Epilepsy Disease and Nose-to-Brain Delivery of Polymeric Nanoparticles: An Overview

Epilepsy is the fourth most common global neurological problem, which can be considered a spectrum disorder because of its various causes, seizure types, its ability to vary in severity and the impact from person to person, as well as its range of co-existing conditions. The approaches to drug therapy of epilepsy are directed at the control of symptoms by chronic administration of antiepileptic drugs (AEDs). These AEDs are administered orally or intravenously but alternative routes of administration are needed to overcome some important limits. Intranasal (IN) administration represents an attractive route because it is possible to reach the brain bypassing the blood brain barrier while the drug avoids first-pass metabolism. It is possible to obtain an increase in patient compliance for the easy and non-invasive route of administration. This route, however, has some drawbacks such as mucociliary clearance and the small volume that can be administered, in fact, only drugs that are efficacious at low doses can be considered. The drug also needs excellent aqueous solubility or must be able to be formulated using solubilizing agents. The use of nanomedicine formulations able to encapsulate active molecules represents a good strategy to overcome several limitations of this route and of conventional drugs. The aim of this review is to discuss the innovative application of nanomedicine for epilepsy treatment using nose-to-brain delivery with particular attention focused on polymeric nanoparticles to load drugs.

[1]  Chandrakantsing V. Pardeshi,et al.  Nanotechnology-mediated nose to brain drug delivery for Parkinson's disease: a mini review , 2015, Journal of drug targeting.

[2]  B. Kumar,et al.  Antiepileptic drugs in development pipeline: A recent update , 2016, eNeurologicalSci.

[3]  Michael C Veronesi,et al.  Intranasal Delivery of a Thyrotropin‐Releasing Hormone Analog Attenuates Seizures in the Amygdala‐Kindled Rat , 2007, Epilepsia.

[4]  S. Yamashita,et al.  Direct Drug Transport from the Rat Nasal Cavity to the Cerebrospinal Fluid: the Relation to the Molecular Weight of Drugs , 1995, The Journal of pharmacy and pharmacology.

[5]  P. Mehta,et al.  Intranasal insulin improves cognition and modulates β-amyloid in early AD , 2008, Neurology.

[6]  William H Frey II Noninvasive intranasal stem cells bypass the blood-brain barrier to target the brain to treat Parkinson's disease, stroke, MS, brain tumors, cerebral ischemia, Alzheimer's and other CNS disorders , 2015 .

[7]  Björn Bauer,et al.  Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers , 2017, Front. Neurol..

[8]  R. Kukreti,et al.  Effect of Oxidative Stress on ABC Transporters: Contribution to Epilepsy Pharmacoresistance , 2017, Molecules.

[9]  S. Nair,et al.  Intra Nasal In situ Gelling System of Lamotrigine Using Ion Activated Mucoadhesive Polymer , 2017, The open medicinal chemistry journal.

[10]  Per Gisle Djupesland,et al.  Nasal drug delivery devices: characteristics and performance in a clinical perspective—a review , 2012, Drug Delivery and Translational Research.

[11]  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.

[12]  M. R. Lauro,et al.  Revisiting the role of sucrose in PLGA-PEG nanocarrier for potential intranasal delivery , 2018, Pharmaceutical development and technology.

[13]  D. Zochodne,et al.  Motor End Plate Innervation Loss in Diabetes and the Role of Insulin , 2011, Journal of neuropathology and experimental neurology.

[14]  V. Ivaturi,et al.  Bioavailability of Intranasal vs. Rectal Diazepam , 2013, Epilepsy Research.

[15]  L. Casettari,et al.  Chitosan in nasal delivery systems for therapeutic drugs. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[16]  Genetic Epilepsy Syndromes Without Structural Brain Abnormalities: Clinical Features and Experimental Models , 2014, Neurotherapeutics.

[17]  D. Vohora,et al.  Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: in vitro characterization and in vivo efficacy in epilepsy , 2015, Expert opinion on drug delivery.

