Transport of human growth hormone across Caco-2 cells with novel delivery agents: evidence for P-glycoprotein involvement.

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Wu SJ, Robinson JR

Transport of human growth hormone across Caco-2 cells with novel delivery agents: evidence for P-glycoprotein involvement.

J Control Release. 1999 Nov 1;62(1-2):171-7. doi: 10.1016/s0168-3659(99)00035-8.

PubMed ID

10518648 [ View in PubMed

]

Abstract

Emisphere Technologies, Inc. has synthesized a series of small molecules which have been shown to improve protein absorption through mucosal tissue. This enhancement is specific between protein and a particular delivery agent. Despite the specificity of interaction, the mechanism of enhanced tissue penetration is still unclear. The purpose of this work is to understand the enhancement mechanism(s) of these delivery agents by using Caco-2 cells as a model membrane. It was found that the bidirectional transepithelial fluxes of human growth hormone (hGH) in the presence of these delivery agents across human intestinal epithelial Caco-2 cell line showed marked asymmetry. Average permeability coefficient values obtained in the apical (AP) to basolateral (BL) direction were lower than those of the reverse (BL to AP) direction. On the other hand, the fluxes for human growth hormone alone were symmetric. When P-glycoprotein inhibitors were included in the transport medium, the permeability coefficient values of BL to AP direction were significantly decreased while the transport was increased in the reverse direction in the presence of delivery agents. P-glycoprotein inhibitors had no effect on the transport of human growth hormone alone. This study shows that human growth hormone alone can be transported across Caco-2 cells in very limited quantities by passive diffusion, but in the presence of delivery agents, human growth hormone can be effluxed in a P-glycoprotein-mediated fashion. This also indirectly shows that the human growth hormone has become more lipophilic in the presence of delivery agents.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Lonapegsomatropin	ATP-dependent translocase ABCB1	Protein	Humans	Unknown	Substrate	Details
Somatotropin	ATP-dependent translocase ABCB1	Protein	Humans	Unknown	Substrate	Details