期刊
BIOMATERIALS
卷 30, 期 8, 页码 1613-1626出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2008.12.006
关键词
Cell viability; Brain; Controlled drug release; Copolymers
资金
- Comision Interministerial de Ciencia y Tecnologia, CICYT [MAT2007-63355]
- CSIC [PIF: 200580F0061-62-63]
- NoE EXPERTISSUES [5002832]
- Spanish Ministry of Science and Education [FPU AP2005-0246]
Polymeric drugs carrying glycolipids have been designed as target macromolecules for the treatment of brain tumours. A methacrylate derivative of oleyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside (OAGMA) has been prepared and the corresponding glycopolymer obtained by free radical polymerisation. To modulate the hydrophobic character of the polymeric drug, the acrylic glycomonomner was copolymerised with vinyl pyrrolidone (VP). Reactivity ratios obtained by performing copolymerisation reactions inside the NMR apparatus were r(OAGMA) = 5.94 and r(VP) = 0.01, indicating the Much higher reactivity of the glycomonomer. The hydrolytical release of oleyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside (OAG) from the copolymeric drugs was produced in vitro by the ester enzymatic hydrolysis Using enzyme/buffered Solutions. The cytotoxicity of OAG and OAGMA tested against a human glioblastoma line and normal fibroblasts revealed a concentration dependent selectivity towards tumour cells versus fibroblasts. The antimitotic activity of the copolymeric drugs was also confirmed. The addition Of the eluates of the copolymeric systems collected at 1 and 2 days produced a significant decrease in cellular viability of the glioblastoma cells without affecting that of normal fibroblasts. Oil the contrary, fibroblasts were able to adhere and proliferate onto the copolymeric systems showing normal morphology and revealing a good biocompatibility of the copolymeric drugs against healthy cells. (C) 2008 Elsevier Ltd. All rights reserved.
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