Intranasal absorption of angiopeptin: in vitro study of absorption and enzymatic degradation

Abstract

The enzymatic degradation and absorption of angiopeptin (an octapeptide) were studied in vitro. Human nasal wash, rabbit nasal homogenate and supernatant were used as enzyme preparations and the Ussing chamber was used for the absorption studies. No enzymatic degradation was observed as degradation rates of 0.020 μg/h in human nasal wash, 0.046 μg/h in rabbit nasal homogenate and 0.054 μg/h in supernatant, the initial concentration being 0.20 μg/ml, were the same or lower than those observed in control experiments. Degradation is probably caused by hydrolysis, only. The appearance rate (mean ± S.D.) of angiopeptin from an aqueous solution was 1.82 ± 0.93 μg/h, equivalent to an apparent permeability coefficient of 9.1 × 10−7 cm/s. Addition of 1% glycocholate (GC) enhanced the appearance rate significantly by a factor of 2.7 (p < 0.05), whereas no effect was observed after addition of 1 or 5% glycofurol 75 (GF). Short-circuit current and potential difference were measured throughout the penetration study. Addition of 1% GC or 5% GF resulted in significant changes (p < 0.001) in electrophysiological properties of the tissue, whereas no changes were observed for 1% GF and control. All in all, the experiments have indicated that angiopeptin is a potential candidate for intranasal application.