Targeted solid lipid nanoparticles with peptide ligand for oral delivery of atorvastatin calcium

Abstract

Feasible and effective peptide ligand-modified solid lipid nanoparticles (SLNs) have been designed to improve the oral bioavailability of atorvastatin calcium (ATC). In the present work, the peptide ligand-modified SLNs loaded with ATC, namely ATC CSK-SLNs, were prepared by coupling the peptide ligand CSKSSDYQC (CSK), which showed affinity with goblet cells, to stearic acid. The physicochemical properties of the SLNs were characterized by TEM, DSC and FT-IR, which unravelled the transformation of ATC to an amorphous or molecular state from the native crystalline form. Compared with unmodified SLNs, the CSK-SLNs exhibited a more efficient cellular uptake across the Caco-2/HT29 co-cultured cell monolayer as evidenced by confocal laser microscopy. Following absorption, the mechanisms were studied using a modified in situ perfusion method in rats, which showed the segment-dependent absorption characteristics of ATC, ATC SLNs as well as ATC CSK-SLNs. The K_a (0.076 ± 0.23 min⁻¹) and P_app (0.011 ± 0.63 cm min⁻¹) values of the ATC CSK-SLNs were raised 2.97-fold and 2.99-fold in comparison with those of the ATC solution, implying that CSK peptide modification enhances the permeation of drugs across the epithelium. In conclusion, our results demonstrated that CSK-modified SLNs could be potential carriers for the transport of drugs across intestinal barriers.