Department of Pharmaceutical Technology, Friedrich Schiller University Jena, Lessingstrasse 8, 07743 Jena, Germany.
J Photochem Photobiol B. 2010 Dec 2;101(3):238-50. doi: 10.1016/j.jphotobiol.2010.07.009. Epub 2010 Jul 27.
In the case of cutaneous malignant or non-malignant diseases, topical photodynamic therapy (PDT) with a temoporfin (mTHPC)-containing formulation would be advantageous. Unfortunately, mTHPC is a highly hydrophobic drug with low percutaneous absorption and novel mTHPC-loaded invasomes for enhanced skin delivery were developed. The purpose of this study was to investigate photodynamic efficacy of mTHPC-loaded invasomes in vitro in two cell lines, i.e. the human colorectal tumour cell line HT29 and the epidermoid tumour cell line A431. Invasomes are vesicles containing besides phospholipids a mixture of terpenes or only one terpene and ethanol. Dark toxicity, phototoxicity and intracellular localization of mTHPC were studied. Laser scanning microscopy indicated perinuclear localization of mTHPC. Results revealed that mTHPC-invasomes and mTHPC-ethanolic solution used at a 2μM mTHPC-concentration and photoirradiation at 20J/cm(2) were able to reduce survival of HT29 cells and especially of A431 cells, being more sensitive to PDT. In contrast to HT29 cells, where there was not a significant difference between cytotoxicity of mTHPC-ethanolic solution and mTHPC-invasomes, in A431 cells mTHPC-invasomes were more cytotoxic. Survival of about 16% of A431 cells treated with mTHPC-invasomes is very promising, since it demonstrates invasomes' potential to be used in topical PDT of cutaneous malignant diseases.
在皮肤恶性或非恶性疾病的情况下，使用含有卟啉（mTHPC）的配方进行局部光动力疗法（PDT）将是有利的。不幸的是，mTHPC 是一种具有低经皮吸收的高度疏水性药物，因此开发了新型的载 mTHPC 入侵体以增强皮肤传递。本研究的目的是研究两种细胞系（即人结肠直肠肿瘤细胞系 HT29 和表皮肿瘤细胞系 A431）中载 mTHPC 的入侵体的体外光动力功效。入侵体是包含磷脂和萜类混合物或仅一种萜类和乙醇的囊泡。研究了 mTHPC 入侵体的暗毒性、光毒性和细胞内定位。激光扫描显微镜显示 mTHPC 位于核周。结果表明，在 2μM mTHPC 浓度下使用 mTHPC-入侵体和 mTHPC-乙醇溶液，并在 20J/cm(2)下进行光照射，能够降低 HT29 细胞尤其是 A431 细胞的存活率，对 PDT 更为敏感。与 HT29 细胞不同，mTHPC-乙醇溶液和 mTHPC-入侵体的细胞毒性之间没有显著差异，而在 A431 细胞中，mTHPC-入侵体的细胞毒性更强。用 mTHPC-入侵体处理的 A431 细胞的存活率约为 16%，这非常有前途，因为它证明了入侵体有可能用于皮肤恶性疾病的局部 PDT。
