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Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection

The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrie...

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Autores principales: Ledet, Grace A., Biswas, Shukla, Kumar, Vidya P., Graves, Richard A., Mitchner, Demaurian M., Parker, Taylor M., Bostanian, Levon A., Ghosh, Sanchita P., Mandal, Tarun K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297663/
https://www.ncbi.nlm.nih.gov/pubmed/28029115
http://dx.doi.org/10.3390/ijms18010028
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author Ledet, Grace A.
Biswas, Shukla
Kumar, Vidya P.
Graves, Richard A.
Mitchner, Demaurian M.
Parker, Taylor M.
Bostanian, Levon A.
Ghosh, Sanchita P.
Mandal, Tarun K.
author_facet Ledet, Grace A.
Biswas, Shukla
Kumar, Vidya P.
Graves, Richard A.
Mitchner, Demaurian M.
Parker, Taylor M.
Bostanian, Levon A.
Ghosh, Sanchita P.
Mandal, Tarun K.
author_sort Ledet, Grace A.
collection PubMed
description The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrienol was incorporated into a nanoemulsion and lyophilized with lactose. Ultra performance liquid chromatography–mass spectroscopy (UPLC–MS) was used to monitor the chemical stability of GT3 over time, the particle size and ζ potential, and scanning electron microscopy (SEM) were used to study the physical stability of the nanoemulsion. Radioprotective and toxicity studies were performed in mice. The liquid formulation exhibited GT3 degradation at all storage temperatures. Lyophilization, in the presence of lactose, significantly reduced GT3 degradation. Both the liquid and lyophilized nanoemulsions had stable particle size and ζ potential when stored at 4 °C. Toxicity studies of the nanoemulsion resulted in no observable toxicity in mice at an oral dose of 600 mg/kg GT3. The nano-formulated GT3 (300 mg/kg) demonstrated enhanced survival efficacy compared to GT3 alone (200 and 400 mg/kg) in CD2F1 mice exposed to total body gamma radiation. The optimal long-term storage of formulated GT3 is as a powder at −20 °C to preserve drug and formulation integrity. Formulation of GT3 as a nanoemulsion for oral delivery as a prophylactic radioprotectant shows promise and warrants further investigation.
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spelling pubmed-52976632017-02-10 Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection Ledet, Grace A. Biswas, Shukla Kumar, Vidya P. Graves, Richard A. Mitchner, Demaurian M. Parker, Taylor M. Bostanian, Levon A. Ghosh, Sanchita P. Mandal, Tarun K. Int J Mol Sci Article The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrienol was incorporated into a nanoemulsion and lyophilized with lactose. Ultra performance liquid chromatography–mass spectroscopy (UPLC–MS) was used to monitor the chemical stability of GT3 over time, the particle size and ζ potential, and scanning electron microscopy (SEM) were used to study the physical stability of the nanoemulsion. Radioprotective and toxicity studies were performed in mice. The liquid formulation exhibited GT3 degradation at all storage temperatures. Lyophilization, in the presence of lactose, significantly reduced GT3 degradation. Both the liquid and lyophilized nanoemulsions had stable particle size and ζ potential when stored at 4 °C. Toxicity studies of the nanoemulsion resulted in no observable toxicity in mice at an oral dose of 600 mg/kg GT3. The nano-formulated GT3 (300 mg/kg) demonstrated enhanced survival efficacy compared to GT3 alone (200 and 400 mg/kg) in CD2F1 mice exposed to total body gamma radiation. The optimal long-term storage of formulated GT3 is as a powder at −20 °C to preserve drug and formulation integrity. Formulation of GT3 as a nanoemulsion for oral delivery as a prophylactic radioprotectant shows promise and warrants further investigation. MDPI 2016-12-24 /pmc/articles/PMC5297663/ /pubmed/28029115 http://dx.doi.org/10.3390/ijms18010028 Text en © 2016 by the authors; 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ledet, Grace A.
Biswas, Shukla
Kumar, Vidya P.
Graves, Richard A.
Mitchner, Demaurian M.
Parker, Taylor M.
Bostanian, Levon A.
Ghosh, Sanchita P.
Mandal, Tarun K.
Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection
title Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection
title_full Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection
title_fullStr Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection
title_full_unstemmed Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection
title_short Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection
title_sort development of orally administered γ-tocotrienol (gt3) nanoemulsion for radioprotection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297663/
https://www.ncbi.nlm.nih.gov/pubmed/28029115
http://dx.doi.org/10.3390/ijms18010028
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