The metabolic barrier of the lower intestinal tract of salmon to the oral delivery of protein and peptide drugs

Abstract

Oral delivery of peptide and protein drugs has potential advantages for the aquaculture industry. The bioavailability of proteins and peptides from the intestinal tract is very low. This can be attributed in part to the proteolytic activities of the intestine. Bovine serum albumin (BSA), human (hLHRH) and salmon (sLHRH) luteinizing-hormone releasing hormones were used to evaluate the proteolytic activity of anterior, middle and posterior sections of the Quinnat salmon ( Oncorhynchus tshawytscha) intestinal tract. The lumenal proteolytic activities of the posterior intestinal section towards BSA were approximately half that of the anterior and middle sections. The half-lives of the LHRH analogues in the posterior were twofold longer than for the anterior and middle sections. Proteolytic activity of the posterior mucosal homogenates towards BSA was fourfold higher than the middle mucosal homogenates. LHRH analogues were hydrolysed by the posterior mucosal homogenate, whereas in the middle mucosal homogenate they were stable. Soybean trypsin inhibitor was shown to be the most effective inhibitor of lumenal proteolytic activity towards LHRH analogues. Sodium deoxycholate, EDTA and bestatin significantly inhibited the posterior mucosal hydrolytic activity towards the LHRH analogues. The posterior intestine of salmon is the most favourable site for the delivery of BSA and LHRH analogues with respect to the lumen, however the higher proteolytic activity of the posterior mucosa has to be overcome.