Development and evaluation of insulin-loaded cationic solid lipid nanoparticles for oral delivery

Cationic solid lipid nanoparticles (cSLN) loaded with insulin for oral delivery were prepared by the so-called water-in-oil-in-water double emulsion technique. The lipid matrix was composed of glyceryl palmitostearate and 1,2-dioleoyl-3-trimethylammonium-propane as a cationic lipid. Depending on the formulation, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] was incorporated to decrease the adsorption of insulin onto the surface of the nanoparticles. This aimed to achieve a positive zeta potential to obtain bioadhesion properties. The cSLN were characterized by a Z-average lower than 300 nm and by a zeta potential higher than 33 mV. The loading efficiency was ranged between 30% and 42%. It was shown that all the nanoparticles developed were able to fix solubilized mucin, which was used to evaluate bioadhesion properties. The cSLN also allowed the encapsulated insulin to be protected from the enzymatic activity of both pepsin and trypsin. The dissolution profiles of the insulin from the cSLN were characterized by a biphasic release. There was an initial burst release in the first 30 min, followed by a sustained release of the peptide. Moreover, compared to free insulin in solution, the cSLN developed significantly increased the passage of the encapsulated insulin through a monolayer of co-cultured Caco-2/HT29 cells. This went from 1.16 ± 0.27% to 2.89 ± 0.39% after 4 h, for the free insulin and the cSLN respectively.