Evaluation of Sucrose Laurate as an Intestinal Permeation Enhancer for Macromolecules: Ex Vivo and In Vivo Studies

Evaluation of Sucrose Laurate as an Intestinal Permeation Enhancer for Macromolecules: Ex Vivo and In Vivo Studies

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Oral delivery of macromolecules requires permeation enhancers (PEs) adaptable to formulation.Sucrose laurate (SL) (D1216), a food grade surfactant, was assessed in Caco-2 monolayers, isolated rat intestinal tissue mucosae, and rat intestinal instillations.Accordingly, 1 mM SL increased the apparent permeability coefficient (Papp) of [14C]-mannitol and reduced transepithelial electrical resistance (TEER) across monolayers.It altered expression of the tight junction protein, ZO-1, increased plasma membrane potential, and decreased mitochondrial membrane potential in Caco-2 cells.The concentrations that increased flux were of the same order as AEG FEB52600ZM 60cm Semi Integrated Dishwasher those that induced cytotoxicity.

In rat colonic tissue mucosae, the same patterns emerged in respect to the concentration-dependent increases in paracellular marker fluxes and TEER reductions with 5 mM being the key concentration.While the histology revealed some perturbation, ion transport capacity was retained.In rat Console and Display Board jejunal and colonic instillations, 50 and 100 mM SL co-administered with insulin induced blood glucose reductions and achieved relative bioavailability values of 2.4% and 8.9%, respectively, on a par with the gold standard PE, sodium caprate (C10).

The histology of the intestinal loops revealed little damage.In conclusion, SL is a candidate PE with high potential for emulsion-based systems.The primary action is plasma membrane perturbation, leading to tight junction openings and a predominant paracellular flux.