Santangelo R, Paderu P, Delmas G, Chen Z W, Mannino R, Zarif L, Perlin D S
Public Health Research Institute, New York, NY 10016, USA.
Antimicrob Agents Chemother. 2000 Sep;44(9):2356-60. doi: 10.1128/AAC.44.9.2356-2360.2000.
Amphotericin B (AMB) remains the principal therapeutic choice for deep mycoses. However, its application is limited by toxicity and a route of administration requiring slow intravenous injection. An oral formulation of this drug is desirable to treat acute infections and provide prophylactic therapy for high-risk patients. Cochleates are a novel lipid-based delivery system that have the potential for oral administration of hydrophobic drugs. They are stable phospholipid-cation crystalline structures consisting of a spiral lipid bilayer sheet with no internal aqueous space. Cochleates containing AMB (CAMB) inhibit the growth of Candida albicans, and the in vivo therapeutic efficacy of CAMB administered orally was evaluated in a mouse model of systemic candidiasis. The results indicate that 100% of the mice treated at all CAMB doses, including a low dosage of 0.5 mg/kg of body weight/day, survived the experimental period (16 days). In contrast, 100% mortality was observed with untreated mice by day 12. The fungal tissue burden in kidneys and lungs was assessed in parallel, and a dose-dependent reduction in C. albicans from the kidneys was observed, with a maximum 3.5-log reduction in total cell counts at 2.5 mg/kg/day. However, complete clearance of the organism from the lungs, resulting in more than a 4-log reduction, was observed at the same dose. These results were comparable to a deoxycholate AMB formulation administered intraperitoneally at 2 mg/kg/day (P < 0.05). Overall, these data demonstrate that cochleates are an effective oral delivery system for AMB in a model of systemic candidiasis.
两性霉素B（AMB）仍然是深部真菌病的主要治疗选择。然而，其应用受到毒性以及需要缓慢静脉注射的给药途径的限制。这种药物的口服制剂对于治疗急性感染以及为高危患者提供预防性治疗是很有必要的。耳蜗形脂质体是一种新型的基于脂质的给药系统，具有口服疏水性药物的潜力。它们是稳定的磷脂 - 阳离子晶体结构，由没有内部水空间的螺旋脂质双层片组成。含两性霉素B的耳蜗形脂质体（CAMB）可抑制白色念珠菌的生长，并在系统性念珠菌病小鼠模型中评估了口服CAMB的体内治疗效果。结果表明，所有CAMB剂量组的小鼠，包括低剂量0.5 mg/kg体重/天，100%在实验期（16天）内存活。相比之下，未治疗的小鼠在第12天时观察到100%死亡。同时评估了肾脏和肺部的真菌组织负荷，观察到肾脏中白色念珠菌数量呈剂量依赖性减少，在2.5 mg/kg/天时总细胞数最多减少3.5个对数级。然而，在相同剂量下观察到肺部真菌完全清除，导致减少超过4个对数级。这些结果与每天腹腔注射2 mg/kg的脱氧胆酸盐AMB制剂相当（P < 0.05）。总体而言，这些数据表明在系统性念珠菌病模型中，耳蜗形脂质体是AMB有效的口服给药系统。
