Nanotechnology for delivery of drugs to the brain for epilepsy

SummaryEpilepsy results from aberrant electrical activity that can affect either a focal area or the entire brain. In treating epilepsy with drugs, the aim is to decrease seizure frequency and severity while minimizing toxicity to the brain and other tissues. Antiepileptic drugs (AEDs) are usually administered by oral and intravenous routes, but these drug treatments are not always effective. Drug access to the brain is severely limited by a number of biological factors, particularly the blood—brain barrier, which impedes the ability of AEDs to enter and remain in the brain. To improve the efficacy of AEDs, new drug delivery strategies are being developed; these methods fall into the three main categories: drug modification, blood—brain barrier modification, and direct drug delivery. Recently, all three methods have been improved through the use of drug-loaded nanoparticles.

[1]  M. Joshi,et al.  Parasitic diseases: Liposomes and polymeric nanoparticles versus lipid nanoparticles. , 2007, Advanced drug delivery reviews.

[2]  S. Rapoport Modulation of blood-brain barrier permeability. , 1996, Journal of drug targeting.

[3]  M. Mayberg,et al.  Overexpression of Multiple Drug Resistance Genes in Endothelial Cells from Patients with Refractory Epilepsy , 2001, Epilepsia.

[4]  R. North,et al.  Implantable pumps for drug delivery to the brain , 1995, Journal of Neuro-Oncology.

[5]  R. Müller Colloidal Carriers for Controlled Drug Delivery and Targeting: Modification, Characterization, and In Vivo Distribution , 1991 .

[6]  M. Zignani,et al.  Current status of pH-sensitive liposomes in drug delivery. , 2000, Progress in lipid research.

[7]  C. Cho,et al.  Polyethylene glycol (PEG) modified 99mTc-HMPAO-liposome for improving blood circulation and biodistribution: the effect of the extent of PEGylation. , 2005, Cancer biotherapy & radiopharmaceuticals.

[8]  P F Morrison,et al.  Focal delivery during direct infusion to brain: role of flow rate, catheter diameter, and tissue mechanics. , 1999, American journal of physiology. Regulatory, integrative and comparative physiology.

[9]  J. Huwyler,et al.  Drug transport to brain with targeted liposomes , 2005 .

[10]  Peter Ramge,et al.  Apolipoprotein-mediated Transport of Nanoparticle-bound Drugs Across the Blood-Brain Barrier , 2002, Journal of drug targeting.

[11]  W. Pardridge,et al.  Drug Delivery to the Brain , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[12]  P. Parisi,et al.  Calcium‐channel Blocker Verapamil Administration in Prolonged and Refractory Status Epilepticus , 2005, Epilepsia.

[13]  W. Löscher,et al.  Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein , 2007, Neuropharmacology.

[14]  Tycho Heimbach,et al.  Prodrugs: design and clinical applications , 2008, Nature Reviews Drug Discovery.

[15]  Nicolas de Tribolet,et al.  Outwitting the Blood-Brain Barrier for Therapeutic Purposes: Osmotic Opening and Other Means , 1998 .

[16]  J. Pardeike,et al.  Nanostructured lipid carriers (NLC) in cosmetic dermal products. , 2007, Advanced drug delivery reviews.

[17]  W. Olbricht,et al.  Fabrication and characterization of microfluidic probes for convection enhanced drug delivery. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[18]  M. Kubek,et al.  Prolonged seizure suppression by a single implantable polymeric-TRH microdisk preparation , 1998, Brain Research.

[19]  A. Vortmeyer,et al.  Local distribution and toxicity of prolonged hippocampal infusion of muscimol. , 2005, Journal of neurosurgery.

[20]  Masoud Alasvand Zarasvand,et al.  Effect of transient hippocampal inhibition on amygdaloid kindled seizures and amygdaloid kindling rate , 2002, Brain Research.

[21]  Wolfgang Löscher,et al.  The multidrug transporter hypothesis of drug resistance in epilepsy: Proof-of-principle in a rat model of temporal lobe epilepsy , 2006, Neurobiology of Disease.

