Pharmacokinetics and Tissue Distribution of Fluorescently Labeled Neoagarotetraose in Mice

Background/Objectives: Neoagarotetraose (NA4), a marine-derived tetrasaccharide, holds promise as an anti-inflammatory and antioxidant agent; however, its oral bioavailability and systemic exposure mechanisms require elucidation. Methods: This study characterizes the biopharmaceutical profile of NA4 after oral and intravenous administration using a validated near-infrared fluorescence method based on covalent conjugation with Cy7. Results: Following oral gavage (200 mg/kg), NA4-Cy7 was rapidly absorbed (Tmax: 1.0 h; Cmax: 35.6 mg/L), with prolonged systemic exposure (mean residence time: 13.1 h) and an elimination half-life of 8.9 h. Intravenous administration (25 mg/kg) revealed a low volume of distribution at steady state (Vss: 0.0132 L/kg) and a shorter MRT (4.3 h). Tissue distribution at 24 h showed preferential accumulation in the kidney, liver, and lung, with direct visualization of intact NA4 crossing the intestinal epithelium. Conclusions: These findings demonstrate that fluorescently labeled NA4-Cy7 can cross the intestinal epithelial barrier and reach systemic circulation, supporting its potential as an orally active agent with organ-specific targeting properties.