← Back to Search
Brain Delivery Of Valproic Acid Via Intranasal Administration Of Nanostructured Lipid Carriers: In Vivo Pharmacodynamic Studies Using Rat Electroshock Model
S. Eskandari, J. Varshosaz, M. Minaiyan, M. Tabbakhian
Published 2011 · Medicine
Download PDFAnalyze on Scholarcy
The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the brain for a prolonged period. The objective of this study was delivery of valproic acid (VPA) to the brain by intranasal route. For this purpose, nanostructured lipid carriers (NLCs) were prepared by solvent diffusion method followed by ultrasonication and characterized for size, zeta potential, drug-loading percentage, and release. Six groups of rats each containing six animals received drug-loaded NLCs intraperitoneally (IP) or intranasally. Brain responses were then examined by using maximal electroshock (MES). The hind limb tonic extension:flexion inhibition ratio was measured at 15-, 30-, 60-, 90-, and 120-minute intervals. The drug concentration was also measured in plasma and brain at the most protective point using gas chromatography method. The particle size of NLCs was 154 ± 16 nm with drug-loading percentage of 47% ± 0.8% and drug release of 75% ± 1.9% after 21 days. In vivo results showed that there was a significant difference between protective effects of NLCs of VPA and control group 15, 30, 60, and 90 minutes after treatment via intranasal route (P < 0.05). Similar protective effect was observed in rats treated with NLCs of VPA in intranasal route and positive control in IP route (P > 0.05). Results of drug determination in brain and plasma showed that brain:plasma concentration ratio was much higher after intranasal administration of NLCs of VPA than the positive control group (IP route). In conclusion, intranasal administration of NLCs of VPA provided a better protection against MES seizure.
This paper references
Formulation and optimization of solid lipid nanoparticles of buspirone HCl for enhancement of its oral bioavailability
J. Varshosaz (2010)
Solid lipid nanoparticles for targeted brain drug delivery.
P. Blasi (2007)
Intranasal mucoadhesive microemulsions of zolmitriptan: Preliminary studies on brain-targeting
Tushar K Vyas (2005)
LEIDEN/AMSTERDAM CENTER FOR DRUG RESEARCH
Production and optimization of valproic acid nanostructured lipid carriers by the Taguchi design
J. Varshosaz (2010)
In vivo evidence for brain-to-blood efflux transport of valproic acid across the blood-brain barrier.
A. Kakee (2002)
Animal models of epilepsy for the development of antiepileptogenic and disease-modifying drugs. A comparison of the pharmacology of kindling and post-status epilepticus models of temporal lobe epilepsy
W. Löscher (2002)
Is nose‐to‐brain transport of drugs in man a reality?
L. Illum (2004)
Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation on the targeting efficiency to the brain.
Q. Zhang (2004)
Nasal drug delivery : A direct approach to the cerebrospinal fluid?
M. Berg (2005)
Direct Nose-to-Brain Transfer of Morphine After Nasal Administration to Rats
U. Westin (2006)
Preliminary brain-targeting studies on intranasal mucoadhesive microemulsions of sumatriptan.
Tushar K Vyas (2006)
Brain delivery of VPA via intranasal administration of nanostructured lipid carriers
Potential of solid lipid nanoparticles in brain targeting.
I. P. Kaur (2008)
Plasma and cerebrospinal fluid pharmacokinetics of valproic acid after oral administration in non-human primates
S. Stapleton (2007)
Nanosized cationic hydrogels for drug delivery: preparation, properties and interactions with cells.
S. Vinogradov (2002)
Intranasal nanoemulsion based brain targeting drug delivery system of risperidone.
M. Kumar (2008)
Epilepsy : a comprehensive textbook
J. Engel (2008)
Electrically Induced Convulsions
F. Golla (1940)
Blood–Brain Barrier Transport of Valproic Acid
E. Cornford (1985)
Increase of the duration of the anticonvulsive activity of a novel NMDA receptor antagonist using poly(butylcyanoacrylate) nanoparticles as a parenteral controlled release system.
A. Friese (2000)
HPLC determination of valproic acid in human serum.
P. Kishore (2003)
Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on brain targeting.
Tushar K Vyas (2006)
Valproate: a reappraisal of its pharmacodynamic properties and mechanisms of action
W. Löscher (1999)
Potential of nanoparticulate drug delivery systems by intranasal administration.
J. Ali (2010)
Nasal Drug Delivery System-Factors Affecting and Applications
K. Jadhav (2007)
Colloidal carriers and blood-brain barrier (BBB) translocation: a way to deliver drugs to the brain?
E. García-García (2005)
The nose and paranasal sinuses physiology and anatomy.
N. Jones (2001)
Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles.
V. Venkateswarlu (2004)
Nanoparticles for direct nose-to-brain delivery of drugs.
Alpesh Mistry (2009)
Experimental Models of Epilepsy. A Manual for the Laboratory Worker
J. Pincus (1974)
Valproic acid uptake by bovine brain microvessel endothelial cells: role of active efflux transport
J. Gibbs (2004)
Plasma and cerebrospinal fluid pharmacokinetics of ABT-888 after oral administration in non-human primates
J. Muscal (2009)
Effect of physicochemical properties on intranasal nanoparticle transit into murine olfactory epithelium
Alpesh Mistry (2009)
Valproic Acid Is Not a Substrate for P-glycoprotein or Multidrug Resistance Proteins 1 and 2 in a Number of in Vitro and in Vivo Transport Assays
S. Baltes (2007)
Pharmacokinetics, tissue distribution and bioavailability of clozapine solid lipid nanoparticles after intravenous and intraduodenal administration.