[18]  Xinfeng Liu Clinical trials of intranasal delivery for treating neurological disorders – a critical review , 2011, Expert opinion on drug delivery.

[19]  Lisbeth Illum,et al.  Nanoparticles for direct nose-to-brain delivery of drugs. , 2009, International journal of pharmaceutics.

[20]  Robert S Fisher,et al.  The New Classification of Seizures by the International League Against Epilepsy 2017 , 2017, Current Neurology and Neuroscience Reports.

[21]  Alan B. Watts,et al.  Formulation and device design to increase nose to brain drug delivery , 2016 .

[22]  S. Barhate,et al.  ADVANTAGEOUS NASAL DRUG DELIVERY SYSTEM: A REVIEW , 2011 .

[23]  Huile Gao,et al.  Progress and perspectives on targeting nanoparticles for brain drug delivery , 2016, Acta pharmaceutica Sinica. B.

[24]  F. Erdő,et al.  Evaluation of intranasal delivery route of drug administration for brain targeting , 2018, Brain Research Bulletin.

[25]  W. Hsu,et al.  Mechanism of intranasal drug delivery directly to the brain , 2018, Life sciences.

[26]  L. Casettari,et al.  A Tailored Thermosensitive PLGA-PEG-PLGA/Emulsomes Composite for Enhanced Oxcarbazepine Brain Delivery via the Nasal Route , 2018, Pharmaceutics.

[27]  Ronald A Siegel,et al.  A review of intranasal formulations for the treatment of seizure emergencies. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[28]  K. Schindowski,et al.  Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa , 2018, Pharmaceutics.

[29]  S. Stolnik,et al.  Nose-to-Brain Delivery: Investigation of the Transport of Nanoparticles with Different Surface Characteristics and Sizes in Excised Porcine Olfactory Epithelium. , 2015, Molecular pharmaceutics.

[30]  Ranjitkumar N Patil,et al.  Oxcarbazepine: Drug of the Future in the Treatment of Trigeminal Neuralgia , 2011 .

[31]  R. D'Hooge,et al.  Pathophysiology of epilepsy. , 2000, Acta neurologica Belgica.

[32]  C. Tuleu,et al.  Rectal route in the 21st Century to treat children. , 2014, Advanced drug delivery reviews.

[33]  A. M. Dyer,et al.  Nasal Delivery of Insulin Using Novel Chitosan Based Formulations: A Comparative Study in Two Animal Models Between Simple Chitosan Formulations and Chitosan Nanoparticles , 2002, Pharmaceutical Research.

[34]  C. Biçer,et al.  Nasal and Buccal Treatment of Midazolam in Epileptic Seizures in Pediatrics , 2012, Clinical medicine insights. Pediatrics.

[35]  A. Falcão,et al.  Intranasal administration of carbamazepine to mice: a direct delivery pathway for brain targeting. , 2014, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[36]  Xinguo Jiang,et al.  Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[37]  Preeta Caroline,et al.  Sublingual Tablets and the Benefits of the Sublingual Route of Administration , 2017 .

[38]  P. Di Martino,et al.  Optimization of Curcumin Nanocrystals as Promising Strategy for Nose-to-Brain Delivery Application , 2020, Pharmaceutics.

[39]  Chandrakantsing V. Pardeshi,et al.  Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood–brain barrier: an excellent platform for brain targeting , 2013, Expert opinion on drug delivery.

[40]  T. Montine,et al.  Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment A Pilot Clinical Trial , 2011 .

[41]  R. Saneto,et al.  Current oral and non-oral routes of antiepileptic drug delivery. , 2012, Advanced drug delivery reviews.

[42]  Rashmin B. Patel,et al.  Microemulsion-based drug delivery system for transnasal delivery of Carbamazepine: preliminary brain-targeting study , 2014, Drug delivery.

