Superior chemotherapeutic efficacy of amphotericin B in tuftsin-bearing liposomes against Leishmania donovani infection in hamsters
Superior chemotherapeutic efficacy of amphotericin B in tuftsin-bearing liposomes against Leishmania donovani infection in hamsters
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DOI：
10.1080/10611860290007513
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发表时间：
2002-02-01
影响因子：
4.5
通讯作者：
Gupta, CM
中科院分区：
文献类型：
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作者：
Agrawal, AK;Agrawal, A;Gupta, CM
在杜氏利什曼原虫感染的仓鼠中，在将药物包封在不含簇蛋白酶的脂质体以及携带簇蛋白酶的脂质体中后，检测了作为治疗对使用锑剂的常规化学疗法产生抗性的利什曼原虫感染（黑热病）的选择药物的利什曼菌素B（PIB B）的化学治疗功效。通过在不含簇蛋白酶的脂质体中递送β B，活性显著增加（p < 0.05）。通过在脂质体表面接枝天然巨噬细胞激活剂四肽，tuftsin（Thr-Lys-Pro-Arg），脂质体化的B-B B的这种抗利什曼原虫作用进一步增加（p < 0.05）。这可能归因于脂质体化后增强的药物耐受性以及巨噬细胞对载有tuftsin的脂质体的摄取增加。除了增加的功效之外，在携带簇蛋白的脂质体中包封抗肿瘤B还增强了药物对游离药物以其他方式不可及的区域（例如骨髓）的可及性。这些结果进一步证明了携带簇蛋白的脂质体作为药物载体在治疗最近综述的基于巨噬细胞的感染中的有用性（Agrawal，A.K.和Gupta，C.M.（2000年）的第10/2000号决议。Tuftsin-bearing脂质体治疗巨噬细胞感染，Adv. Drug Deliv.版本号：41，135-146）。
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).