Chono Sumio
Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, Otaru City, Japan.
Yakugaku Zasshi. 2007 Sep;127(9):1419-30. doi: 10.1248/yakushi.127.1419.
Drug delivery systems (DDS) using liposomes as drug carriers for targeting to macrophages have been developed for the treatment of diseases that macrophages are related to their progress. Initially, DDS for the treatment of atherosclerosis are described. The influence of particle size on the drug delivery to atherosclerotic lesions that macrophages are richly present and antiatherosclerotic effects following intravenous administration of liposomes containing dexamethasone (DXM-liposomes) was investigated in atherogenic mice. Both the drug delivery efficacy of DXM-liposomes (particle size, 200 nm) to atherosclerotic lesions and their antiatherosclerotic effects were greater than those of 70 and 500 nm. These results indicate that there is an optimal particle size for drug delivery to atherosclerotic lesions. DDS for the treatment of respiratory infections are then described. The influence of particle size and surface mannosylation on the drug delivery to alveolar macrophages (AMs) and antibacterial effects following pulmonary administration of liposomes containing ciprofloxacin (CPFX-liposomes) was investigated in rats. The drug delivery efficacy of CPFX-liposomes to AMs was particle size-dependent over the range 100-1000 nm and then became constant at over 1000 nm. These results indicate that the most effective size is 1000 nm. Both the drug delivery efficacy of mannosylated CPFX-liposomes (particle size, 1000 nm) to AMs and their antibacterial effects were significantly greater than those of unmodified CPFX-liposomes. These results indicate that the surface mannosylation is useful method for drug delivery to AMs. This review provides useful information to help in the development of novel pharmaceutical formulations aimed at drug targeting to macrophages.
已开发出以脂质体作为药物载体靶向巨噬细胞的药物递送系统（DDS），用于治疗与巨噬细胞相关的疾病进展。最初，描述了用于治疗动脉粥样硬化的DDS。在致动脉粥样硬化小鼠中，研究了粒径对富含巨噬细胞的动脉粥样硬化病变的药物递送以及静脉注射含地塞米松脂质体（DXM-脂质体）后的抗动脉粥样硬化作用的影响。DXM-脂质体（粒径200 nm）对动脉粥样硬化病变的药物递送效果及其抗动脉粥样硬化作用均大于70 nm和500 nm的脂质体。这些结果表明，存在向动脉粥样硬化病变进行药物递送的最佳粒径。接着描述了用于治疗呼吸道感染的DDS。在大鼠中，研究了粒径和表面甘露糖基化对含环丙沙星脂质体（CPFX-脂质体）肺部给药后向肺泡巨噬细胞（AMs）的药物递送及抗菌作用的影响。CPFX-脂质体向AMs的药物递送效果在100 - 1000 nm范围内依赖于粒径，在超过1000 nm时变得恒定。这些结果表明最有效的粒径为1000 nm。甘露糖基化CPFX-脂质体（粒径1000 nm）向AMs的药物递送效果及其抗菌作用均显著大于未修饰的CPFX-脂质体。这些结果表明表面甘露糖基化是向AMs进行药物递送的有用方法。本综述提供了有用信息，有助于开发旨在靶向巨噬细胞的新型药物制剂。
