Biodistribution of Native and Nanoformulated Innate Defense Regulator Peptide 1002

Area of Science:

• Pharmacology
• Biomedical Engineering
• Immunology

Background:

• Innate defense regulator-1002 (IDR-1002) is a synthetic peptide with known immunomodulatory and antibiofilm properties.
• Its efficacy in infection and inflammation models is established, but its in vivo pharmacokinetic profile remains largely uncharacterized.

Purpose of the Study:

• To comprehensively assess the biodistribution, absorption, distribution, and excretion of IDR-1002 in live organisms.
• To evaluate the impact of different administration routes and doses on IDR-1002's behavior.
• To investigate the potential of hyperbranched polyglycerol (HPG) polymer formulation to enhance IDR-1002's pharmacokinetic and biocompatibility profile.

Main Methods:

• Gallium-67 radiolabeled IDR-1002 was used for nuclear tracing to track biodistribution.
• The peptide was administered via intravenous, peritoneal, subcutaneous, and intratracheal routes at various dose levels.
• IDR-1002 was formulated with HPG polymers at different peptide-to-polymer ratios (5:1 and 10:1) and evaluated for colloidal stability, biological activity, and red blood cell lysis.

Main Results:

• IDR-1002 was well-tolerated at subcutaneous and intraperitoneal doses, but higher doses showed delayed absorption and precipitation.
• Low intratracheal doses were rapidly absorbed, while higher doses were lethal; intravenous administration led to rapid blood clearance at low doses and toxicity with lung accumulation at higher doses.
• HPG-formulated IDR-1002 constructs were colloidally stable, maintained peptide activity, and reduced red blood cell lysis. The 5:1 construct showed good circulation, whereas higher loading resulted in rapid clearance by the reticuloendothelial system.

Conclusions:

• IDR-1002 exhibits route- and dose-dependent pharmacokinetics and toxicity.
• HPG polymer formulation represents a promising strategy to improve IDR-1002's biocompatibility and prolong its circulation, addressing common challenges with peptide therapeutics.