Lincopan Nilton, Mamizuka Elsa M, Carmona-Ribeiro Ana M
Departamento de Análises Clínicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Brazil.
J Antimicrob Chemother. 2003 Sep;52(3):412-8. doi: 10.1093/jac/dkg383. Epub 2003 Aug 13.
Solubilization of amphotericin B (AMB) by dioctadecyldimethylammonium bromide (DODAB) bilayer fragments inspired this evaluation of its in vivo activity from survival and tissue burden experiments against systemic candidiasis in a mouse model. AMB (< or =0.1 g/L) was simply added to a DODAB powder dispersion in water (10 g/L) previously prepared by sonication in the absence of organic solvents. The AMB aggregation state was evaluated from UV-visible light absorption and dynamic light scattering for aggregate sizing. AMB was stabilized by the DODAB bilayer fragments in its monomeric form, mixing of AMB and DODAB dispersion in pure water causing disappearance of large water-insoluble drug aggregates. From survival experiments, both the bilayer, DODAB/AMB, and the traditional deoxycholate/AMB formulation (DOC/AMB) had identical effect when given by the same route at the same dose of 0.4 mg/kg/day given intraperitoneally for 10 days. From spleen and kidneys tissue burden experiments, similar efficacy of both preparations in reducing tissue cfu counts was obtained. In summary, DODAB/AMB was as effective as DOC/AMB for treating systemic candidiasis in a mouse model.
二辛基二甲基溴化铵（DODAB）双层片段对两性霉素B（AMB）的增溶作用激发了通过生存和组织负荷实验对其在小鼠模型中抗系统性念珠菌病体内活性的评估。将AMB（≤0.1 g/L）简单添加到预先在无有机溶剂条件下通过超声处理制备的水中DODAB粉末分散液（10 g/L）中。通过紫外-可见光吸收和动态光散射对聚集体大小进行评估，以确定AMB的聚集状态。AMB以单体形式被DODAB双层片段稳定，在纯水中将AMB和DODAB分散液混合会导致大的水不溶性药物聚集体消失。从生存实验来看，双层制剂DODAB/AMB和传统的脱氧胆酸盐/AMB制剂（DOC/AMB）在以相同剂量0.4 mg/kg/天腹腔注射给药10天时，通过相同途径给药具有相同效果。从脾脏和肾脏组织负荷实验可知，两种制剂在降低组织菌落形成单位计数方面具有相似的疗效。总之，在小鼠模型中，DODAB/AMB治疗系统性念珠菌病的效果与DOC/AMB一样好。
