Enhanced nasal absorption of hydrophilic markers after dosing with AT1002, a tight junction modulator

AT1002 is a six-mer synthetic peptide, H-FCIGRL-OH, that retains the delta G and Zot biological activity of reversibly opening tight junctions and increases the paracellular transport of drugs. The objective of this study was to evaluate the possible use of AT1002 in enhancing the nasal availability of macromolecules using large paracellular markers as model agents. Male Sprague–Dawley rats cannulated in the jugular vein were randomly assigned to receive radiolabelled paracellular markers, [¹⁴C]PEG4000 or [¹⁴C]inulin, with/without AT1002, for each intranasal study. The plasma concentration of PEG4000 with AT1002 (10 mg/kg) was significantly higher than that from PEG4000 control over 360 min following intranasal administration. The AUC_0–360 min and C_max from the PEG4000/AT1002 (10 mg/kg) treatment were statistically (p < 0.05) increased to 235% and 357%, of control, respectively. When inulin was administered with AT1002 (10 mg/kg), the plasma concentration was significantly higher (p < 0.05) than control over 360 min, and increases (p < 0.05) of 292% and 315% for AUC_0–360 min and C_max over control were observed, respectively. AT1002 significantly increased the nasal absorption of molecular weight markers, PEG4000 and inulin. This study suggests that AT1002 may be used to enhance the systemic availability of macromolecules when administered concurrently.