipid nanoparticles: production, characterization and applications. , 2001, Advanced drug delivery reviews.

[93]  U. Bickel,et al.  Delivery of peptides and proteins through the blood-brain barrier. , 1993, Advanced drug delivery reviews.

[94]  G. Barger,et al.  Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte-macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes. , 2000, Neurosurgical focus.

[95]  R Langer,et al.  In vitro and in vivo degradation of porous poly(DL-lactic-co-glycolic acid) foams. , 2000, Biomaterials.

[96]  J. Nah,et al.  Clonazepam release from core-shell type nanoparticles of poly(ε-caprolactone)/poly(ethylene glycol)/poly(ε-caprolactone) triblock copolymers , 2000 .

[97]  K. Dziegielewska,et al.  BARRIER MECHANISMS IN THE BRAIN, II. IMMATURE BRAIN , 1999, Clinical and experimental pharmacology & physiology.

[98]  K. Dziegielewska,et al.  BARRIER MECHANISMS IN THE BRAIN, I. ADULT BRAIN , 1999, Clinical and experimental pharmacology & physiology.

[99]  K. Kelly Gabapentin. Antiepileptic mechanism of action. , 1998, Neuropsychobiology.

[100]  J. Nah,et al.  Clonazepam release from poly(DL-lactide-co-glycolide) nanoparticles prepared by dialysis method , 1998, Archives of pharmacal research.

[101]  M. Ueda,et al.  Optimization of the preparation of loperamide-loaded poly (L-lactide) nanoparticles by high pressure emulsification-solvent evaporation. , 1997, Journal of microencapsulation.

[102]  J. Huwyler,et al.  Brain drug delivery of small molecules using immunoliposomes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[103]  G. Cavallaro,et al.  Preparation and characterization of polyethyl-2-cyanoacrylate nanocapsules containing antiepileptic drugs. , 1996, Biomaterials.

[104]  Katsuaki Suzuki,et al.  Liposome-entrapped phenytoin locally suppresses amygdaloid epileptogenic focus created by db-cAMP/EDTA in rats , 1995, Brain Research.

[105]  N. Mori,et al.  Anticonvulsant Effect of DN‐1417, a Derivative of Thyrotropin‐Releasing Hormone, and Liposome‐Entrapped DN‐1417, on Amygdaloid‐Kindled Rats , 1992, Epilepsia.

[106]  H. Kumashiro,et al.  Anticonvulsant effect of liposome-entrapped superoxide dismutase in amygdaloid-kindled rats , 1992, Brain Research.

[107]  A. Gabizon,et al.  Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[108]  T. Zeuthen Secondary active transport of water across ventricular cell membrane of choroid plexus epithelium of Necturus maculosus. , 1991, The Journal of physiology.

[109]  T M Allen,et al.  Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. , 1991, Biochimica et biophysica acta.

[110]  C. Loeb,et al.  Liposome‐Entrapped γ‐Aminobutyric Acid Inhibits Isoniazid‐Induced Epileptogenic Activity in Rats , 1986 .

[111]  R. Spector Thymidine transport and metabolism in choroid plexus: effect of diazepam and thiopental. , 1985, The Journal of pharmacology and experimental therapeutics.

[112]  C. Loeb,et al.  Liposome‐entrapped GABA modifies behavioral and electrographic changes of penicillin‐induced epileptic activity , 1982, Neurology.

[113]  A. Richens,et al.  Bioavailability of diazepam after intravenous, oral and rectal administration in adult epileptic patients. , 1982, British journal of clinical pharmacology.

[114]  T. Browne,et al.  Benzodiazepines in the Treatment of Epilepsy A Review , 1973, Epilepsia.

[115]  T. Reese,et al.  JUNCTIONS BETWEEN INTIMATELY APPOSED CELL MEMBRANES IN THE VERTEBRATE BRAIN , 1969, The Journal of cell biology.