Further analysis of transcytosis of free polypeptides and polypeptide-coated nanobeads in rabbit nasal mucosa.

Abstract

In rabbit nasal mucosa, free polypeptides and polypeptide-coated nanospheres are actively absorbed by the M cells present in specialized areas of the epithelium. Because polypeptide-coated nanosphere transport was abolished in the presence of free polypeptides, free polypeptides and polypeptide-coated nanospheres are shown here to compete. Fluxes of polypeptide-coated nanospheres with 356, 490, and 548 nm diameters have been compared. BSA-coated beads were poorly transported, at the same rate, when bead diameters were 356 or 490 nm [net flux of approximately 2-2.5 x 10(6) nanospheres (nan). cm(-2) x h(-1)]; however, their net transport largely increased toward a value of 25 x 10(6) nan. cm(-2) x h(-1) at a diameter of 548 nm. Insulin-coated beads displayed a net flux that was significantly higher than BSA-coated beads but equally were transported at the same rate (net flux of approximately 8.0 x 10(6) nan. cm(-2) x h(-1)) at diameters of 356 or 490 nm; once again, their net flux significantly increased toward a value of 25 x 10(6) nan. cm(-2) x h(-1), if the bead diameter was 548 nm. Insulin plus anti-insulin IgG-coated 490-nm-diameter beads displayed a very high net flux, although not yet saturating (approximately 60 x 10(6) nan. cm(-2) x h(-1)); however, a significantly lower saturated net flux (once again approximately 25 x 10(6) nan. cm(-2) x h(-1)) was shown with 548-nm-diameter beads. In conclusion, 1) in the range of 356-490 nm diameter, net transport was independent of bead diameter and, conversely, largely dependent on the coating polypeptides, and 2) at 548 nm diameter, nanospheres tended to be transferred at similar rates independently of coating kind and the maximal net transport capacity of the mucosa was reduced. The suspension viscosity largely increased with 548-nm polypeptide-coated nanospheres; this fact is hypothetically proposed to be the cause of these events.