Agrawal Ajay K, Agrawal A, Pal A, Guru P Y, Gupta C M
Central Drug Research Institute, Lucknow, India.
J Drug Target. 2002 Feb;10(1):41-5. doi: 10.1080/10611860290007513.
Chemotherapeutic efficacy of the amphotericin B (Amp B), which is the drug of choice for treatment of the leishmanial infections (kala-azar) that become resistant to the conventional chemotherapy using antimonials, has been examined in the Leishmania donovani infected hamsters after encapsulating the drug in tuftsin-free as well as tuftsin-bearing liposomes. The activity was significantly increased (p < 0.05) by delivering Amp B in tuftsin-free liposomes. This antileishmanial effect of the liposomized Amp B was further increased (p < 0.05) by grafting the natural macrophage-activator tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), on the liposome's surface. This could possibly be attributed to both the enhanced drug tolerance after liposomization as well as to the increased uptake of tuftsin-bearing Amp B-laden liposomes by the macrophages. In addition to the increased efficacy, encapsulation of Amp B in the tuftsin-bearing liposomes also enhanced the drug accessibility to areas (e.g. bone marrow) that are otherwise inaccessible to the free drug. These results further demonstrate the usefulness of tuftsin-bearing liposomes as drug vehicles in treatment of the macrophage-based infections that have been reviewed recently (Agrawal, A.K. and Gupta, C.M. (2000). Tuftsin-bearing liposomes in treatment of macrophage-based infections, Adv. Drug Deliv. Rev., 41, 135-146).
两性霉素B（Amp B）是治疗对使用锑剂的传统化疗产生耐药性的利什曼原虫感染（黑热病）的首选药物。在将该药物包裹于不含促吞噬肽以及含促吞噬肽的脂质体中后，研究了其对杜氏利什曼原虫感染仓鼠的化疗效果。通过不含促吞噬肽的脂质体递送Amp B，其活性显著提高（p < 0.05）。通过将天然巨噬细胞激活四肽促吞噬肽（苏氨酸-赖氨酸-脯氨酸-精氨酸）接枝到脂质体表面，脂质体包裹的Amp B的抗利什曼原虫作用进一步增强（p < 0.05）。这可能归因于脂质体化后药物耐受性增强以及含促吞噬肽的载有Amp B的脂质体被巨噬细胞摄取增加。除了疗效提高外，将Amp B包裹于含促吞噬肽的脂质体中还增强了药物对诸如骨髓等游离药物难以到达区域的可及性。这些结果进一步证明了含促吞噬肽的脂质体作为药物载体在治疗基于巨噬细胞的感染中的有用性，最近已有相关综述（Agrawal, A.K.和Gupta, C.M.（2000年）。含促吞噬肽的脂质体在治疗基于巨噬细胞的感染中的应用，《药物递送进展综述》，41，135 - 146）。
