Gelatin nanoparticles enhance the neuroprotective effects of intranasally administered osteopontin in rat ischemic stroke model

Abstract

As a leading cause of death and adult disability, ischemic stroke requires the development of non-invasive, long-acting treatments. Osteopontin (OPN) is an endogenous protein shown to have neuroprotective effects in the post-ischemic brain of rats when administered through the non-invasive, intranasal pathway. Previously, gelatin microspheres (GMSs) have been shown to enhance the neuroprotective effects of OPN when used as a carrier during instrastriatal administration, but GMSs are generally too large to enter the brain parenchyma following intranasal administration. Here, gelatin nanoparticles (GNPs) were investigated as a carrier for intranasal delivery of an OPN peptide for the treatment of ischemic stroke. We not only successfully fabricated GNPs with a uniform shape, but also demonstrated the ability of these GNPs to pass into the brain parenchyma following intranasal administration. Critically, the use of GNPs as a carrier allowed for a 71.57 % reduction in mean infarct volume and extended the therapeutic window of intranasally administered OPN peptide to at least 6 h post-middle cerebral artery occlusion (MCAO). Our findings support the development of GNPs as a promising drug delivery platform for the intranasal treatment of ischemic stroke and, potentially, other neurologic disorders.

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Acknowledgments

This work was financially supported by Research Grants funded by the National Research Foundation of Korea Global Research Network (NRF-220-2011-E00027), Trionix Research Laboratory, Inc., and by a Whitaker International Summer Grant from the Institute of International Education. This work was carried out in part in the Frederick Seitz Materials Research Laboratory Central Facilities, University of Illinois.

All institutional and national guidelines for the care and use of laboratory animals were followed.

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All authors declare that they have no conflict of interest.

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Correspondence to Ja-Kyeong Lee or Hyungsoo Choi.

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Joachim, E., Kim, I., Jin, Y. et al. Gelatin nanoparticles enhance the neuroprotective effects of intranasally administered osteopontin in rat ischemic stroke model. Drug Deliv. and Transl. Res. 4, 395–399 (2014). https://doi.org/10.1007/s13346-014-0208-9

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Keywords

  • Osteopontin
  • Neuroprotection
  • Ischemic stroke
  • Gelatin nanoparticles
  • Intranasal delivery