Design of lipid modified polymeric nanoparticles for improvement of oral absorption of insulin

In this study, lipid modified polymeric nanoparticles for oral delivery of insulin was developed. Firstly, chitosan nanoparticles (CS NPs) was prepared by cross-linking of chitosan with triphosphate TPP as the core of the core-shell structured nanocarriers. Then lipid coating chitosan nanoparticles (LCS) was prepared by co-incubation of the CS NPs with EPC liposomes. The morphologies of these nanocarriers were observed using transmission electron microscope (TEM). These nanocarriers were also characterized in terms of the stability of insulin in the nanocarriers, mucus penetrating properties, and cellular association efficiencies. Under TEM a core-shell structure could be observed in LCS indicating CS NPs formed the core which was coated with lipids. LCS had an average diameter of 202 nm with a zeta potential of -7.1 mV. In vitro degradation study showed that with the phospholipids layer, LCS could protect the chitosan associated insulin from degradation by trypsin and α-chymotrypsin. Cellular association study performed on Caco-2 revealed that the cell association of LCS was slightly higher than CS NPs. However compared to CS NPs, LCS did not enhance mucus penetration properties in in vitro mucus penetration study. In summary, the core-shell structured nanocarriers present promising for effective oral insulin delivery by combining the effects of enhancing the stability of insulin in GI tract and enhanced cell association study. However, the functionality of the nanocarriers needs to be further improved by enhancing mucus penetration property.