Multiple-component dual-phase solid lipid nanoparticles with conjugated transferrin for formulating antioxidants and nerve growth factor against neuronal apoptosis

摘要

Internal aqueous phase was incorporated in solid lipid nanoparticles (SLNs) containing 5 lipid components to form dual-phase SLNs (DPSLNs), which were then conjugated with transferrin (TO to transport nerve growth factor (NGF), rosmarinic acid (ROA), curcumin (CURC) and quercetin (QU) for enhanced activity against neuronal apoptosis. Particle size, physical stability, loading rate of drugs and releasing rate of drugs were measured to determine the most appropriate lipid composition of DPSLNs. The results showed that DPSLNs not only acted as a drug carrier, but also served to decrease drug-induced cytotoxicity to blood-brain barrier (BBB) cells through sustained release. QU-CURC-ROA-NGF-DPSLNs with modified Tf on the surface facilitated the capacity of drugs to infiltrate the BBB. Interaction between lecithin and Tf assisted in BBB-targeting ability of DPSLNs. Moreover, addition of cardiolipin in DPSLNs improved the therapeutic efficacy via recognizing beta-amyloid around neurons. Combining QU, CURC, ROA and NGF in DPSLNs promoted their roles in the reduction of neurotoxicity by mutual collaboration. Immunofluorescence and western-blot analysis revealed suppressed expressions of caspase-3, extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N terminal kinase and p38, and enhanced expressions of cAMP-response element-binding protein (CREB) and ERK5 after treatment with QU-CURC-ROA-NGF-DPSLNs. Hence, the drug-loaded DPSLNs with grafted Tf can be promising in rescuing degenerated neurons for Alzheimer's disease therapy. (C) 2020 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.