Solid lipid nanoparticles modified with stearic acid–octaarginine for oral administration of insulin

Abstract

The aim of this study was to design and characterize solid lipid nanoparticles (SLNs) modified with stearic acid–octaarginine (SA-R₈) as carriers for oral administration of insulin (SA-R ₈-Ins-SLNs). The SLNs were prepared by spontaneous emulsion solvent diffusion methods. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the SA-R₈-Ins-SLNs were 162 nm, 29.87 mV, 3.19%, and 76.54%, respectively. The zeta potential of the SLNs changed dramatically, from −32.13 mV to 29.87 mV, by binding the positively charged SA-R₈. Morphological studies of SA-R₈-Ins-SLNs using transmission electron microscopy showed that they were spherical. In vitro, a degradation experiment by enzymes showed that SLNs and SA-R₈ could partially protect insulin from proteolysis. Compared to the insulin solution, the SA-R₈-Ins-SLNs increased the Caco-2 cell’s internalization by up to 18.44 times. In the in vivo studies, a significant hypoglycemic effect in diabetic rats over controls was obtained, with a SA-R₈-Ins-SLN pharmacological availability value of 13.86 ± 0.79. These results demonstrate that SA-R₈-modified SLNs promote the oral absorption of insulin.

Keywords:

• solid lipid nanoparticles
• cell penetration peptides
• stearic acid octaarginine
• insulin
• oral administration

Acknowledgments

The National Natural Science Foundation of China (No 30901867 and No 30973649) is gratefully acknowledged for financial support. This work was also supported by the Research Fund for the Doctoral Program of Higher Education of China (No 20090096110002) and the Fundamental Research Funds for the Central University (JKQ2011016).

Disclosure

The authors report no conflicts of interest in this work.