The Effective Solubilization of Hydrophobic Drugs Using Epigallocatechin Gallate or Tannic Acid-Based Formulations
The Effective Solubilization of Hydrophobic Drugs Using Epigallocatechin Gallate or Tannic Acid-Based Formulations
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DOI：
10.1016/j.xphs.2016.06.027
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发表时间：
2016-10-01
影响因子：
3.8
通讯作者：
Letchford, Kevin
中科院分区：
文献类型：
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作者：
Jackson, John K.;Letchford, Kevin
疏水药物的水溶增溶需要超摩尔量的水溶助长剂，具有潜在的毒性问题。我们研究了使用表没食子儿茶素没食子酸酯（EGCG）和单宁酸在毫摩尔浓度，作为水溶助长剂样增溶剂。将紫杉醇、多西他赛、阿齐霉素B、姜黄素或雷帕霉素用EGCG或单宁酸从乙醇中干燥，然后再溶解于水性介质中。离心和过滤后，使用HPLC测量药物溶解度。使用放射性标记药物测量多西他赛从基于EGCG的溶液中摄取到细胞中。在毫摩尔浓度下，EGCG和鞣酸均以浓度依赖性方式有效地将所有药物的水溶性从低水平（μ g/mL）增加到高水平（mg/mL）。溶液通常在室温下稳定超过24小时。与胶束制剂相比，基于EGCG的多西他赛溶液在所有细胞系中表现出显著改善的药物摄取或转运水平。这些添加剂的使用可提供使用口服、肠胃外、局部或装置相关递送系统的各种疏水性药物的改进制剂。(C)2016年美国药学协会（R）。爱思唯尔公司出版All rights reserved.
Hydrotropic solubilization of hydrophobic drugs requires supramolar amounts of hydrotropes with potential toxicity issues. We investigated the use of epigallocatechin gallate (EGCG) and tannic acid at millimolar concentrations, as hydrotrope-like solubilizing agents. Paclitaxel, docetaxel, amphotherecin B, curcumin, or rapamycin were dried down with EGCG or tannic acid from ethanol and then redissolved in aqueous media. Following centrifugation and filtration, the drug solubility was measured using HPLC. The uptake of docetaxel into cells from EGCG-based solutions was measured using radiolabeled drugs. Both EGCG and tannic acid effectively increased the aqueous solubility of all drugs from low levels (mu g/mL) to high levels (mg/mL) in a concentration-dependent fashion at millimolar concentrations. Solutions were generally stable at room temperature over 24 h. Compared with micellar formulations, EGCG-based solutions of docetaxel demonstrated markedly improved drug uptake or transport levels in all cell lines. The use of these additives may provide improved formulation of various hydrophobic drugs using oral, parenteral, localized, or device-associated delivery systems. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.