[22]  Joseph D. Andrade,et al.  Protein—surface interactions in the presence of polyethylene oxide: II. Effect of protein size , 1991 .

[23]  W. Löscher,et al.  Multidrug Resistance Protein MRP2 Contributes to Blood-Brain Barrier Function and Restricts Antiepileptic Drug Activity , 2003, Journal of Pharmacology and Experimental Therapeutics.

[24]  Betty M Tyler,et al.  The intracerebral administration of phenytoin using controlled-release polymers reduces experimental seizures in rats , 2002, Epilepsy Research.

[25]  Jean-Christophe Olivier,et al.  Drug transport to brain with targeted nanoparticles , 2011, NeuroRX.

[26]  E. Aronica,et al.  Expression of Multidrug Transporters MRP1, MRP2, and BCRP Shortly after Status Epilepticus, during the Latent Period, and in Chronic Epileptic Rats , 2005, Epilepsia.

[27]  E. Neuwelt,et al.  Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means. , 1998, Neurosurgery.

[28]  Raghu Raghavan,et al.  Convection-enhanced delivery of therapeutics for brain disease, and its optimization. , 2006, Neurosurgical focus.

[29]  N. Barbaro,et al.  MDR1 Gene Expression in Brain of Patients with Medically Intractable Epilepsy , 1995, Epilepsia.

[30]  R. Langer,et al.  Transport rates of proteins in porous materials with known microgeometry. , 1989, Biophysical journal.

[31]  E. Oldfield,et al.  Surface properties, more than size, limiting convective distribution of virus-sized particles and viruses in the central nervous system. , 2005, Journal of neurosurgery.

[32]  E. Perucca,et al.  Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V) , 2001, Epilepsy Research.

[33]  R. Fisher,et al.  Focally injected adenosine prevents seizures in the rat , 2004, Experimental Neurology.

[34]  L. Knapp,et al.  Clinical Experience With Fosphenytoin in Adults: Pharmacokinetics, Safety, and Efficacy , 1998, Journal of child neurology.

[35]  P. Pávek,et al.  Lack of Interactions between Breast Cancer Resistance Protein (BCRP/ABCG2) and Selected Antiepileptic Agents , 2006, Epilepsia.

[36]  L. Brannon-Peppas,et al.  Optimization of Preparation Techniques for Poly(Lactic Acid-Co-Glycolic Acid) Nanoparticles , 2000 .

[37]  W. Mark Saltzman,et al.  New Methods for Direct Delivery of Chemotherapy for Treating Brain Tumors , 2006, The Yale journal of biology and medicine.

[38]  J. C. Baayen,et al.  Expression and Cellular Distribution of Multidrug Resistance–related Proteins in the Hippocampus of Patients with Mesial Temporal Lobe Epilepsy , 2004, Epilepsia.

[39]  M. Rogawski,et al.  Prolonged Attenuation of Amygdala-Kindled Seizure Measures in Rats by Convection-Enhanced Delivery of the N-Type Calcium Channel Antagonists ω-Conotoxin GVIA and ω-Conotoxin MVIIA , 2007, Journal of Pharmacology and Experimental Therapeutics.

[40]  P F Morrison,et al.  Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time. , 1999, Journal of neurosurgery.

[41]  R. Gonzalez,et al.  A nanostructured titania bioceramic implantable device capable of drug delivery to the temporal lobe of the brain , 2007 .

[42]  J. Drewe,et al.  Endocytosis and Transcytosis of an Immunoliposome-Based Brain Drug Delivery System , 2000, Journal of drug targeting.

[43]  M. Yıldırım,et al.  Anticonvulsant effects of focal and intracerebroventricular adenosine on penicillin-induced epileptiform activity in rats , 2007, Brain Research.

[44]  S. Krähenbühl,et al.  Targeting of daunomycin using biotinylated immunoliposomes: Pharmacokinetics, tissue distribution and in vitro pharmacological effects , 2005, Journal of drug targeting.

[45]  Imad Najm,et al.  Seizure‐Promoting Effect of Blood–Brain Barrier Disruption , 2007, Epilepsia.

