Neuroprotection against apoptosis of SK-N-MC cells using RMP-7- and lactoferrin-grafted liposomes carrying quercetin.
A drug delivery system of quercetin (QU)-encapsulated liposomes (LS) grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf) was developed to permeate the blood-brain barrier (BBB) and rescue degenerated neurons, acting as an Alzheimer's disease (AD) pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS) was used to traverse human brain microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ) fibrils. We found that surface RMP-7 and Lf enhanced the ability of QU to cross the BBB without inducing strong toxicity and damaging the tight junction. In addition, RMP-7-Lf-QU-LS significantly reduced Aβ-induced neurotoxicity and improved the viability of SK-N-MC cells. Compared with free QU, RMP-7-Lf-QU-LS could also significantly inhibit the expression of phosphorylated c-Jun N terminal kinase, phosphorylated p38, and phosphorylated tau protein at serine 202 by SK-N-MC cells, indicating an important role of RMP-7, Lf, and LS in protecting neurons against apoptosis. RMP-7-Lf-QU-LS is a promising carrier targeting the BBB to prevent Aβ-insulted neurodegeneration and may have potential in managing AD in future clinical applications.
['Kuo|Yung-Chih|YC|', 'Tsao|Chien-Wei|CW|']
D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D017209:Apoptosis D001253:Astrocytes D001812:Blood-Brain Barrier D001920:Bradykinin D001921:Brain D045744:Cell Line, Tumor D002478:Cells, Cultured D016503:Drug Delivery Systems D042783:Endothelial Cells D004730:Endothelium, Vascular D006801:Humans D007781:Lactoferrin D008081:Liposomes D018696:Neuroprotective Agents D010446:Peptide Fragments D011794:Quercetin
pharmacotherapy β-amyloid neurodegeneration Alzheimer’s disease blood–brain barrier drug targeting