Institut Galien Paris-Saclay, UMR CNRS 8612, Faculty of Pharmacy, Univ. Paris-Saclay, Bâtiment Henri MOISSAN, 17 avenue des Sciences, 91400 Orsay, France.
BioCIS, UMR CNRS 8076, Faculty of Pharmacy, Univ. Paris-Saclay, Bâtiment Henri MOISSAN, 17 avenue des Sciences, 91400 Orsay, France.
Int J Pharm. 2022 Aug 25;624:121985. doi: 10.1016/j.ijpharm.2022.121985. Epub 2022 Jul 9.
Amphotericin B (AmB) is an effective drug to treat visceral leishmaniasis but its use is limited by its poor oral bioavailability. This article describes the in-vivo evaluation of AmB-loaded, lipid-based cochleate systems designed for the oral route. Two different cochleate formulations were studied: one based on the synthetic phospholipid dioleoylphosphatidylserine (DOPS) and another optimized formulation based on a naturally occurring phosphatidylserine (Lipoid PSP70) that would render the formulation more affordable in developing countries. Their antiparasitic activity was evaluated in a mouse model of visceral leishmaniasis. Limited efficacy was observed for the DOPS-based cochleates after three doses of AmB at 1 mg/kg. The Lipoid PSP70-based cochleates were administered either as a buffered suspension or in enteric-coated capsules. AmB-loaded cochleates administered as a suspension at a high dose (3 × 20 mg/kg) exhibited significant antiparasitic activity while AmB-loaded cochleates in enteric-coated capsules at a lower dose (3 × 5 mg/kg) presented a slightly higher significant activity. A pharmacokinetic and biodistribution study in rats was performed with the Lipoid PSP70-based cochleates, with a single oral dose of 7.5 mg AmB/kg. Cochleates in both administration forms led to lower concentrations of Amphotericin B in the plasma than intravenous AmBisome®. However, more accumulation in the organs of interest (liver, spleen) was observed for both presentations of cochleates than for AmBisome® by the oral route. Therefore, cochleate formulations of AmB that could be produced at a cost accessible for developing countries show promise for the treatment of visceral leishmaniasis.
两性霉素 B（AmB）是治疗内脏利什曼病的有效药物，但由于其口服生物利用度差，其应用受到限制。本文描述了用于口服途径的两性霉素 B 载脂质体泡囊系统的体内评价。研究了两种不同的脂质体泡囊制剂：一种基于合成磷脂二油酰磷脂酰丝氨酸（DOPS），另一种基于天然存在的磷脂酰丝氨酸（Lipoid PSP70）的优化制剂，这将使制剂在发展中国家更具成本效益。在一种内脏利什曼病的小鼠模型中评估了它们的抗寄生虫活性。在用 1mg/kg 的两性霉素 B 进行三剂治疗后，基于 DOPS 的脂质体泡囊的疗效有限。Lipoid PSP70 基脂质体泡囊可以制成缓冲混悬液或肠溶胶囊。以高剂量（3×20mg/kg）作为混悬液给予两性霉素 B 载脂质体泡囊显示出显著的抗寄生虫活性，而以较低剂量（3×5mg/kg）给予肠溶胶囊的两性霉素 B 载脂质体泡囊则表现出稍高的显著活性。在大鼠中进行了 Lipoid PSP70 基脂质体泡囊的药代动力学和生物分布研究，单次口服 7.5mg/kg 的两性霉素 B。与静脉内两性霉素 B 脂质体 AmBisome®相比，这两种制剂形式的脂质体泡囊都导致血浆中两性霉素 B 的浓度降低。然而，与 AmBisome®相比，两种制剂形式的脂质体泡囊在感兴趣的器官（肝、脾）中的积累更多。因此，对于发展中国家来说，两性霉素 B 的脂质体泡囊制剂具有治疗内脏利什曼病的潜力。
