Synergic effect of ceftriaxone, FK506 and nilotinib encapsulated in glutathione-liposomes on regulation of overexpressed of α-synuclein, dopamine markers and apoptotic factors in dopaminergic neurons

• Main Authors: TSAI, HE-CHENG, 蔡和橙
• Other Authors: KUO, YUNG-CHIH
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/6rnz8g

碩士 === 國立中正大學 === 化學工程研究所 === 106 === The purpose of this study was to develop glutathione (GSH)-liposomes as a drug delivery system to carry ceftriaxone (CEF), FK506 and nilotinib across the blood‒brain barrier (BBB) and study their synergic effect on Parkinson’s disease (PD) treatment. Thin-film hydration method was utilized to prepare liposomes containing 1,2-distearoyl-sn-glycro-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol, dihexadecyl phosphate (DHDP) and cardiolipin (CL) and surface was modified with GSH. An increasing mole percentage of DHDP and CL increased the particles size and absolute value of zeta potential, along with improved entrapment efficiency and reduced releasing rate of CEF, FK506 and nilotinib. The protective effect of GSH-CEF-FK506-nilotinib-CL/liposomes against an in vitro PD neurodegenerative model established by SH-SY5Y neuroblastoma cells line with 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity was carried out. In vitro PD neurodegenerative model indicated that CEF, FK506 and nilotinib encapsulated liposomes promoted SH-SY5Y cells viability. Further, incorporation of CL into the liposomes enhanced the target efficiency. The western blot study showed that MPP+ enhanced the expression of α-synuclein, Bcl-2 associated X (Bax) and reduced the expression of B-cell lymphoma 2 (Bcl-2), tyrosine hydroxylase (TH) and dopamine transporter (DAT). However, treatment with different liposomes reduced the expression of α-synuclein and enhanced the expression of Bcl-2, TH and DAT. The synergetic effect arised from amalgamated activity of CEF, FK506 and nilotinib and α-synuclein targeting ability of CL augmented their therapeutic efficiency against an in vitro PD model. Hence, GSH-CL/liposomes could be a promising drug delivery system for PD treatment. Keywords: Parkinson’s disease, liposomes, phosphatidic acid, targeted-therapy, blood-brain barrier