K. Manjunath (2005)
Intranasal delivery: physicochemical and therapeutic aspects.
H. Costantino (2007)
Current status and future directions in the pharmacotherapy of epilepsy.
W. Löscher (2002)
Methods to reduce background interferences in electron-capture gas chromatographic analysis of valproic acid and its unsaturated metabolites after derivatization with pentafluorobenzyl bromide.
R. Dills (1997)
Carbamazepine uptake into rat brain following intra‐olfactory transport
N. Barakat (2006)
Transport of drugs from the nasal cavity to the central nervous system.
L. Illum (2000)
Determination of valproic acid in human serum and pharmaceutical preparations by headspace liquid-phase microextraction gas chromatography-flame ionization detection without prior derivatization.
Parvin Shahdousti (2007)
Experimental Models of Epilepsy--a Manual for the Laboratory Worker
D. Purpura (1972)
Probenecid-inhibitable efflux transport of valproic acid in the brain parenchymal cells of rabbits: a microdialysis study
J. L. Scism (2000)
A simple, rapid gas-liquid chromatographic procedure for the determination of valproic acid in serum.
A. Wohler (1997)
This paper is referenced by
Nanomedicine in Central Nervous System (CNS) Disorders: A Present and Future Prospective.
Shringika Soni (2016)
A review of intranasal formulations for the treatment of seizure emergencies.
M. Kapoor (2016)
Direct Brain Targeted Nanostructured Lipid Carriers for Sustained Release of Schizophrenic Drug: Formulation, Characterization and Pharmacokinetic Studies
Praveen Sivadasu (2019)
Translational gap in ongoing clinical trials for glioma
Alecia Florence Guishard (2018)
Pharmacoresistant epilepsy and nanotechnology.
Argelia Rosillo-de la Torre (2014)
Fabrication and Characterization of Pluronic F 68 and Phospholipon 90 g Embedded Nanoformulation for Sertraline Delivery : An Optimized Factorial Design Approach and In Vivo Study
Kushwaha Krishna (2019)
Advances in Neurotherapeutic Delivery Technologies
V. Pillay (2015)
Nasal-to-CNS drug delivery: where are we now and where are we heading? An industrial perspective.
Margaret S. Landis (2012)
Intranasal delivery of asenapine loaded nanostructured lipid carriers: formulation, characterization, pharmacokinetic and behavioural assessment
S. Singh (2016)
Nasal-nanotechnology: revolution for efficient therapeutics delivery
A. Kumar (2016)
The beneficial effects of l-cysteine on brain antioxidants of rats affected by sodium valproate
RZ Hamza (2017)
Management of epileptic disorders using nanotechnology-based strategies for nose-to-brain drug delivery.
Mihika Shringarpure (2020)
Phenytoin carried by silica core iron oxide nanoparticles reduces the expression of pharmacoresistant seizures in rats.
Argelia Rosillo-de la Torre (2015)
Scope of Nasal Drug Delivery : Current Challenges
Nancy Jaiswal (2017)
Nose-to-brain delivery of lipid-based nanosystems for epileptic seizures and anxiety crisis
Cl�udia Pina Costa (2019)
Evaluation of sodium valproate loaded nanoparticles in acute and chronic pentylenetetrazole induced seizure models
Meenakshi Meenu (2019)
Nasal Drug Delivery-A Pre Hospital Therapy in Status Epilepsy-Review
Follicular delivery of spironolactone via nanostructured lipid carriers for management of alopecia
R. Shamma (2014)
Ursolic acid rich Ocimum sanctum L leaf extract loaded nanostructured lipid carriers ameliorate adjuvant induced arthritis in rats by inhibition of COX-1, COX-2, TNF-α and IL-1: Pharmacological and docking studies
A. Ahmad (2018)
Intranasal delivery of chitosan-siRNA nanoparticle formulation to the brain.
M. Malhotra (2014)
An overview of the neuroprotective potential of rosmarinic acid and its association with nanotechnology-based delivery systems: A novel approach to treating neurodegenerative disorders
F. N. S. Fachel (2019)
Nose to brain transport pathways an overview: potential of nanostructured lipid carriers in nose to brain targeting
Kousalya Selvaraj (2018)
Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug transport across the placenta and fetal drug exposure
F. Staud (2012)
Zian Wang (2019)
Formulation and optimization of nanostructured lipid carriers to enhance oral bioavailability of telmisartan using Box–Behnken design
Chhitij Thapa (2018)
Recent strategies and advances in the fabrication of nano lipid carriers and their application towards brain targeting.
Mukta Agrawal (2020)
Pharmacoresistance in Epilepsy
L. Rocha (2013)
Application of RPMI 2650 as a cell model to evaluate solid formulations for intranasal delivery of drugs.
V. S. Gonçalves (2016)
Nose to Brain Delivery of Rivastigmine by In Situ Gelling Cationic Nanostructured Lipid Carriers: Enhanced Brain Distribution and Pharmacodynamics.
Preeti Wavikar (2017)
Preparation, characterization, and in vivo pharmacokinetics of nanostructured lipid carriers loaded with oleanolic acid and gentiopicrin
K. Zhang (2013)
Intranasal administration: a prospective drug delivery route to the brain
A. Privalova (2012)
Nose-to-brain delivery: exploring newer domains for glioblastoma multiforme management
Prashant G. Upadhaya (2020)See more