组氨酸-聚乙二醇-灵芝多糖-甲氨喋呤纳米粒子的制备及表征
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摘要
将L-组氨酸(His)和聚乙二醇(PEG)通过化学键连接得到L-组氨酸-聚乙二醇化合物,再将L-组氨酸-聚乙二醇和疏水药物甲氨蝶呤(MTX)分别与灵芝多糖(GLP)化学连接,制备得到组氨酸-聚乙二醇-灵芝多糖-甲氨喋呤结合物,然后该结合物在水中自组装制备L-组氨酸-聚乙二醇-灵芝多糖-甲氨蝶呤纳米粒子。采用红外光谱(FT-IR)和核磁共振(NMR)对L-组氨酸-聚乙二醇-灵芝多糖-甲氨蝶呤结合物进行了结构表征;通过透射电镜(TEM)对纳米粒子的形貌和粒径进行了表征。1 HNMR结果表明His通过羧基与PEG的氨基连接,His-PEG结合物和甲氨蝶呤通过羧基与灵芝多糖的羟基连接;FT-IR测试结果进一步验证了上述结构;TEM观测到His-PEG-GLP-MTX纳米粒子呈球形,粒径均一,约为300nm。
L-histidine(His)was linked to polyethylene glycol(PEG),and then histidine-polyethylene glycolganoderma lucidum polysaccharide-methotrexate conjugates were synthesized by indroducing L-histidine-polyethylene glycol conjugate and hydrophobic drug methotrexate(MTX)into ganoderma lucidum polysaccharide(GLP),then the conjugates was self-assembled into histidine-polyethylene glycol-ganoderma lucidum polysaccharide-methotrexate conjugte(His-PEG-GLP-MTX)nanoparticles in the water,it can be used to drug nanocarriers.The HisPEG-GLP-MTX conjugates were characterized by infrared(FT-IR)spectra and nuclear magnetic resonance(NMR).The morphology and particle size of the nanoparticles were observed by transmission electron microscopy(TEM).The results of ~1HNMR showed that His was connected with PEG amino group via carboxyl group,HisPEG conjugate and methotrexate were successful connected with hydroxy group of ganoderma lucidum polysaccharide via carboxyl group;the above structure was further verified by FT-IR test;The His-PEG-GLP-MTX nanoparticles are spherical and have a uniform particle size of about 300 nm.
L-histidine(His)was linked to polyethylene glycol(PEG),and then histidine-polyethylene glycolganoderma lucidum polysaccharide-methotrexate conjugates were synthesized by indroducing L-histidine-polyethylene glycol conjugate and hydrophobic drug methotrexate(MTX)into ganoderma lucidum polysaccharide(GLP),then the conjugates was self-assembled into histidine-polyethylene glycol-ganoderma lucidum polysaccharide-methotrexate conjugte(His-PEG-GLP-MTX)nanoparticles in the water,it can be used to drug nanocarriers.The HisPEG-GLP-MTX conjugates were characterized by infrared(FT-IR)spectra and nuclear magnetic resonance(NMR).The morphology and particle size of the nanoparticles were observed by transmission electron microscopy(TEM).The results of ~1HNMR showed that His was connected with PEG amino group via carboxyl group,HisPEG conjugate and methotrexate were successful connected with hydroxy group of ganoderma lucidum polysaccharide via carboxyl group;the above structure was further verified by FT-IR test;The His-PEG-GLP-MTX nanoparticles are spherical and have a uniform particle size of about 300 nm.
引文
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[3]颜美秋.以两亲膦腈为载体的阿霉素的制备及体外评价[D].杭州:浙江大学.
[4]Zi-Yi Zhou,Yu-Ping Tang,Jun Xiang,et al.Neuroprotective effects of water-soluble ganoderma lucidum polysaccharides on cerebral ischemic injury in rats[J].Journal of Ethnopharmacology,2010,131(1):154.
[5]陈丽华,肖新宇,曾惠瑯,等.灵芝多糖对甲氨蝶呤诱导的小鼠肠道损伤的保护作用[J].中国临床药理学与治疗学,2009,14(10):1110-1114.
[6]陈琳琳,韩文涛,何静.纤维素接枝聚甲基丙烯酸甲酯的制备及其药物缓释性能研究[J].精细与专用化学品,2016,24(3):28-32.
[7]周鸿立,杨晓红,李春华,等.玉米须多糖sevag法脱蛋白的方法研究[J].安徽农业科学,2010,38(28):15517-15518,15521.
[8]Lingling Wang,Longfei Wang,Qingshan Shi,et al.Purification and molecular weight distribution of a key exopolysaccharide component of Bacillus megaterium TF10[J].Journal of Environmental Sciences,2016,63(1):9-5.
[9]Shenghua Zha,Qingsheng Zhao,Jinjin Chen,et al.Extraction,purification and antioxidant activities of the polysaccharides from maca(Lepidium meyenii)[J].Carbohydrate Polymers,2014,11(1):24.
[10]夏泉,刘钢,葛朝亮,等.Sevag法去除黄芪粗多糖中蛋白质成分的研究[J].安徽医药,2007(12):1069-1071.
[11]Andreas Wicki,Dominik Witzigmann,Vimalkumar Balasubramanian,et al.Nanomedicine in cancer therapy:Challenges,opportunities,and clinical applications[J].Journal of Controlled Release,2015,200:138.
[12]林志彬.灵芝抗肿瘤作用的免疫学机制及其临床应用[J].中国药理学与毒理学杂志,2015,29(06):865-882.