Drug Physicochemical Properties

The physicochemical properties of the drug can have a profound impact on the performance of the drug delivered by the IN route. For a comprehensive review in this area, the reader is referred to elsewhere (19). For the purposes of the current chapter, a paramount consideration for peptides and proteins is their relatively large molecular weight, which limits their transepithelial permeation. Even so, IN delivery of peptides and small proteins can be dramatically improved by employing permeation enhancers that are capable of opening TJs and promoting paracellular transport. It is critical that the permeation enhancers employed exhibit low nasal tissue cytotoxicity, maintain good cell viability, and provide for reversibility of TJs, as described elsewhere (19,75,76).

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