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In Vivo. 2018 Sep-Oct;32(5):1009-1023. doi: 10.21873/invivo.11341.

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

Author information

1
Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A.
2
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, U.S.A.
3
Department of Pharmaceutical Science, University of Pittsburgh, Pittsburgh, PA, U.S.A.
4
Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, U.S.A.
5
Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, U.S.A. greenbergerjs@upmc.edu.

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-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.

KEYWORDS:

Ionizing irradiation; JP4-039; radiation mitigation

PMID:
30150422
PMCID:
PMC6199586
DOI:
10.21873/invivo.11341
[Indexed for MEDLINE]
Free PMC Article

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