Macromolecular drugs oral administration

Considering patient acceptability and ease of administration, there is no doubt that oral administration is the most favored route, even if there have been reports on successful delivery of macromolecular drugs across nonperoral mucosal routes.6 7 Despite such advantages in oral administration, various barriers are encountered in the gastrointestinal (GI) tract that should be surmounted in order to gain sufficient bioavailability of... 

Physical barrier. Following oral administration of macromolecular drugs, their potential absorption pathways from the intestinal lumen to the bloodstream can be classified into transcellular transport associated with adsorptive or receptor-mediated endocytosis and paracellu-lar transport (Fig. 10.1). The GI tract surface consists of a tightly bound single layer of epithelial cells covered with thick and viscous mucus, which serves as a defensive deterrent against permeation of xenobi-otics and harmful pathogens. The epithelial cells in the GI tract are... 

Permeation of macromolecules through the GI epithelial cells after oral administration has been reported by several research groups. We have also confirmed the permeation of the hydrophilic macromolecules by using Caco-2 cells (Nagata et al. 2006). However, there are no data clearly showing the actual absorption of macromolecular drugs into the GI tract after oral administration. 

The enzymatic barrier is based on various classes of enzymes including proteases/peptidases, nucleases, glycosidases and lipases. Taking the most important macromolecular drugs into consideration, which are likely candidates for oral administration, the enzymatic barrier is primarily represented by proteases/ peptidases and nucleases. Proteases/peptidases are on the one hand based on luminally secreted proteases including pepsin,... 

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