In vivo (Athens, Greece) · 2018
Evaluation of Different Formulations and Routes for the Delivery of the Ionizing Radiation Mitigator GS-Nitroxide (JP4-039).
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Epperly Michael W, Wipf Peter, Fisher Renee, Franicola Darcy, Beumer Jan, Li Song, Brand Rhonda M, Falo Louis D, Erdos Geza, Greenberger Joel S
Аннотация
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.
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.
Предметные рубрики MeSH
Administration, IntravenousAdministration, OralAnimalsApoptosisDNA DamageDNA RepairDrug Administration RoutesDrug CompoundingDrug StabilityFemaleInjections, IntramuscularMiceMice, KnockoutMitochondriaMolecular StructureNitrogen OxidesRadiation Injuries, ExperimentalRadiation, IonizingRadiation-Protective AgentsReproducibility of ResultsSurvival RateWhole-Body Irradiation