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Evaluation of Different Formulations and Routes for the Delivery of the Ionizing Radiation Mitigator GS-Nitroxide (JP4-039).


ABSTRACT: 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-?-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.

SUBMITTER: Epperly MW 

PROVIDER: S-EPMC6199586 | biostudies-literature | 2018 Sep-Oct

REPOSITORIES: biostudies-literature

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Evaluation of Different Formulations and Routes for the Delivery of the Ionizing Radiation Mitigator GS-Nitroxide (JP4-039).

Epperly Michael W MW   Wipf Peter P   Fisher Renee R   Franicola Darcy D   Beumer Jan J   Li Song S   Brand Rhonda M RM   Falo Louis D LD   Erdos Geza G   Greenberger Joel S JS  

In vivo (Athens, Greece) 20180901 5


<h4>Background/aim</h4>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.<h4>Materials and methods</h4>JP4-039 was administered to C57BL/6 mice by  ...[more]

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