Barioni Marina Berardi, Ramos Ana Paula, Zaniquelli Maria Elisabete Darbello, Acuña Alberto Ulises, Ito Amando Siuiti
Departamento de Física, FFCLRP, Universidade de São Paulo, Bandeirantes Avenue 3900, 14040-901 Ribeirão Preto, São Paulo, Brazil.
Departamento de Química, FFCLRP, Universidade de São Paulo, Bandeirantes Avenue 3900, 14040-901 Ribeirão Preto, São Paulo, Brazil.
Biophys Chem. 2015 Jan;196:92-9. doi: 10.1016/j.bpc.2014.10.002. Epub 2014 Oct 16.
Miltefosine (hexadecylphosphocholine, MT) afforded successful oral treatment against human visceral and cutaneous leishmaniasis. Knowledge of MT aggregation in aqueous solutions and of its interaction with lipid membranes is important to understand pharmacokinetics, bioavailability and antiparasitic effects. Methods based on surface tension and fluorescence spectroscopy gave the value of 50μM for critical micelle concentration (CMC) in buffered water solution, and the value is influenced by salt content. Interaction between MT and lipid vesicles was monitored by fluorescence and the drug promotes only minor changes in the surface of the vesicles. At MT concentration below CMC, modifications in probe fluorescence are due to disordering effects promoted by the drug in the bilayer. Above the CMC, MT promoted large modifications in the vesicles as a whole, resulting in mixed aggregates containing lipids, drug and probe. Effects are less evident above thermal phase transition when the bilayer is in less ordered state.
米替福新（十六烷基磷酸胆碱，MT）为人类内脏利什曼病和皮肤利什曼病提供了成功的口服治疗方法。了解MT在水溶液中的聚集情况及其与脂质膜的相互作用对于理解其药代动力学、生物利用度和抗寄生虫作用至关重要。基于表面张力和荧光光谱的方法得出，在缓冲水溶液中临界胶束浓度（CMC）的值为50μM，该值受盐含量影响。通过荧光监测MT与脂质囊泡之间的相互作用，药物仅使囊泡表面发生微小变化。在MT浓度低于CMC时，探针荧光的变化是由于药物在双层中促进的无序效应。高于CMC时，MT对整个囊泡产生较大变化，导致形成包含脂质、药物和探针的混合聚集体。当双层处于较无序状态的热相变温度以上时，效应不太明显。