[46]  R. Barrett,et al.  XP13512 [(±)-1-([(α-Isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane Acetic Acid], A Novel Gabapentin Prodrug: I. Design, Synthesis, Enzymatic Conversion to Gabapentin, and Transport by Intestinal Solute Transporters , 2004, Journal of Pharmacology and Experimental Therapeutics.

[47]  R. Barrett,et al.  XP13512 [(±)-1-([(α-Isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane Acetic Acid], A Novel Gabapentin Prodrug: II. Improved Oral Bioavailability, Dose Proportionality, and Colonic Absorption Compared with Gabapentin in Rats and Monkeys , 2004, Journal of Pharmacology and Experimental Therapeutics.

[48]  Patrick Couvreur,et al.  Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26. , 2005, Bioconjugate chemistry.

[49]  Kevin J. Kelly,et al.  Gabapentin , 1998, Neuropsychobiology.

[50]  M. E. Hernández,et al.  Effect of intracerebroventricular continuous infusion of valproic acid versus single i.p. and i.c.v. injections in the amygdala kindling epilepsy model , 2006, Epilepsy Research.

[51]  D D Allen,et al.  Nanoparticle Technology for Drug Delivery Across the Blood-Brain Barrier , 2002, Drug development and industrial pharmacy.

[52]  Jean-Pierre Benoit,et al.  Active targeting of brain tumors using nanocarriers. , 2007, Biomaterials.

[53]  K. Avgoustakis,et al.  Effect of dose on the biodistribution and pharmacokinetics of PLGA and PLGA-mPEG nanoparticles. , 2001, International journal of pharmaceutics.

[54]  M. Radeke,et al.  Distribution of Intracerebral Ventricularly Administered Neurotrophins in Rat Brain and Its Correlation with Trk Receptor Expression , 1994, Experimental Neurology.

[55]  Amarnath Sharma,et al.  Liposomes in drug delivery: Progress and limitations , 1997 .

[56]  J. Moore,et al.  Use of Verapamil as a Potential P-Glycoprotein Inhibitor in a Patient with Refractory Epilepsy , 2004, The Annals of pharmacotherapy.

[57]  H. García-Rivello,et al.  Neuronal and Glial Expression of the Multidrug Resistance Gene Product in an Experimental Epilepsy Model , 2004, Cellular and Molecular Neurobiology.

[58]  C. Nicholson,et al.  Cell cavities increase tortuosity in brain extracellular space. , 2005, Journal of theoretical biology.

[59]  M. V. Catania,et al.  Expression of multidrug resistance type 1 gene (MDR1) P-glycoprotein in intractable epilepsy with different aetiologies: a double-labelling and electron microscopy study , 2006, Neurological Sciences.

[60]  W. Mark Saltzman,et al.  Chemotherapeutic Drugs Released from Polymers: Distribution of 1,3-bis(2-chloroethyl)-l-nitrosourea in the Rat Brain , 1996, Pharmaceutical Research.

[61]  G. Barratt,et al.  Therapeutic applications of colloidal drug carriers. , 2000, Pharmaceutical science & technology today.

[62]  Y. Cai,et al.  Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[63]  G. Khuller,et al.  Liposomes and PLG microparticles as sustained release antitubercular drug carriers--an in vitro-in vivo study. , 2001, International journal of antimicrobial agents.

[64]  E. Aronica,et al.  Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. , 2007, Brain : a journal of neurology.

[65]  L. Fenart,et al.  Evaluation of effect of charge and lipid coating on ability of 60-nm nanoparticles to cross an in vitro model of the blood-brain barrier. , 1999, The Journal of pharmacology and experimental therapeutics.

[66]  M. Bilsky,et al.  Ommaya reservoirs for the treatment of leptomeningeal metastases. , 2000, Neurosurgery.

[67]  K. Makino,et al.  Incorporation of water-soluble drugs in PLGA microspheres. , 2007, Colloids and surfaces. B, Biointerfaces.

[68]  W. Löscher,et al.  Blood-brain barrier active efflux transporters: ATP-binding cassette gene family , 2005 .

