Orally delivered salmon calcitonin-loaded solid lipid nanoparticles prepared by micelle–double emulsion method via the combined use of different solid lipids

Aim: The purpose of this study was to develop a new orally delivered nanoparticulate system to improve the bioavailability of salmon calcitonin (sCT). Materials & methods: Four sCT-loaded solid lipid nanoparticles (SLNs) were prepared successfully by micelle–double emulsion technique via either the sole use of stearic acid (SA) or the combined use of SA and triglycerides (including tripalmitin [TP], trimyristin or trilaurin). Results: Compared with other SLNs, the combination of SA and TP could not only significantly improve the colloidal stability of SLNs and enhance the drug stability in the simulated intestinal fluids, but also intensively increase the intracellular uptake of drugs compared with the other SLNs (p < 0.05). The mechanism of internalization was an active transport involved in clathrin- and caveolae-dependent endocytosis. In vivo, the sCT SLNs prepared with SA and TP exhibited the highest reduction of plasma Ca2+ level (17.44 ± 3.68%) with a bioavailability of 13.01 ± 3.24%. Conclusion: Th...