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Aim:To develop a stable self-emulsifying formulation for oral delivery of insulin.Methods:Caco-2 cell line and diabetic beagles were used as in vitro and in vivomodels to study the absorption mechanism and the hypoglycemic efficacy of theformulation.In addition,various physicochemical parameters of the formulationsuch as droplet size,insulin encapsulation efficiency and stability were evaluated.Results:This formulation enabled changes in barrier properties of Caco-2monolayers,as referred by transepithelial electrical resistance(TEER)and appar-ent permeability coefficients(P_(app))of the paracellular marker ranitidine(20-foldgreater than control)but not transcellular marker propranolol,suggesting that theopening of tight junctions was involved.In diabetic beagle dogs,the bioavailabilityof this formulation was up to 15.2% at a dose of 2.5 IU/kg in comparison with thehypoglycemic effect of native insulin(0.5 IU/kg)delivered by subcutaneousinjection.Conclusion:This formulation,recently approved by the China StateFood and Drug Administration to enter clinical trials,was stable,degradation-protected and absorption-enhanced,and provided a promising formulation fororal insulin delivery.
Aim: To develop a stable self-emulsifying formulation for oral delivery of insulin. Methods: Caco-2 cell line and diabetic beagles were used as in vitro and in vivomodels to study the absorption mechanism and the hypoglycemic efficacy of the formulation. In addition, various Results: This formulation enables changes in barrier properties of Caco-2monolayers, as referred to by transepithelial electrical resistance (TEER) and appar-ent permeability coefficients (P_ (app ) of the paracellular marker ranitidine (20-foldgreater than control) but not transcellular marker propranolol, suggesting that theopening of tight junctions was involved. diabetic beagle dogs, the bioavailabilityof this formulation was up to 15.2% at a dose of 2.5 IU / kg in comparison with the hypoglycemic effect of native insulin (0.5 IU / kg) delivered by subcutaneous injection .Conclusion: This formulation, recently app roved by the China State Food and Drug Administration to enter clinical trials, was stable, degradation-protected and absorption-enhanced, and provided a promising formulation fororal insulin delivery.