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光谱研究抗癌药物米托蒽醌与非离子表面活性剂胶束的分子相互作用。

Spectroscopic investigations of the molecular interaction of anticancer drug mitoxantrone with non-ionic surfactant micelles.

机构信息

Institute of Physical Chemistry I. Murgulescu, Romanian Academy, University of Bucharest, Bucharest, Romania.

出版信息

J Pharm Pharmacol. 2012 May;64(5):688-96. doi: 10.1111/j.2042-7158.2012.01445.x. Epub 2012 Feb 7.

Abstract

OBJECTIVES

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.

METHODS

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.

KEY FINDINGS

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.

CONCLUSIONS

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.

摘要

目的

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。

方法

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。

主要发现

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。

结论

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。

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