PEGylated Polyester Nanoparticles Trigger Adverse Events in a Large Animal Model of Trauma and in Nal¨ve Animals: Understanding Cytokine and Cellular Correlations with These Events

Nuzhat Maisha, Chhaya Kulkarni, Narendra Pandala, Rose Zilberberg, Leasha Schaub, Leslie Neidert, Jacob Glaser, Jeremy Cannon, Vandana Janeja, Erin B. Lavik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Intravenously infusible nanoparticles to control bleeding have shown promise in rodents, but translation into preclinical models has been challenging as many of these nanoparticle approaches have resulted in infusion responses and adverse outcomes in large animal trauma models. We developed a hemostatic nanoparticle technology that was screened to avoid one component of the infusion response: complement activation. We administered these hemostatic nanoparticles, control nanoparticles, or saline volume controls in a porcine polytrauma model. While the hemostatic nanoparticles promoted clotting as marked by a decrease in prothrombin time and both the hemostatic nanoparticles and controls did not active complement, in a subset of the animals, hard thrombi were found in uninjured tissues in both the hemostatic and control nanoparticle groups. Using data science methods that allow one to work across heterogeneous data sets, we found that the presence of these thrombi correlated with changes in IL-6, INF-alpha, lymphocytes, and neutrophils. While these findings might suggest that this formulation would not be a safe one for translation for trauma, they provide guidance for developing screening tools to make nanoparticle formulations in the complex milieux of trauma as well as for therapeutic interventions more broadly. This is important as we look to translate intravenously administered nanoparticle formulations for therapies, particularly considering the vascular changes seen in a subset of patients following COVID-19. We need to understand adverse events like thrombi more completely and screen for these events early to make nanomaterials as safe and effective as possible.

Original languageEnglish
Pages (from-to)10566-10580
Number of pages15
JournalACS Nano
Volume16
Issue number7
DOIs
StatePublished - 26 Jul 2022
Externally publishedYes

Keywords

  • IL-6
  • TNF-alpha
  • hemorrhage
  • hemostasis
  • inflammation
  • lymphocytes
  • neutrophils

Fingerprint

Dive into the research topics of 'PEGylated Polyester Nanoparticles Trigger Adverse Events in a Large Animal Model of Trauma and in Nal¨ve Animals: Understanding Cytokine and Cellular Correlations with These Events'. Together they form a unique fingerprint.

Cite this