Quercetin and Rosmarinic Acid Encapsulated Into Phosphatidic Acid Liposomes Grafted With Apolipoprotein E for Transporting across the In Vitro Blood–Brain Barrier and Protection of SK-N-MC Cells Against β-amyloid Peptide-Induced Degeneration

• Main Authors: Hung Tzu-Yu, 洪紫瑜
• Other Authors: Yung-Chih Kuo
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/9qmjju

碩士 === 國立中正大學 === 化學工程研究所 === 102 === Liposomes containing phosphatidic acid and with a modified ApoE peptide encapsulate quercetin and rosmarinic acid (RA) as drug carrier. Comparing the cellular uptake enhance effect of Tween 80 to ApoE. The cell co-culture model was established by consisting of human brain-microvascular endothelial cells (HBMECs), human brain vascular pericytes (HBVPs) and human astrocytes (HAs) to investigate quercetin and RA permeability of the in vitro blood–brain barrier (BBB) model, and then the protective effect of quercetin and RA against the in vitro Alzheimer’s disease (AD) neurodegenerative model was established by SK-N-MC neuroblastoma cell line with Aβ-induced neurotoxicity. The results indicated that an increase in PA mole percentage enhanced the particles size, absolute value of zeta potential, and the entrapment efficiency of quercetin and RA, however, reduced the release rate of quercetin and RA as well as loading efficiency of ApoE. The TEER value was 364 ± 10.4 Ω × cm2 and PI permeability across the BBB without nanocarriers was 2.0 ± 0.5 × 106 cm/s. The permeability of PA-ApoE liposomes was higher than non-modified liposomes. In vitro AD neurodegenerative model indicated that quercetin and RA encapsulated into liposomes can promote the viability and inhibit the apoptosis of SK-N-MC cells. Finally, the results of immunofluorescence demonstrated that conjugation of ApoE on liposomes can target HBMECs via LDL receptor to enhance the permeability against BBB and cellular uptake. Surface ApoE is efficient in transporting PA-liposomes across the BBB and inhibiting the degeneration of SK-N-MC cells with Aβ-induced neurotoxicity. Futhermore, in an AD mouse model by the intracerebroventricular injection of Aβ1–42, PA-ApoE liposomes significantly improved the cognitive ability along with increasing acetylcholinesterase activity and malondialdehyde level. Based on our findings, we conclude that PA-ApoE liposomes can be a promising delivery system for AD treatment in preclinical trials.