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Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies

An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising...

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Autores principales: Nair, Sreeja C., Vinayan, Kollencheri Puthenveettil, Mangalathillam, Sabitha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540129/
https://www.ncbi.nlm.nih.gov/pubmed/34683933
http://dx.doi.org/10.3390/pharmaceutics13101640
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author Nair, Sreeja C.
Vinayan, Kollencheri Puthenveettil
Mangalathillam, Sabitha
author_facet Nair, Sreeja C.
Vinayan, Kollencheri Puthenveettil
Mangalathillam, Sabitha
author_sort Nair, Sreeja C.
collection PubMed
description An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50–100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures.
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spelling pubmed-85401292021-10-24 Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies Nair, Sreeja C. Vinayan, Kollencheri Puthenveettil Mangalathillam, Sabitha Pharmaceutics Article An acute epileptic seizure is a seizure emergency fatal condition that requires immediate medical attention. IV phenytoin sodium remains the second line therapeutic agent for the immediate treatment of status epilepticus. Phenytoin sodium formulated as nanolipid carriers (NLCs) seems to be promising as an intranasal delivery system for controlling acute seizures. Three different nanosized phenytoin sodium loaded NLCs (<50 nm, 50–100 nm and >100 nm) were prepared by melt emulsification and was further characterised. In vitro drug release studies showed immediate drug release from phenytoin sodium loaded NLCs of <50 nm size, which is highly essential for acute seizure control. The ex vivo permeation study indicated greater permeation from <50 nm sized NLC through the olfactory epithelium compared to thecontrol drug solution. Invivo pharmacokinetic studies revealed higher drug concentration in CSF/brain within 5 min upon intranasal administration of <50 nm sized phenytoin sodium NLCs than the control drug solution and marketed IV phenytoin sodium, indicating direct and rapid nose to brain drug transport through the olfactory epithelium. The study has shown that formulation strategies can enhance olfactory uptake, and phenytoin sodium NLCs of desired particle sizes (<50 nm) offer promising potential for nose to brain direct delivery of phenytoin sodium in treating acute epileptic seizures. MDPI 2021-10-08 /pmc/articles/PMC8540129/ /pubmed/34683933 http://dx.doi.org/10.3390/pharmaceutics13101640 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nair, Sreeja C.
Vinayan, Kollencheri Puthenveettil
Mangalathillam, Sabitha
Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies
title Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies
title_full Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies
title_fullStr Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies
title_full_unstemmed Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies
title_short Nose to Brain Delivery of Phenytoin Sodium Loaded Nano Lipid Carriers: Formulation, Drug Release, Permeation and In Vivo Pharmacokinetic Studies
title_sort nose to brain delivery of phenytoin sodium loaded nano lipid carriers: formulation, drug release, permeation and in vivo pharmacokinetic studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540129/
https://www.ncbi.nlm.nih.gov/pubmed/34683933
http://dx.doi.org/10.3390/pharmaceutics13101640
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