Banerjee G, Medda S, Basu M K
Biomembrane Division, Indian Institute of Chemical Biology, Calcutta.
Antimicrob Agents Chemother. 1998 Feb;42(2):348-51. doi: 10.1128/AAC.42.2.348.
The interaction of chemotactic peptide (e.g., fMet-Leu-Phe)-grafted liposomes with macrophages is noted to be rapid and specific. At a grafted peptide concentration of 100 nmol, internalization of the peptide-grafted liposomes by the macrophages is found to reach equilibrium in 30 min. The peptide alone and the peptide-grafted empty liposomes are found to show moderate antileishmanial activity in vitro. Primaquine, which is known to generate O2- in phagocytic cells, showed leishmanicidal properties when it was tested in vitro against parasite-infected macrophages over a certain range of concentrations. It showed much better efficacy against experimental leishmaniasis when it was used in the fMet-Leu-Phe-grafted liposomal form in comparison with its efficacy when it was either in the free form or encapsulated in ungrafted liposomes. The conventional toxicity parameters (e.g., blood pathology and tissue histology-specific enzyme levels related to normal liver function) are found to be very close to normal when fMet-Leu-Phe-grafted liposomal primaquine is used. The biodegradabilities of both the drug and the delivery systems are also found to be very satisfactory. Thus, this delivery system may have possible applications for the treatment of leishmaniasis as well as other macrophage-associated disorders.
趋化肽（如甲酰甲硫氨酸-亮氨酸-苯丙氨酸）修饰的脂质体与巨噬细胞的相互作用迅速且具有特异性。在修饰肽浓度为100 nmol时，巨噬细胞对肽修饰脂质体的内化作用在30分钟内达到平衡。单独的肽和肽修饰的空脂质体在体外显示出中等程度的抗利什曼原虫活性。已知能在吞噬细胞中产生超氧阴离子的伯氨喹，在一定浓度范围内对感染寄生虫的巨噬细胞进行体外测试时表现出杀利什曼原虫特性。与以游离形式或包裹在未修饰脂质体中的情况相比，当以甲酰甲硫氨酸-亮氨酸-苯丙氨酸修饰的脂质体形式使用时，它对实验性利什曼病显示出更好的疗效。当使用甲酰甲硫氨酸-亮氨酸-苯丙氨酸修饰的脂质体形式的伯氨喹时，发现常规毒性参数（如与正常肝功能相关的血液病理学和组织组织学特异性酶水平）非常接近正常。药物和递送系统的生物降解性也非常令人满意。因此，这种递送系统可能在治疗利什曼病以及其他与巨噬细胞相关的疾病方面具有潜在应用。
