一种对pH敏感的地塞米松前药的合成、表征及体外特性研究
Synthesis,characterization and in vitro evaluation of Dexamethasone prodrug with pH sensitive
作者：俞秀恒;李沉纹;吴国菻;付元元;王庆;卢来春;赵语;
Author：
收稿日期： 年卷（期）页码：2016,31(02):-113-116
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：地塞米松;聚N-(2-羟丙基)甲基丙烯酰胺;前药;类风湿关节炎;pH敏感;体外释放
Key words：
基金项目：重庆市卫生局医学科研项目(2012-2-142;2012-2-22);;
重庆市国际合作项目(cstc201110001)
中文摘要
目的合成具有p H敏感特性的聚N-(2-羟丙基)甲基丙烯酰胺(HPMA)负载地塞米松(Dex)的前药。方法以双甘氨肽(Gly-Gly-OH)为连接臂,将Dex与HPMA共价连接,再经聚合反应形成高分子地塞米松前药(P-Dex)。考察其水溶性,通过核磁共振表征其结构,酸水解后HPLC法测定Dex的含量。考察P-Dex在p H5、p H7.4的释药特性。结果合成的P-Dex改善了Dex的水溶性,P-Dex中Dex的含量为4.59%。P-Dex在p H7.4缓冲体系中几乎不释放Dex,在p H5的缓冲体系中,每天约释放0.86%Dex。结论合成的P-Dex增强了Dex的水溶性,具有p H敏感释放的特点。
参考文献
[1]Rang HP,Dale MM,Ritter JM,et al.Rang and Dale's Pharmacology[M].7th edn.Edinburgh:Elsevier Saunders,2012:100.
[2]Urbańska J,Karewicz A,Nowakowska M.Polymeric delivery systems for Dexamethasone[J].Life Sci,2014,96(1):1-6.
[3]Coimbra M,Rijken C J,Stigte RM,et al.Antitumor efficacy of Dexamethasone-loaded core-crosslinked polymeric micelles[J].Control Rel,2012,163:361-367.
[4]Venditti I,Fontana L,Fratoddi I,et al.Direct interaction of hydrophilic gold nanoparticles with Dexamethasone drug:Loading and release study[J].J Colloid Interface Sci,2014,418:52-60.
[5]Kobayashi H,Watanabe R,Choyke PL.Improving conventional enhanced permeability and retention(EPR)effects;what is the appropriate target[J].Theranostics,2013,4(1):81-89.
[6]Andersson SE,Lexmuller K,Johansson A,et al.Tissue and intracellular p H in normal periarticular soft tissue and during different phases of antigen induced arthritis in therat[J].Rheumatol,1999,26:2018-2024.
[7]RˇíhováB,Kopecˇek J,Ulbrich K,et al.Immunogenicity of N-(2-hydroxypropyl)methacryl-amide copolymers[J].Makromol Chem Suppl,1985,9:13-24.
[8]Strohalm M,Strohalm J,Kaftan F,et al.Poly[N-(2-hydroxypropyl)methacryl-amide]-based tissue-embedding medium compatible with MALDI mass spectrometry imaging experiments[J].Analy Chem,2011,83(13):5458-5462.
[9]Gonzalez LI.Synthetic stereoisomer peptides in the retro-inverso and inverso configuration,and with cyclic and linear structure,their polymer conjugates,their encapsulation in polymer particles,and uses thereof[P].US Patent Application 13/732,951.2013,1-2.
[10]Kopcek J,Kopeckova P,Miller S C,et al.Macromolecular delivery systems for non-invasive imaging,evaluation and treatment of arthritis and other inflammatory diseases[P].US Patent Application 10/591,258.2005-3-30.
[11]Wang D,Miller SC,Liu XM,et al.Novel Dexamethasone-HPMA copolymer conjugate and its potential application in treatment of rheumatoid arthritis[J].Arthritis Res Ther 2007,9:R2.
[12]Liu XM,Quan LD,Tian J,et al.Synthesis and evaluation of a well-defined HPMA copolymer-Dexamethasone conjugate for effective treatment of rheumatoid arthritis[J].Pharma Res,2008,25(12):2910-2919.
[13]Lai JT,Filla D,Shea R.Functional polymers from novel carboxyl-terminated trithiocarbonates as highly efficient RAFT agents[J].Macromolecules,2002,35(18):6754-6756.
【关闭】
