Large molecule and particulate uptake in the nasal cavity: the effect of size on nasal absorption

One of the characteristics influencing the increased interest in the nasal cavity as a site for systemic drug delivery is the ability of large molecules to permeate through the nasal mucosa into the systemic circulation. Compilations of data regarding the absorption of large therapeutic agents, peptides and proteins in particular, along with more systematic studies using polymeric compounds have shown that for compounds larger than 1000 Da, bioavailability can be directly predicted from a knowledge of molecular weight. In general, the bioavailability of these large molecules ranges from 0.5 to 5%. Particulate uptake also occurs in the nasal mucosa, and particles up to approximately 1 µm have been shown to rapidly enter the bloodstream following intranasal administration. The unique barrier properties of this mucosal delivery site give it great promise as a route for the systemic administration of large molecules.