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Biodistribution of the cationic host defense peptide LL-37 using SPECT/CT.

Tullio V F Esposito1, Cristina Rodríguez-Rodríguez2, Colin Blackadar1

  • 1Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V
|July 7, 2024
PubMed
Summary

This study tracked the distribution of human cathelicidin LL-37 in mice after administration. The peptide showed distinct biodistribution patterns depending on whether it was given intravenously or subcutaneously, offering insights into its therapeutic potential.

Keywords:
BiodistributionCathelicidinHost defense peptideLL-37SPECT/CT

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Immunology

Background:

  • Human cathelicidin LL-37 (a cationic host defense peptide) has known roles in immunity and wound healing.
  • Its therapeutic potential is under investigation, but the biodistribution of externally administered LL-37 is not well understood.

Purpose of the Study:

  • To assess the biodistribution of exogenously administered LL-37 in healthy mice.
  • To understand the pharmacokinetic behavior of LL-37 following different administration routes.

Main Methods:

  • A gallium-67 labeled variant of LL-37 was used as a radiotracer.
  • Nuclear imaging techniques were employed over a 48-hour period in mice.
  • Control scans with free gallium-67 were also performed.

Main Results:

  • Intravenous administration led to rapid blood clearance, primarily by the liver, with temporary lung distribution.
  • Subcutaneous administration showed a two-phase systemic absorption, with predominant renal clearance.
  • Both administration routes resulted in uptake in immune cell-rich tissues like lymph nodes and spleen.

Conclusions:

  • This study provides crucial preclinical data on the biodistribution of exogenously administered LL-37.
  • The findings aid in understanding the behavior of LL-37 and related cationic host defense peptides for therapeutic development.