AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience
AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience
复制标题
DOI：
10.1093/jac/49.suppl_1.21
复制
发表时间：
2002-02-01
影响因子：
5.2
通讯作者：
Proffitt, RT
中科院分区：
文献类型：
--
作者：
Adler-Moore, J;Proffitt, RT
两性霉素B是治疗危及生命的系统性真菌感染（例如念珠菌病和曲霉病）的首选治疗方法。为了提高该药物的疗效并降低其急性和慢性毒性，已经开发了该药物的几种脂质制剂，包括AmBisome，一种阿替霉素B的脂质体制剂。脂质体由高转变温度磷脂和胆固醇组成，旨在将阿替霉素B安全地掺入脂质体双层中。AmBisome可以结合到真菌细胞壁，其中脂质体被破坏。从脂质体中释放后，阿替霉素B被认为通过细胞壁转移并与真菌细胞膜中的麦角固醇结合。AmBisome的这种作用机制导致其有效的体外杀真菌活性，同时在哺乳动物细胞存在下保持脂质体的完整性，其具有最小的毒性。在动物模型中，AmBisome可有效治疗细胞内（利什曼病和组织胞浆菌病）和细胞外（念珠菌病和曲霉病）全身性感染。由于其在器官水平的低毒性，静脉内AmBisome可以以显著高剂量的阿替霉素B（1-30 mg/kg）安全地递送，用于治疗全身性真菌感染。AmBisome在动物中具有5-24小时的循环半衰期，并且在动物模型中似乎定位于脑（隐球菌病、曲霉病、球孢子菌病）、肺（芽生菌病、副球孢子菌病、曲霉病）和肾（念珠菌病）中的感染部位，递送在治疗后数周内在组织中保持生物可利用性的曲霉素B。
Amphotericin B is the treatment of choice for life-threatening systemic fungal infections such as candidosis and aspergillosis. To improve this drug's efficacy and reduce its acute and chronic toxicities, several lipid formulations of the drug have been developed, including AmBisome, a liposomal formulation of amphotericin B. The liposome is composed of high transition temperature phospholipids and cholesterol, designed to incorporate amphotericin B securely into the liposomal bilayer. AmBisome can bind to fungal cell walls, where the liposome is disrupted. The amphotericin B, after being released from the liposomes, is thought to transfer through the cell wall and bind to ergosterol in the fungal cell membrane. This mechanism of action of AmBisome results in its potent in vitro fungicidal activity while the integrity of the liposome is maintained in the presence of mammalian cells, for which it has minimal toxicity. In animal models, AmBisome is effective in treating both intracellular (leishmaniasis and histoplasmosis) and extracellular (candidosis and aspergillosis) systemic infections. Because of its low toxicity at the organ level, intravenous AmBisome can be safely delivered at markedly high doses of amphotericin B (1-30 mg/kg) for the treatment of systemic fungal infections. AmBisome has a circulating half-life of 5-24 h in animals, and in animal models appears to localize at sites of infection in the brain (cryptococcosis, aspergillosis, coccidioidomycosis), lungs (blastomycosis, paracoccidioidomycosis, aspergillosis) and kidneys (candidosis), delivering amphotericin B that remains bioavailable in tissues for several weeks following treatment.