European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.VMay 11, 2020

Comparing how two intestinal absorption boosters, SNAC and sodium caprate, help substances pass through the gut lining

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 1, 2026

Abstract

C (8.5 mM) reversibly reduced transepithelial electrical resistance and increased FD4 permeability across Caco-2 monolayers.

C induced reorganization of three tight junction proteins, while SNAC only affected claudin-5 localization.
High concentrations of both C and SNAC were needed to produce end-point toxicology changes in vitro.
SNAC was less effective than C at inducing changes in lysosomal and nuclear structures and plasma membrane integrity.
Both agents exhibited detergent-like properties, indicating initial membrane fluidization followed by alterations in cellular parameters.
Increased FD4 permeability in monolayers in response to C was associated with concentrations that also affected cytotoxicity and high content analysis parameters.
While these in vitro findings clarify their epithelial mechanisms, clinical observations suggest potential overestimation of their toxicity in the intestinal environment.

Simplified

Salcaprozate sodium (SNAC) and sodium caprate (C) are the two leading intestinal permeation enhancers (PEs) in oral peptide formulations in clinical trials. There is debate over their mechanism of action on intestinal epithelia. The aims were: (i) to compare their effects on the barrier function by measuring transepithelial electrical resistance (TEER), permeability of FITC-4000 (FD4) across Caco-2 monolayers, and on immunohistochemistry of tight junction (TJ)-associated proteins; and (ii) to compare cellular parameters using conventional end-point cytotoxicity assays and quantitative high content analysis (HCA) of multiple sub-lethal parameters in Caco-2 cells. C(8.5 mM) reversibly reduced TEER and increased FD4 permeability across monolayers, whereas SNAC had no effects on either parameter except at cytotoxic concentrations. Cexposure induced reorganization of three TJ proteins, whereas SNAC only affected claudin-5 localization. High concentrations of Cand SNAC were required to cause end-point toxicology changes in vitro. SNAC was less potent than Cat inducing lysosomal and nuclear changes and plasma membrane perturbation. In parallel, HCA revealed that both agents displayed detergent-like features that reflect initial membrane fluidization followed by changes in intracellular parameters. In conclusion, FD4 permeability increases in monolayers in response to Cwere in the range of concentrations that altered end-point cytotoxicity and HCA parameters. For SNAC, while HCA parameters were also altered in a similar overall pattern as C, they did not lead to increased paracellular flux. These assays show that both agents are primarily surfactants, but Chas additional TJ-opening effects. While these in vitro assays illucidate their epithelial mechanism of action, clinical experience suggests that they over-estimate their toxicology in the dynamic intestinal environment. 10 10 10 10 10 10 10 10

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Competing interests

Declaration of Competing Interest DB consults on oral peptide research for Pharma companies. BI is an employee of Sanofi-Aventis (Montpellier, France). CT is currently an employee of Alk-Abello Ltd (Paris).

PubMed

Comparing how two intestinal absorption boosters, SNAC and sodium caprate, help substances pass through the gut lining

Abstract

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Abstract

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