Background/aim: The mitochondrial targeted GS-nitroxide, JP4-039, is an effective total body irradiation (TBI) mitigator when delivered intravenously (IV) up to 72 h after exposure. Effective systemic and localized administration to oral cavity/oropharynx and esophagus has been demonstrated. The objective of the study was to establish alternatives to IV administration suitable for JP4-039 delivery to mass casualties.
Materials And Methods: JP4-039 was administered to C57BL/6 mice by topically applied carboxy-methyl-cellulose microneedle arrays (MNAs) or by intramuscular (IM) injection. Three different formulations that have passed Food and Drug Administration review, namely Captisol, 2-hydroxypropyl-β-cyclodextrin (cyclodextrin), and Miglyol-812-N, were used for drug delivery. Intraoral (IO) administration with each formulation was also evaluated.
Results: All tested formulations and MNAs successfully delivered JP4-039. However, IM delivery of the Miglyol-812-N displayed very efficient and highly reproducible radiation mitigation.
Conclusion: Effective IM delivery of JP4-039 in animal models after TBI or partial-body irradiation suggested the use of the Miglyol-812-N formulation in both medical indications and radiation countermeasures.
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| http://dx.doi.org/10.21873/invivo.11341 | DOI Listing |
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Mitigation of Fetal Radiation Injury from Mid-Gestation Total-body Irradiation by Maternal Administration of Mitochondrial-Targeted GS-Nitroxide JP4-039.
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Department of Radiation Oncology, School of Medicine, UPMC Hillman Cancer Center, Pittsburgh, PA 15232.
Victims of a radiation terrorist event will include pregnant women and unborn fetuses. Mitochondrial dysfunction and oxidative stress are key pathogenic factors of fetal radiation injury. The goal of this preclinical study is to investigate the efficacy of mitigating fetal radiation injury by maternal administration of the mitochondrial-targeted gramicidin S (GS)-nitroxide radiation mitigator JP4-039.
View Article and Find Full Text PDFUnlabelled: Victims of a radiation terrorist event will include pregnant women and unborn fetuses. Mitochondrial dysfunction and oxidative stress are key pathogenic factors of fetal irradiation injury. The goal of this preclinical study is to investigate the efficacy of mitigating fetal irradiation injury by maternal administration of the mitochondrial-targeted gramicidin S (GS)- nitroxide radiation mitigator, JP4-039.
View Article and Find Full Text PDFFanconi Anemia Mouse Genotype-specific Mitigation of Total Body Irradiation by GS-Nitroxide JP4-039.
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Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
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Department of Radiation Oncology, Beaumont Health, Royal Oak, MI, U.S.A.
Background/aim: We tested JP4-039, a GS-nitroxide radiation damage mitigator in proton therapy of Fanconi anemia (FA) mice.
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Evaluation of Different Formulations and Routes for the Delivery of the Ionizing Radiation Mitigator GS-Nitroxide (JP4-039).
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Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
Background/aim: The mitochondrial targeted GS-nitroxide, JP4-039, is an effective total body irradiation (TBI) mitigator when delivered intravenously (IV) up to 72 h after exposure. Effective systemic and localized administration to oral cavity/oropharynx and esophagus has been demonstrated. The objective of the study was to establish alternatives to IV administration suitable for JP4-039 delivery to mass casualties.
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