[43]  G. Awad,et al.  Identifying lipidic emulsomes for improved oxcarbazepine brain targeting: In vitro and rat in vivo studies. , 2016, International journal of pharmaceutics.

[44]  C. Johannessen Landmark,et al.  Prevalence of Different Combinations of Antiepileptic Drugs and CNS Drugs in Elderly Home Care Service and Nursing Home Patients in Norway , 2016, Epilepsy research and treatment.

[45]  Dieter Schmidt,et al.  Modern antiepileptic drug development has failed to deliver: Ways out of the current dilemma , 2011, Epilepsia.

[46]  W. Frey,et al.  Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation , 2015, Neuroscience Letters.

[47]  G. Schellenberg,et al.  Effects of intranasal insulin on cognition in memory-impaired older adults: Modulation by APOE genotype , 2006, Neurobiology of Aging.

[48]  Edouard Hirsch,et al.  ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology , 2017, Epilepsia.

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

[50]  Morgan Le Guen,et al.  Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. , 2012, Pharmacology & therapeutics.

[51]  Rohit K. Sharma,et al.  Bioengineered PLGA-chitosan nanoparticles for brain targeted intranasal delivery of antiepileptic TRH analogues , 2018, Chemical Engineering Journal.

[52]  Adriana O. Santos,et al.  Nanosystems in nose‐to‐brain drug delivery: A review of non‐clinical brain targeting studies , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[53]  P. Srihari,et al.  NASAL DRUG DELIVERY: A POTENTIAL ROUTE FOR BRAIN TARGETTING , 2015 .

[54]  L. Illum Nasal drug delivery--possibilities, problems and solutions. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[55]  P. Djupesland,et al.  The nasal approach to delivering treatment for brain diseases: an anatomic, physiologic, and delivery technology overview. , 2014, Therapeutic delivery.

[56]  Ahmed Awad E. Ahmed,et al.  Carbamazepine uptake into rat brain following intra‐olfactory transport , 2006, The Journal of pharmacy and pharmacology.

[57]  E. Brittebo,et al.  Transfer of morphine along the olfactory pathway to the central nervous system after nasal administration to rodents. , 2005, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[58]  J. Kjems,et al.  Effect of physicochemical properties on intranasal nanoparticle transit into murine olfactory epithelium , 2009, Journal of drug targeting.

[59]  Francesco Brigo,et al.  Pharmacotherapy for Status Epilepticus , 2015, Drugs.

[60]  H. Potschka Modulating P‐glycoprotein regulation: Future perspectives for pharmacoresistant epilepsies? , 2010, Epilepsia.

[61]  C. Carbone,et al.  Innovative hybrid vs polymeric nanocapsules: The influence of the cationic lipid coating on the "4S". , 2016, Colloids and surfaces. B, Biointerfaces.

[62]  M. Goldenberg,et al.  Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment. , 2010, P & T : a peer-reviewed journal for formulary management.

[63]  Yuzhen Wang,et al.  Primary Studies on Construction and Evaluation of Ion-Sensitive in situ Gel Loaded with Paeonol-Solid Lipid Nanoparticles for Intranasal Drug Delivery , 2020, International journal of nanomedicine.

[64]  Rakesh K. Sharma,et al.  Formulation and Optimization of Polymeric Nanoparticles for Intranasal Delivery of Lorazepam Using Box-Behnken Design: In Vitro and In Vivo Evaluation , 2014, BioMed research international.

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

[66]  H. Cui,et al.  Alleviation of Oxidative Damage and Involvement of Nrf2-ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline , 2017, Oxidative medicine and cellular longevity.

[67]  L. Carmant,et al.  Seizures and epilepsy: an overview for neuroscientists. , 2015, Cold Spring Harbor perspectives in medicine.

[68]  A. Schatzlein,et al.  Strategies to deliver peptide drugs to the brain. , 2014, Molecular pharmaceutics.

