Surface modification of nanostructure lipid carrier (NLC) by oleoyl-quaternized-chitosan as a mucoadhesive nanocarrier

Abstract A nanostructure lipid carrier (NLC) composed of solid, and liquid lipid as a core has been developed as a delivery system for hydrophobic drug molecules. The aim of this research was to fabricate an oleoyl-quaternized-chitosan (CS)-coated NLC, where the mucoadhesive property of nanoparticles is enhanced for more efficient drug delivery. NLC loaded with alpha-mangostin (AP), a model hydrophobic drug, were fabricated using a high pressure homogenization process and subsequently coated with CS. The fabricated nanoparticles showed particle sizes in the range of 200–400 nm, with low polydispersity, high physical stability and excellent encapsulation efficiency (EE > 90%). Additionally, in vitro viability, cytotoxicity and ability of NLC and CS-NLC to affect apoptosis in carcinoma Caco-2 cells were determined using the Triplex assay. Gene expressiom analysis were performed using quantitative reverse transcription Polymerase Chain Reaction (RT-qPCR). Moreover, in vivo toxicological testing of NLCs was conducted in zebrafish embryos. Results indicated that CS-NLC provieded high cytotoxicity than NLC itself. In the case of AP loaded nanoparticles, NLC loaded with AP (AP-NLC), and CS-NLC loaded with AP (CS-AP-NLC) exhibited higher cytotoxicity to Caco-2 over Hela cells. These results indicate that CS-NLC shows enhanced cellular uptake but increased cytotoxicity characteristics over NLC and therefore careful optimization of dosage and loading levels in CS-NLC is needed to allow cancer cell targeting, and for exploiting the potential of these systems in cancer therapy.