Bakker-Woudenberg I A, Storm G, Woodle M C
Dept. Clinical Microbiology, Erasmus University Rotterdam, The Netherlands.
J Drug Target. 1994;2(5):363-71. doi: 10.3109/10611869408996811.
The use of liposomes in the treatment of severe infections is under investigation. Classical liposomes which localize in cells of the mononuclear phagocyte system (MPS) can be exploited in two ways. First for targeting of macrophage modulators such as muramyl peptides or IFN-gamma, to stimulate the cells of the MPS to maximal blood clearance capacity. This enhanced nonspecific anti-infectious resistance is important as in immunocompromised patients micro-organisms frequently appear in the blood from a local infection. Secondly, classical liposomes are successfully used as carriers of antibiotics in experimental intracellular parasitic-, viral-, fungal- or bacterial infections in MPS tissues. Based on these data extensive studies in patients with severe fungal infections have demonstrated successful treatment with liposomal or lipid-complexed amphotericin B. More recently, liposomal amphotericin B appeared to be effective in patients with drug-resistant visceral leishmaniasis. For the treatment of Mycobacterium avium complex infection in AIDS patients the efficacy of liposomal gentamicin is under investigation. With respect to infections in non-MPS tissues the applicability of Stealth liposomes characterized by long circulation half-lives is under investigation. Substantial localization of these liposomes in infected lung tissue of rats was demonstrated. Preliminary data in experimental bacterial lung infection showed superior efficacy of antibiotic encapsulated in Stealth liposomes.
脂质体在严重感染治疗中的应用正在研究中。定位于单核吞噬细胞系统(MPS)细胞的传统脂质体可通过两种方式加以利用。其一,用于靶向巨噬细胞调节剂,如胞壁酰肽或干扰素-γ,以刺激MPS细胞达到最大的血液清除能力。这种增强的非特异性抗感染抵抗力很重要,因为在免疫受损患者中,微生物常常从局部感染进入血液。其二,在MPS组织的实验性细胞内寄生虫、病毒、真菌或细菌感染中,传统脂质体成功用作抗生素的载体。基于这些数据,对严重真菌感染患者进行的广泛研究已证明,脂质体或脂质复合两性霉素B治疗成功。最近,脂质体两性霉素B在耐药内脏利什曼病患者中似乎有效。对于艾滋病患者鸟分枝杆菌复合感染的治疗,脂质体庆大霉素的疗效正在研究中。关于非MPS组织中的感染,具有长循环半衰期特征的隐形脂质体的适用性正在研究中。已证明这些脂质体在大鼠感染的肺组织中有大量定位。实验性细菌性肺部感染的初步数据显示,隐形脂质体包裹的抗生素疗效更佳。