Evaluation of Phenylbutazone and Poly(amidoamine) Dendrimers Interactions by a Combination of Solubility, 2D-NOESY NMR, and Isothermal Titration Calorimetry Studies

被引：51
作者：
Yang, Wenjun [1 ,2 ]
Li, Yiwen [3 ]
Cheng, Yiyun [1 ,2 ,3 ]
Wu, Qinglin [1 ,2 ]
Wen, Longping [1 ,2 ]
Xu, Tongwen [3 ]
机构：
[1] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China
[2] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China
[3] Univ Sci & Technol China, Dept Chem, Lab Funct Membranes, Hefei 230026, Anhui, Peoples R China
来源：
JOURNAL OF PHARMACEUTICAL SCIENCES | 2009年 / 98卷 / 03期
关键词：
poly(amidoamine); PAMAM; dendrimer; phenylbutazone; solubilization; 2D-NOESY; ITC; interaction; encapsulation; electrostatic attachment; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BETA-CYCLODEXTRIN; AQUEOUS SOLUBILITY; IN-VITRO; COMPLEXATION; DELIVERY; CARRIERS; MICROCALORIMETRY; SURFACE;
D O I：
10.1002/jps.21519
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The interactions between phenylbutazone, a well-established nonsteroidal anti-inflammatory drug, with different generations of poly(amidoamine) (PAMAM) dendrimers, have been investigated by aqueous solubility, two dimensional nuclear Overhauser effect spectroscopy (2D-NOESY) and isothermal titration calorimetry (ITC) studies. Solubility results showed that PAMAM dendrimers significantly enhanced the aqueous solubility of phenylbutazone and the solubilization was much influenced by dendrimer concentration, generation, surface function group and pH value. The 2D-NOESY spectra clearly showed that there were several kinds of cross-peaks from NOE interactions between the protons of phenylbutazone and the protons in interior cavities of both generation 6 and generation 3 PAMAM dendrimers. The solubility, 2D-NOESY results and ITC analysis suggest that encapsulation and electrostatic interaction together caused the solubility enhancement of phenylbutazone. The new techniques such as 2D-NOESY and ITC used in this study are useful tools in investigating the interactions between dendrimers and guest molecules. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1075-1085, 2009
引用
收藏
页码：1075 / 1085
页数：11
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