Ménez Cécile, Legrand Philippe, Rosilio Véronique, Lesieur Sylviane, Barratt Gillian
Laboratoire de Physico-chimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Univ Paris-Sud 11, Faculté de Pharmacie, IFR 141, Châtenay-Malabry, France.
Mol Pharm. 2007 Mar-Apr;4(2):281-8. doi: 10.1021/mp0601143.
This study describes the interactions between two amphiphilic molecules with antileishmanial activity, amphotericin B (AmB) and miltefosine [hexadecylphosphocholine (HePC)], the latter being effective by the oral route. The effect of HePC on the aggregation state of AmB in aqueous solution and the interactions between the two agents were monitored using absorption spectroscopy and circular dichroism. Structural characterization of the mixed aggregates formed in water by dynamic light scattering (DLS) and cryofracture electron microscopy was performed. At concentrations above its critical micelle concentration, HePC was shown to interact with AmB, leading to an increase in the proportion of AmB in its monomeric form as a result of a micellar solubilization mechanism with a capacity of 26 +/- 3 mmol of AmB solubilized/mol of HePC, that is, nearly 40 molecules of HePC per molecule of AmB in the mixed micelles. These were revealed as individual and spherical aggregates close to 10 nm in diameter by both electron microscopy and DLS. Such a micellar formulation provides a new AmB-based system which might be useful in delivering AmB orally for visceral leishmaniasis bitherapy.
本研究描述了两种具有抗利什曼原虫活性的两亲性分子，两性霉素B（AmB）和米替福新[十六烷基磷酸胆碱（HePC）]之间的相互作用，后者经口服有效。利用吸收光谱和圆二色性监测了HePC对AmB在水溶液中聚集状态的影响以及这两种药物之间的相互作用。通过动态光散射（DLS）和冷冻断裂电子显微镜对在水中形成的混合聚集体进行了结构表征。在高于其临界胶束浓度的浓度下，HePC被证明与AmB相互作用，由于胶束增溶机制，导致AmB单体形式的比例增加，其增溶能力为每摩尔HePC增溶26±3 mmol的AmB，即混合胶束中每分子AmB约有40个HePC分子。通过电子显微镜和DLS都显示这些是直径接近10 nm的单个球形聚集体。这种胶束制剂提供了一种新的基于AmB的系统，可能有助于口服递送AmB用于内脏利什曼病的联合治疗。