[69]  Yechezkel Barenholz,et al.  Pharmacokinetics of Pegylated Liposomal Doxorubicin , 2003, Clinical pharmacokinetics.

[70]  P. Couvreur,et al.  Nanotechnology: Intelligent Design to Treat Complex Disease , 2006, Pharmaceutical Research.

[71]  T. Minko,et al.  Receptor targeted polymers, dendrimers, liposomes: which nanocarrier is the most efficient for tumor-specific treatment and imaging? , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[72]  W. Hennink,et al.  Temperature-sensitive poly(N-(2-hydroxypropyl)methacrylamide mono/dilactate)-coated liposomes for triggered contents release. , 2007, Bioconjugate chemistry.

[73]  M. Gomori,et al.  In vivo assessment of the window of barrier opening after osmotic blood-brain barrier disruption in humans. , 2000, Journal of neurosurgery.

[74]  Nicholas A Peppas,et al.  Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. , 2006, International journal of pharmaceutics.

[75]  W. Pardridge Blood-brain barrier drug targeting: the future of brain drug development. , 2003, Molecular interventions.

[76]  M. Brightman,et al.  Permeable Endothelium and the Interstitial Space of Brain , 2000, Cellular and Molecular Neurobiology.

[77]  R. Aird A study of intrathecal, cerebrospinal fluid-to-brain exchange , 1984, Experimental Neurology.

[78]  J. Parker Overcoming Multidrug Resistance in Cancer: An Update on the Clinical Strategy of Inhibiting P-Glycoprotein , 2003 .

[79]  Norberto Garcia-Cairasco,et al.  EEG wavelet analyses of the striatum–substantia nigra pars reticulata–superior colliculus circuitry: Audiogenic seizures and anticonvulsant drug administration in Wistar audiogenic rats (War strain) , 2006, Epilepsy Research.

[80]  Eric Pridgen,et al.  Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles , 2008, Molecular pharmaceutics.

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

[82]  F. Szoka,et al.  Distribution in brain of liposomes after convection enhanced delivery; modulation by particle charge, particle diameter, and presence of steric coating , 2005, Brain Research.

[83]  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.

[84]  V. Levin,et al.  High-Grade Gliomas: Diagnosis and Treatment , 2007 .

[85]  M. Thom,et al.  Multidrug-resistance protein 1 in focal cortical dysplasia , 2001, The Lancet.

[86]  A. Billiau,et al.  Tissue distribution of human interferons after exogenous administration in rabbits, monkeys, and mice , 2005, Archives of Virology.

[87]  W. Mark Saltzman,et al.  Building drug delivery into tissue engineering design , 2002, Nature Reviews Drug Discovery.

[88]  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.

[89]  Joseph D. Andrade,et al.  Protein—surface interactions in the presence of polyethylene oxide , 1991 .

[90]  Y. Eto,et al.  Liposome targeting to mouse brain: mannose as a recognition marker. , 1988, Biochemical and biophysical research communications.

[91]  Robert S Fisher,et al.  Potential New Methods for Antiepileptic Drug Delivery , 2002, CNS drugs.

[92]  D. Kraemer,et al.  Association of Total Dose Intensity of Chemotherapy in Primary Central Nervous System Lymphoma (Human Non-Acquired Immunodeficiency Syndrome) and Survival , 2001, Neurosurgery.

[93]  Robert S. Fisher,et al.  Intraventricular administration of gabapentin in the rat increases flurothyl seizure threshold , 2007, Neuroscience Letters.

[94]  L. Martinian,et al.  Vascular colocalization of P‐glycoprotein, multidrug‐resistance associated protein 1, breast cancer resistance protein and major vault protein in human epileptogenic pathologies , 2006, Neuropathology and applied neurobiology.

[95]  Y. Tabata,et al.  Intraocular sustained drug delivery using implantable polymeric devices. , 2005, Advanced drug delivery reviews.

[96]  P. Couvreur,et al.  Stealth® PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting , 1999 .

[97]  W. Saltzman,et al.  Pharmacokinetics of interstitial delivery of carmustine, 4-hydroperoxycyclophosphamide, and paclitaxel from a biodegradable polymer implant in the monkey brain. , 1998, Cancer research.

