Orally Delivered Salmon Calcitonin-Loaded Solid Lipid Nanoparticles Prepared by Micelle–Double Emulsion Method Via The Combined Use of Different Solid Lipids

Abstract

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: The SLNs formed by SA and TP as the solid lipids may be a promising carrier for oral delivery of peptide drugs.

Original submitted 1 February 2012; Revised submitted 10 August 2012; Published online 17 October 2012

Keywords::

• bioavailability
• combined solid lipid
• micelle–double emulsion technique
• salmon calcitonin
• solid lipid nanoparticle
• uptake

Financial & competing interests disclosure

This research was supported by the 11th Five-Year Plan National Key Technology Research and Development Program for New Drug R&D (2009ZX09503-026), the National Natural Science Foundation of China (81173010) and National Basic Research Program of China (973 Program, 2009CB903300). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This research was supported by the 11th Five-Year Plan National Key Technology Research and Development Program for New Drug R&D (2009ZX09503-026), the National Natural Science Foundation of China (81173010) and National Basic Research Program of China (973 Program, 2009CB903300). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.