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新型接枝共聚物,以结冷胶和 N-乙烯基咪唑为前体,携带甜菜碱单元,用于设计药物传递系统。

New Grafted Copolymers Carrying Betaine Units Based on Gellan and N-Vinylimidazole as Precursors for Design of Drug Delivery Systems.

机构信息

"Petru Poni" Institute of Macromolecular Chemistry, Grigore Ghica Voda Alley, No. 41A, 700487 Iasi, Romania.

Department of Natural and Synthetic Polymers, Faculty of Chemical Engienering and Environmental Protection, "Gheorghe Asachi" Technical University of Iasi, Prof. Dr. Docent Dimitrie Mangeron Street, No. 73, 700050 Iasi, Romania.

出版信息

Molecules. 2020 Nov 20;25(22):5451. doi: 10.3390/molecules25225451.

Abstract

New grafted copolymers possessing structural units of 1-vinyl-3-(1-carboxymethyl) imidazolium betaine were obtained by graft copolymerization of -vinylimidazole onto gellan gum followed by the polymer-analogous reactions on grafted polymer with the highest grafting percentage using sodium chloroacetate as the betainization agent. The grafted copolymers were prepared using ammonium persulfate/,,',' tetramethylethylenediamine in a nitrogen atmosphere. The grafting reaction conditions were optimized by changing one of the following reaction parameters: initiator concentration, monomer concentration, polymer concentration, reaction time or temperature, while the other parameters remained constant. The highest grafting yield was obtained under the following reaction conditions: c = 0.08 mol/L, c = 0.8 mol/L, c = 8 g/L, t = 4 h and T = 50 °C. The kinetics of the graft copolymerization of -vinylimidazole onto gellan was discussed and a suitable reaction mechanism was proposed. The evidence of the grafting reaction was confirmed through FTIR spectroscopy, X-ray diffraction, H-NMR spectroscopy and scanning electron microscopy. The grafted copolymer with betaine structure was obtained by a nucleophilic substitution reaction where the betainization agent was sodium chloroacetate. Preliminary results prove the ability of the grafted copolymers to bind amphoteric drugs (cefotaxime) and, therefore, the possibility of developing the new sustained drug release systems.

摘要

通过接枝共聚反应,将 - 乙烯基咪唑接枝到结冷胶上,然后使用氯乙酸钠作为季铵化试剂,对具有最高接枝率的接枝聚合物进行类似聚合物的反应,得到了具有 1-乙烯基-3-(1-羧甲基)咪唑𬭩甜菜碱结构单元的新型接枝共聚物。接枝共聚物是在氮气气氛中使用过硫酸铵//四甲基乙二胺合成的。通过改变以下反应参数之一来优化接枝反应条件:引发剂浓度、单体浓度、聚合物浓度、反应时间或温度,同时保持其他参数不变。在以下反应条件下获得了最高的接枝产率:c = 0.08 mol/L、c = 0.8 mol/L、c = 8 g/L、t = 4 h 和 T = 50°C。讨论了 - 乙烯基咪唑接枝到结冷胶的接枝共聚动力学,并提出了合适的反应机理。通过傅里叶变换红外光谱、X 射线衍射、H-NMR 光谱和扫描电子显微镜证实了接枝反应的证据。通过亲核取代反应得到了具有甜菜碱结构的接枝共聚物,其中季铵化试剂为氯乙酸钠。初步结果证明了接枝共聚物结合两性药物(头孢噻肟)的能力,因此有可能开发新的缓释药物释放系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e66/7699957/5785a0934cbf/molecules-25-05451-g001.jpg

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