“Oil-soluble” reversed lipid nanoparticles for oral insulin delivery

BACKGROUND: In this study, we aimed to design a novel oral insulin delivery system, named “oil-soluble” reversed lipid nanoparticles (ORLN), in which a hydrophilic insulin molecule is encapsulated by a phospholipid (PC) shell and dissolved in oil to prevent the enzymatic degradation of insulin. ORLN was characterized by transmission electron microscopy and dynamic light scattering. RESULTS: In vitro enzymatic stability studies showed higher concentrations of insulin in cells incubated with ORLN-encapsulated insulin than in those incubated with free insulin solution in artificial intestinal fluid (pH 6.5). The protective effect of ORLN was attributed to its special release behavior and the formulation of the PC shell and oil barrier. Furthermore, an in vivo oral efficacy study confirmed that blood glucose levels were markedly decreased after ORLN administration in both healthy and diabetic mice. In vivo pharmacokinetic results showed that the bioavailability of ORLN-conjugated insulin was approximately 28.7% relative to that of the group subcutaneously administered with an aqueous solution of insulin, indicating enhanced oral absorption. CONCLUSIONS: In summary, the ORLN system developed here shows promise as a nanocarrier for improving the oral absorption of insulin.