Peptides transport across Caco-2 cells

Conradi RA, AR Hilgers, NFH HO, PS Burton. (1991). The influence of peptide structure on transport across Caco-2 cells. Pharm Res 8 1453-1460. 

Zhu XL, Watanabe K, Shiraishi K, Ueki T, Noda Y, Matsui T, Matsumoto K. (2008) Identification of ACE-inhibitory peptides in salt-free soy sauce that are transportable across caco-2 cell monolayers. Peptides 29 338-344. 

Tab. 4.4 Structures of the peptide used to study the influence of bond modification on transport across Caco-2 cells [36]...

Conradi RA, Hilgers AR, Ho NFH, and Burton PS. The Influence of Peptide Structure on Transport Across Caco-2 cells. Pharm Res 1991 8 1453—1460. 

R. T., Acyloxyalkoxy-based cyclic prodrugs of opioid peptides evaluation of their chemical and enzymatic stability as well as their transport properties across Caco-2 cell mono-layers, Pharm. Res., 1999, 36, 24-29. 

Although there is a widespread perception that wild-type MDCK cells contain insignificant levels of P-gp to affect substrate transport, it has been demonstrated that this is not the case. It was shown that the transport of vinblastine sulfate across MDCK monolayers was indeed apically polarized (203). These results were duplicated by Hirst et al. using the same test compound, verapamil, in two different strains of MDCK cells. The transport profiles of verapamil showed polarity in both a high-resistance strain [TEER 2000 Q-cm2 and a low-resistance strain (TEER < 200 Q-cm2] (365). Recently, parallel studies were performed measuring the transport of a novel peptide, K02, across both MDCK and Caco-2 cells (364). The results showed nearly identical profiles for the AP to BL and BL to AP transport of this agent in both cell types. Although it is unlikely that all P-gp substrates will behave identically in both cell lines, these studies indicate that there is sufficient P-gp expression in MDCK cells to affect transport studies. Thus, MDCK cells can be used to evaluate the transport of compounds that are suspected to be substrates of P-gp. 

The effect of size and charge on the passive diffusion of peptides across Caco-2 cell monolayers via paracellular pathways as well as on retention time has been studied using the IAM technique [38]. It was found that a positive net charge of the hydrophilic peptides favors permeation across the intestinal mucosa via the paracellular pathway. With an increase in size, the molecular sieving of the epithelial membrane dominates the transport of peptides and the influence of the net charge becomes less important. The permeability coefficient, Papp, of the capped amino acids and the model peptides can be calculated by ... 

Putnam, W.S., Pan, L., Tsutsui, K., Takahashi, L. and Benet, L.Z. (2002) Comparison of bidirectional cephalexin transport across MDCK and caco-2 cell monolayers interactions with peptide transporters. Pharmaceutical Research, 19, 27-33. 

Putnam WS, Pan L, Tsutsui K, Takahashi L, and Benet LZ. Comparison of Bidirectional Cephalexin Transport Across MDCKand Caco-2 Cell Monolayers Interactions with Peptide Transporters. Pharm Res 2002a 19 27-33. 

Synthetic peptides regulate the paracellular transport of dextrans across Caco-2 cell monolayers... 

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