دورية أكاديمية
Biodistribution of Native and Nanoformulated Innate Defense Regulator Peptide 1002.
| العنوان: | Biodistribution of Native and Nanoformulated Innate Defense Regulator Peptide 1002. |
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| المؤلفون: | Esposito TVF; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada., Blackadar C; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada., Wu L; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada.; Wuya College of Innovation, Shenyang Pharmaceutical University, Wenhua Road No. 103, Shenyang 110016, China., Rodríguez-Rodríguez C; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada.; Department of Physics and Astronomy, Faculty of Science, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada., Haney EF; Centre for Microbial Disease and Immunity Research, Department of Microbiology and Immunology, Faculty of Science, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada.; Asep Medical Holdings, 420 - 730 View Street, Victoria V8W 3Y7, British Columbia, Canada., Pletzer D; Centre for Microbial Disease and Immunity Research, Department of Microbiology and Immunology, Faculty of Science, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada.; Department of Microbiology and Immunology, University of Otago, Dunedin 9054, New Zealand., Saatchi K; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada., Hancock REW; Centre for Microbial Disease and Immunity Research, Department of Microbiology and Immunology, Faculty of Science, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada., Häfeli UO; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver V6T 1Z4, British Columbia, Canada.; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 1172, Denmark. |
| المصدر: | Molecular pharmaceutics [Mol Pharm] 2024 Jun 03; Vol. 21 (6), pp. 2751-2766. Date of Electronic Publication: 2024 May 01. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101197791 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1543-8392 (Electronic) Linking ISSN: 15438384 NLM ISO Abbreviation: Mol Pharm Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Chemical Society, c2004- |
| مواضيع طبية MeSH: | Antimicrobial Cationic Peptides*/pharmacokinetics , Antimicrobial Cationic Peptides*/chemistry , Nanoparticles*/chemistry, Animals ; Female ; Male ; Mice ; Gallium Radioisotopes/pharmacokinetics ; Gallium Radioisotopes/chemistry ; Gallium Radioisotopes/administration & dosage ; Immunity, Innate/drug effects ; Lung/metabolism ; Lung/drug effects ; Mice, Inbred C57BL ; Tissue Distribution |
| مستخلص: | 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. |
| فهرسة مساهمة: | Keywords: IDR-1002; SPECT/CT; biodistribution; hyperbranched polyglycerol; nuclear tracing; peptide; radiolabeled peptide; radiotracer |
| المشرفين على المادة: | 0 (Antimicrobial Cationic Peptides) 0 (Gallium Radioisotopes) 4LJK511Z86 (Gallium-67) |
| تواريخ الأحداث: | Date Created: 20240502 Date Completed: 20240603 Latest Revision: 20240829 |
| رمز التحديث: | 20240830 |
| DOI: | 10.1021/acs.molpharmaceut.3c01169 |
| PMID: | 38693707 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1543-8392 |
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| DOI: | 10.1021/acs.molpharmaceut.3c01169 |