Physicochemical Characterization of Molecular Assemblies of Miltefosine and Amphotericin B

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• 作者：C&eacute ; cile M&eacute ; nez ; Philippe Legrand ; V&eacute ; ronique Rosilio ; Sylviane Lesieur ; Gillian Barratt
• 刊名：Molecular Pharmaceutics
• 出版年：2007
• 出版时间：April 2007
• 年：2007
• 卷：4
• 期：2
• 页码：281 - 288
• 全文大小：167K
• 年卷期：v.4,no.2(April 2007)
• ISSN：1543-8392

文摘

This study describes the interactions between two amphiphilic molecules withantileishmanial activity, amphotericin B (AmB) and miltefosine [hexadecylphosphocholine(HePC)], the latter being effective by the oral route. The effect of HePC on the aggregationstate of AmB in aqueous solution and the interactions between the two agents were monitoredusing absorption spectroscopy and circular dichroism. Structural characterization of the mixedaggregates formed in water by dynamic light scattering (DLS) and cryofracture electronmicroscopy was performed. At concentrations above its critical micelle concentration, HePCwas shown to interact with AmB, leading to an increase in the proportion of AmB in its monomericform as a result of a micellar solubilization mechanism with a capacity of 26 ± 3 mmol of AmBsolubilized/mol of HePC, that is, nearly 40 molecules of HePC per molecule of AmB in the mixedmicelles. These were revealed as individual and spherical aggregates close to 10 nm in diameterby both electron microscopy and DLS. Such a micellar formulation provides a new AmB-basedsystem which might be useful in delivering AmB orally for visceral leishmaniasis bitherapy.