Prodrugs of 5-aminolevulinic acid for photodynamic therapy
Prodrugs of 5-aminolevulinic acid for photodynamic therapy
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DOI：
10.1111/j.1751-1097.1996.tb01868.x
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发表时间：
1996-12-01
影响因子：
3.3
通讯作者：
vanHenegouwen, GMJB
中科院分区：
文献类型：
--
作者：
Kloek, J;vanHenegouwen, GMJB
5-氨基酮丙酸(ALA)作为原卟啉IX(PPIX)前体用于光动力疗法(PDT)在短时间内变得非常流行，然而，尽管ALA具有优点，但也有缺点：由于其亲脂性较低，其通过生物膜的扩散能力较差。因此，必须给予大剂量的ALA，以便使受累组织中的PpIX增加到足以进行PDT的水平。这个问题的一个可能的解决方案是使用丙氨酸的衍生物。由于ALA前体药的亲脂性增强，有望具有更好的扩散性能，并在酶解后转化为母体ALA。在本报告中，介绍了一些丙氨酸衍生物的合成结果。在体外细胞测试系统中，对ALA前药的细胞穿透和PpIX形成的最佳条件进行了研究。结果表明，与丙氨酸相比，几种前药确实能显著提高PpIX的积累量。最后，最有希望的前体药物在动物模型中进行了测试，结果显示在这些条件下PpIX的形成也增加了。
The use of 5-aminolevulinic acid (ALA) as a protoporphyrin IX (PpIX) precursor for photodynamic therapy (PDT) became very popular in a short time, However, despite its advantages, ALA also has a drawback; it shows a poor ability to diffuse through biological membranes because of its low lipophilicity. AS a consequence, a high dose of ALA must be administered in order to increase PpIX in the afflicted tissue at a level sufficient for PDT. A possible solution to this problem is the use of derivatives of ALA. ALA prodrugs are expected to have better diffusing properties as a result of their enhanced lipophilicity and are converted into the parent ALA after enzymatic hydrolysis. In this report, results are presented of the synthesis of a number of ALA derivatives. The ALA prodrugs were investigated regarding the optimum conditions for cell penetration and PpIX formation in an in vitro cellular test system. It is shown that several prodrugs do indeed enhance the amount of accumulated PpIX considerably as compared to ALA. Finally, the most promising prodrugs were tested in an animal model and showed increased PpIX formation under these conditions as well.