Institute of Physical Chemistry I. Murgulescu, Romanian Academy, University of Bucharest, Bucharest, Romania.
J Pharm Pharmacol. 2012 May;64(5):688-96. doi: 10.1111/j.2042-7158.2012.01445.x. Epub 2012 Feb 7.
The aim of this study was to investigate the interaction of the anticancer drug mitoxantrone with non-ionic micelles, as simple model systems of biological membranes.
UV-VIS absorption spectroscopy was used to quantify the drug-surfactant micelle interactions in terms of the binding constant and the micelle-water partition coefficient of the drug.
Interaction of mitoxantrone with non-ionic micelles reduces the dimerization process of mitoxantrone, the drug molecules being encapsulated into micelles as monomer. The strength of the interaction between mitoxantrone and non-ionic micelles is higher at pH10 than at pH7.4, and depends on the surfactant in the order Tween 80>Tween 20>Triton X-100. The higher partition coefficient at pH10 compared to pH7.4 suggests that at basic pH the deprotonated mitoxantrone is incorporated more efficiently into the hydrophobic medium of non-ionic micelles compared to physiological pH, when the protonated drug is predominant.
These results on simple model systems miming the drug-membrane interactions contribute to the elucidation of the behaviour of the drug in vivo, as well as the possible utilization of surfactant micelles as drug carriers.
本研究旨在研究抗癌药物米托蒽醌与非离子型胶束的相互作用,这些胶束作为生物膜的简单模型系统。
采用紫外-可见吸收光谱法,根据结合常数和药物的胶束-水分配系数,定量研究药物-表面活性剂胶束的相互作用。
米托蒽醌与非离子型胶束的相互作用降低了米托蒽醌的二聚过程,药物分子作为单体被包裹在胶束中。米托蒽醌与非离子型胶束的相互作用强度在 pH10 时高于 pH7.4,并且取决于表面活性剂的顺序为吐温 80>吐温 20>Triton X-100。与生理 pH 相比,在 pH10 时更高的分配系数表明,在碱性 pH 下,与质子化药物为主时相比,去质子化的米托蒽醌更有效地掺入非离子型胶束的疏水环境中。
这些模拟药物-膜相互作用的简单模型系统的结果有助于阐明药物在体内的行为,以及表面活性剂胶束作为药物载体的可能利用。