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Int. J. Mol. Sci. 2017, 18(1), 28; doi:10.3390/ijms18010028

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

1
Center for Nanomedicine & Drug Delivery, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA
2
Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 28 September 2016 / Revised: 2 December 2016 / Accepted: 14 December 2016 / Published: 24 December 2016
(This article belongs to the Collection Radiation Toxicity in Cells)
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Abstract

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. View Full-Text
Keywords: γ-tocotrienol; GT3; nanoemulsion; dry emulsion; radioprotection; lyophilization γ-tocotrienol; GT3; nanoemulsion; dry emulsion; radioprotection; lyophilization
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MDPI and ACS Style

Ledet, G.A.; Biswas, S.; Kumar, V.P.; Graves, R.A.; Mitchner, D.M.; Parker, T.M.; Bostanian, L.A.; Ghosh, S.P.; Mandal, T.K. Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection. Int. J. Mol. Sci. 2017, 18, 28.

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