Biodistribution of Native and Nanoformulated Innate Defense Regulator Peptide 1002Click to copy article linkArticle link copied!
- Tullio V. F. Esposito*Tullio V. F. Esposito*Email: [email protected]Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, CanadaMore by Tullio V. F. Esposito
- Colin BlackadarColin BlackadarFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, CanadaMore by Colin Blackadar
- Lan WuLan WuFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, CanadaWuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, Shenyang 110016, ChinaMore by Lan Wu
- Cristina Rodríguez-RodríguezCristina Rodríguez-RodríguezFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, CanadaDepartment of Physics and Astronomy, Faculty of Science, University of British Columbia, Vancouver V6T 1Z4, British Columbia, CanadaMore by Cristina Rodríguez-Rodríguez
- Evan F. HaneyEvan F. HaneyCentre for Microbial Disease and Immunity Research, Department of Microbiology and Immunology, Faculty of Science, University of British Columbia, Vancouver V6T 1Z4, British Columbia, CanadaAsep Medical Holdings, 420 – 730 View Street, Victoria V8W 3Y7, British Columbia, CanadaMore by Evan F. Haney
- Daniel Pletzer*Daniel Pletzer*Email: [email protected]. Phone: +64 3 479 7478.Centre for Microbial Disease and Immunity Research, Department of Microbiology and Immunology, Faculty of Science, University of British Columbia, Vancouver V6T 1Z4, British Columbia, CanadaDepartment of Microbiology and Immunology, University of Otago, Dunedin 9054, New ZealandMore by Daniel Pletzer
- Katayoun SaatchiKatayoun SaatchiFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, CanadaMore by Katayoun Saatchi
- Robert E. W. HancockRobert E. W. HancockCentre for Microbial Disease and Immunity Research, Department of Microbiology and Immunology, Faculty of Science, University of British Columbia, Vancouver V6T 1Z4, British Columbia, CanadaMore by Robert E. W. Hancock
- Urs O. HäfeliUrs O. HäfeliFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, CanadaDepartment of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 1172, DenmarkMore by Urs O. Häfeli
Abstract
Innate defense regulator-1002 (IDR-1002) is a synthetic peptide with promising immunomodulatory and antibiofilm properties. An appreciable body of work exists around its mechanism of action at the cellular and molecular level, along with its efficacy across several infection and inflammation models. However, little is known about its absorption, distribution, and excretion in live organisms. Here, we performed a comprehensive biodistribution assessment with a gallium-67 radiolabeled derivative of IDR-1002 using nuclear tracing techniques. Various dose levels of the radiotracer (2–40 mg/kg) were administered into the blood, peritoneal cavity, and subcutaneous tissue, or instilled into the lungs. The peptide was well tolerated at all subcutaneous and intraperitoneal doses, although higher levels were associated with delayed absorption kinetics and precipitation of the peptide within the tissues. Low intratracheal doses were rapidly absorbed systemically, and small increases in the dose level were lethal. Intravenous doses were rapidly cleared from the blood at lower levels, and upon escalation, were toxic with a high proportion of the dose accumulating within the lung tissue. To improve biocompatibility and prolong its circulation within the blood, IDR-1002 was further formulated onto high molecular weight hyperbranched polyglycerol (HPG) polymers. Constructs prepared at 5:1 and 10:1 peptide-to-polymer ratios were colloidally stable, maintained the biological profile of the peptide payload and helped reduce red blood cell lysis. The 5:1 construct circulated well in the blood, but higher peptide loading was associated with rapid clearance by the reticuloendothelial system. Many peptides face pharmacokinetic and biocompatibility challenges, but formulations such as those with HPG have the potential to overcome these limitations.
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This article is cited by 1 publications.
- Tullio V.F. Esposito, Cristina Rodríguez-Rodríguez, Colin Blackadar, Sylvia Kłodzińska, Hanne Mørck Nielsen, Katayoun Saatchi, Urs O. Häfeli. Biodistribution of the cationic host defense peptide LL-37 using SPECT/CT. European Journal of Pharmaceutics and Biopharmaceutics 2024, 202 , 114398. https://doi.org/10.1016/j.ejpb.2024.114398
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