[69]  M. Serapide,et al.  Nose to brain delivery in rats: Effect of surface charge of rhodamine B labeled nanocarriers on brain subregion localization. , 2017, Colloids and surfaces. B, Biointerfaces.

[70]  P. Pasinelli,et al.  Regulation of ABC efflux transporters at blood-brain barrier in health and neurological disorders , 2015, Brain Research.

[71]  M. Amaral,et al.  Nose-to-brain delivery of lipid-based nanosystems for epileptic seizures and anxiety crisis , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[72]  T. Glauser Oxcarbazepine in the Treatment of Epilepsy , 2001, Pharmacotherapy.

[73]  E. Magiorkinis,et al.  Highights in the History of Epilepsy: The Last 200 Years , 2014, Epilepsy research and treatment.

[74]  V. Karri,et al.  Nose to brain transport pathways an overview: potential of nanostructured lipid carriers in nose to brain targeting , 2017, Artificial cells, nanomedicine, and biotechnology.

[75]  Z. Zuo,et al.  Intranasal Delivery—Modification of Drug Metabolism and Brain Disposition , 2010, Pharmaceutical Research.

[76]  M. Alonso,et al.  Nose-to-brain peptide delivery - The potential of nanotechnology. , 2017, Bioorganic & medicinal chemistry.

[77]  P. Campolongo,et al.  Lipid nanoparticles for administration of poorly water soluble neuroactive drugs , 2017, Biomedical microdevices.

[78]  R. G. Thorne,et al.  Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration , 2004, Neuroscience.

[79]  D. Spencer Auras Are Frequent in Patients with Generalized Epilepsy , 2015, Epilepsy currents.

[80]  D. Stepensky,et al.  Quantitative analysis of drug delivery to the brain via nasal route. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[81]  L. Illum Transport of drugs from the nasal cavity to the central nervous system. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[82]  R. Goldman,et al.  Intranasal midazolam for seizure cessation in the community setting. , 2016, Canadian family physician Medecin de famille canadien.

[83]  M. C. Bonferoni,et al.  Nose-to-Brain Delivery , 2020, Pharmaceutics.

[84]  N. E. El Sayed,et al.  Superparamagnetic Iron Oxide-Loaded Lipid Nanocarriers Incorporated in Thermosensitive In Situ Gel for Magnetic Brain Targeting of Clonazepam. , 2018, Journal of pharmaceutical sciences.

[85]  M. Hashida,et al.  The transport of a drug to the cerebrospinal fluid directly from the nasal cavity: the relation to the lipophilicity of the drug. , 1991, Chemical & pharmaceutical bulletin.

[86]  L. Ferraro,et al.  Oxcarbazepine free or loaded PLGA nanoparticles as effective intranasal approach to control epileptic seizures in rodents , 2018, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[87]  D. Begley,et al.  Drug resistance in epilepsy: the role of the blood-brain barrier. , 2002, Novartis Foundation symposium.

[88]  Rakesh K. Sharma,et al.  Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles , 2015, AAPS PharmSciTech.

[89]  Mengrui Liu,et al.  Progress in brain targeting drug delivery system by nasal route , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[90]  Seyed M. Mirsattari,et al.  Epilepsy, Mental Health Disorder, or Both? , 2011, Epilepsy research and treatment.

[91]  G. Mustafa,et al.  Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: pharmacodynamic, pharmacokinetic and scintigraphy study in mice model. , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[92]  Harish Padh,et al.  Application of quality by design approach for intranasal delivery of rivastigmine loaded solid lipid nanoparticles: Effect on formulation and characterization parameters. , 2015, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[93]  Ritesh M Pabari,et al.  Comparative evaluation of the degree of pegylation of poly(lactic‐co‐glycolic acid) nanoparticles in enhancing central nervous system delivery of loperamide , 2013, The Journal of pharmacy and pharmacology.

[94]  L. Illum Nasal drug delivery - recent developments and future prospects. , 2012, Journal of controlled release : official journal of the Controlled Release Society.