De Logu A, Fadda A M, Pellerano M L, Diana G, Schivo M L
Sezione di Microbiologia e Virologia, Dipartimento di Scienze Chirurgiche e Trapianti d'Organo, Universit¿a di Cagliari, Via Palabanda 14, 09123, Cagliari, Italy.
Int J Antimicrob Agents. 2000 Jun;15(1):43-8. doi: 10.1016/s0924-8579(00)00124-2.
The antifungal activity of the imidazole derivatives miconazole and ketoconazole was reduced when they were entrapped in liposomal structures and significant differences were detected between small unilamellar vesicles (SUV) and multilamellar vesicles (MLV). To understand which component of liposomes interfered with the antifungal activity of miconazole and ketoconazole, we examined the influence of pure egg and soy L-alpha-phosphatidylcholine and cholesterol on activity against Candida albicans ATCC E10231 by time killing curves. Association of phospholipids-cholesterol-imidazole leads to an inhibitory effect on the antifungal activity comparable to that shown when miconazole or ketoconazole were entrapped in SUV liposomes or when miconazole and ketoconazole were incubated in the presence of L-alpha-phosphatidylcholine. The antifungal activity determined in the presence of cholesterol was comparable to that observed with the free drugs. Inhibition of the antifungal activity of miconazole and ketoconazole by phospholipids is dependent on the phospholipid concentration but is independent of the source of phospholipids (egg or soy). Cholesterol had no influence on the antifungal activity of the imidazoles, unlike the effect on other antifungal drugs, such as amphotericin B.
当咪唑衍生物咪康唑和酮康唑包裹于脂质体结构中时，其抗真菌活性降低，且在小单层脂质体（SUV）和多层脂质体（MLV）之间检测到显著差异。为了解脂质体的哪个成分干扰了咪康唑和酮康唑的抗真菌活性，我们通过时间杀菌曲线研究了纯鸡蛋和大豆L-α-磷脂酰胆碱以及胆固醇对白色念珠菌ATCC E10231活性的影响。磷脂-胆固醇-咪唑的结合对抗真菌活性产生抑制作用，这与咪康唑或酮康唑包裹于SUV脂质体中或咪康唑和酮康唑在L-α-磷脂酰胆碱存在下孵育时所显示的抑制作用相当。在胆固醇存在下测定的抗真菌活性与游离药物观察到的活性相当。磷脂对咪康唑和酮康唑抗真菌活性的抑制作用取决于磷脂浓度，但与磷脂来源（鸡蛋或大豆）无关。与对其他抗真菌药物（如两性霉素B）的作用不同，胆固醇对咪唑类抗真菌活性没有影响。
