Methoxy Poly(ethylene glycol)-Poly(ε-caprolactone) Nanoparticles Grafted with Wheat Germ Agglutinin and Folic Acid for Targeting Delivery of Anti-cancer Drug to Human Glioblastoma Cells

• Main Authors: Yu-Hsuan Chang, 張鈺瑄
• Other Authors: Yung-Chih Kuo
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/60120632932394780573

碩士 === 國立中正大學 === 化學工程研究所 === 101 === A dual-targeting drug carrier methoxy poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles (MPEG-PCL NPs) and surface modified with wheat germ agglutinin (WGA) and folic acid (FA) for enhanced anticancer drug delivery across the blood–brain barrier (BBB) and targeting to U87MG cells. The MPEG-PCL NPs was prepared using emulsion-solvent evaporation techniques in presence of Pluronic F127. Furthermore, the cell co-culture model was established by consisting of human brain-microvascular endothelial cells, human astrocytes and human brain vascular pericytes to investigate various formulations of drug-loaded NPs permeability of the in vitro BBB model and dual-targeting effect for U87MG cells, then observing the cellular uptake of human brain-microvascular endothelial cells and U87MG cells by immunofluorescence. The results indicated that increase in concentration of F127 from 0.25% to 1% made significant decrease in the average diameter and 1% w/v of F127 was considered as optimum for the preparation of nanoparticles, the optimum average diameter was about 150 nm. In addition, copolymers with shorter PCL blocks formed smaller particles size and encapsulated less drug molecules, but released faster. The results of the release showed that the NPs in this study were pH-dependent. Transepithelial electrical resistance (TEER) value of the in vitro BBB model was 310 ± 11.7 Ω × cm2 and the order of transport across the BBB was FWNPs > WNPs > FNPs > NPs, the dual-targeting nanoparticles FWNPs was 1.5- to 2.1-fold higher than non-modified NPs and the result of dual-targeting effect indicated that FWNPs were significantly against U87MG cells after cross the BBB. Finally, the results of immunofluorescence demonstrated that FWNPs increased intracellular in HBMECs and U87MG cells. Therefore, it may be concluded that FWNPs has the potential to be applied as a targeted delivery for anticancer drug in the treatment of brain cancer.