[98]  J. Fechner,et al.  Pharmacokinetics and pharmacodynamics of GPI 15715 or fospropofol (Aquavan injection) - a water-soluble propofol prodrug. , 2008, Handbook of experimental pharmacology.

[99]  P. Lockman,et al.  The blood-brain barrier choline transporter as a brain drug delivery vector. , 2003, Life sciences.

[100]  René H. Levy,et al.  Progress report on new antiepileptic drugs: A summary of the Eigth Eilat Conference (EILAT VIII) , 2007, Epilepsy Research.

[101]  D. Trombetta,et al.  Design and Characterization of Liposomes Containing Long-Chain N-AcylPEs for Brain Delivery: Penetration of Liposomes Incorporating GM1 into the Rat Brain , 2002, Pharmaceutical Research.

[102]  M R Gaab,et al.  Expression of multidrug transporters in dysembryoplastic neuroepithelial tumors causing intractable epilepsy. , 2004, Clinical neuropathology.

[103]  E. Aronica,et al.  Expression and cellular distribution of multidrug transporter proteins in two major causes of medically intractable epilepsy: focal cortical dysplasia and glioneuronal tumors , 2003, Neuroscience.

[104]  D. Covell,et al.  Kinetic model for disposition of 6-mercaptopurine in monkey plasma and cerebrospinal fluid. , 1985, The American journal of physiology.

[105]  M. Haluska,et al.  Osmotic blood-brain barrier modification for the treatment of malignant brain tumors. , 2004, Clinical journal of oncology nursing.

[106]  Alan Connelly,et al.  EEG‐fMRI in Children with Pharmacoresistant Focal Epilepsy , 2007, Epilepsia.

[107]  J. Huwyler,et al.  Receptor mediated delivery of daunomycin using immunoliposomes: pharmacokinetics and tissue distribution in the rat. , 1997, The Journal of pharmacology and experimental therapeutics.

[108]  R. Gonzalez,et al.  The determination of dielectric constants of mixtures used in the treatment of epilepsy and the encapsulation of phenytoin in a titania matrix , 2007 .

[109]  R. A. Jain,et al.  The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. , 2000, Biomaterials.

[110]  Bernd Büchner,et al.  Carbon nanotube based biomedical agents for heating, temperature sensoring and drug delivery , 2008, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[111]  Mansoor M. Amiji,et al.  Poly(ethylene glycol)-modified Nanocarriers for Tumor-targeted and Intracellular Delivery , 2007, Pharmaceutical Research.

[112]  R. Cavalli,et al.  Intravenous Administration to Rabbits of Non-stealth and Stealth Doxorubicin-loaded Solid Lipid Nanoparticles at Increasing Concentrations of Stealth Agent: Pharmacokinetics and Distribution of Doxorubicin in Brain and Other Tissues , 2002, Journal of drug targeting.

[113]  W. Pardridge Transport of small molecules through the blood-brain barrier: biology and methodology. , 1995, Advanced drug delivery reviews.

[114]  M. Krzyżanowski,et al.  New generation of valproic acid. , 2004, Polish journal of pharmacology.

[115]  G. Luijtelaar,et al.  Absence seizures are reduced by the enhancement of GABA-ergic inhibition in the hippocampus in WAG/Rij rats , 2007, Neuroscience Letters.

[116]  A. Hart,et al.  The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study. , 2004, European journal of cancer.

[117]  O. Lindvall,et al.  Seizure suppression in kindling epilepsy by intracerebral implants of GABA- but not by noradrenaline-releasing polymer matrices , 2004, Experimental Brain Research.

[118]  P. Couvreur,et al.  Tissue distribution of doxorubicin associated with polyisohexylcyanoacrylate nanoparticles , 2008, Cancer Chemotherapy and Pharmacology.

[119]  J. Kreuter,et al.  Increase of the duration of the anticonvulsive activity of a novel NMDA receptor antagonist using poly(butylcyanoacrylate) nanoparticles as a parenteral controlled release system. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.