Synthesis and Characterization of Folate-Mediated Chondroitin Sulfate-g-Poly (ε-Caprolactone)- Doxorubicin Nanoparticles

• Main Authors: Jie-An Ye, 葉婕安
• Other Authors: Li Fang Wang
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/53454270550333139290

碩士 === 高雄醫學大學 === 醫藥暨應用化學研究所 === 100 === In this study, we used double bonds of a hydrophilic chondroitin sulfate methacrylate (CSMA) and a hydrophobic polycaprolactone (PCL) to produce CSMA-g-PCL copolymer (CP) by free radical polymerization. The CP copolymer could be self-assembled into a micelle type. An anticancer agent was linked to the CP to produce CP-Drug. Furthermore, a cancer mediated ligand was grafted onto CP-Drug to improve the cellular uptake into tumor cells. The copolymers were analyzed using a Fourier transform infrared (FTIR) and a 1H nuclear magnetic resonance (1H-NMR) spectrophotometer. Using a fluorescence probe technique, we measured fluorescence intensity vs. concentration to calculate a critical micelle concentration (CMC). The hydrodynamic diameters were measured by dynamic light scattering (DLS). From transmission electron microscopic (TEM) images, the morphology of the CP was spherical and that of CP-Drug was disc-like. We investigated the intracellular delivery of the micelles in U-87 MG (U87-malignant glioma cell) cells. The CP copolymer was non cytotoxic in U87 cells at concentrations of 5-1000 μg/mL. With different incubation periods of 24, 48 and 72 hours, the IC50 values were measured and compared among different micellar particles. From confocal laser scanning microscopic (CLSM) images, the released drug from the micelles could enter the cell nucleus. The cellular uptake and distribution of the particles in U87 cells was acquired using a flow cytometer. Get all results together, the amphiphilic CP and its derivatives containing a drug and / or a ligand were successfully prepared and potentially applied as anticancer agents as well as drug carriers.