Sex-dependent improvement in traumatic brain injury outcomes after liposomal delivery of dexamethasone in mice

Gherardo Baudo, Hannah Flinn, Morgan Holcomb, Anjana Tiwari, Sirena Soriano, Francesca Taraballi, Biana Godin, Assaf Zinger, Sonia Villapol

Research output: Contribution to journalArticlepeer-review

Abstract

Traumatic brain injury (TBI) can have long-lasting physical, emotional, and cognitive consequences due to the neurodegeneration caused by its robust inflammatory response. Despite advances in rehabilitation care, effective neuroprotective treatments for TBI patients are lacking. Furthermore, current drug delivery methods for TBI treatment are inefficient in targeting inflamed brain areas. To address this issue, we have developed a liposomal nanocarrier (Lipo) encapsulating dexamethasone (Dex), an agonist for the glucocorticoid receptor utilized to alleviate inflammation and swelling in various conditions. In vitro studies show that Lipo-Dex were well tolerated in human and murine neural cells. Lipo-Dex showed significant suppression of inflammatory cytokines, IL-6 and TNF-α, release after induction of neural inflammation with lipopolysaccharide. Further, the Lipo-Dex were administered to young adult male and female C57BL/6 mice immediately after controlled cortical impact injury (a TBI model). Our findings demonstrate that Lipo-Dex can selectively target the injured brain, thereby reducing lesion volume, cell death, astrogliosis, the release of pro-inflammatory cytokines, and microglial activation compared to Lipo-treated mice in a sex-dependent manner, showing a major impact only in male mice. This highlights the importance of considering sex as a crucial variable in developing and evaluating new nano-therapies for brain injury. These results suggest that Lipo-Dex administration may effectively treat acute TBI.

Original languageEnglish
JournalBioengineering and Translational Medicine
DOIs
StateAccepted/In press - 2024

Keywords

  • brain injury
  • cytokines
  • drug delivery
  • glucocorticoid
  • inflammation
  • sex differences

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biomedical Engineering
  • Pharmaceutical Science

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