Antimicrobial effectiveness of liposomal polymyxin B against resistant Gram-negative bacterial strains
Antimicrobial effectiveness of liposomal polymyxin B against resistant Gram-negative bacterial strains
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DOI：
10.1016/j.ijpharm.2007.11.035
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发表时间：
2008-05-01
影响因子：
5.8
通讯作者：
Suntres, Zacharias E.
中科院分区：
文献类型：
--
作者：
Alipour, Misagh;Halwani, Majed;Suntres, Zacharias E.
多粘菌素B是一种多阳离子抗生素，可有效治疗革兰氏阴性细菌感染。由于多粘菌素B的毒性，尤其是肾毒性、耳毒性和神经肌肉阻断，其全身应用一直受到限制。众所周知，将抗生素包埋在脂质体中可以增强其抗菌活性，同时将其毒性作用降至最低。在本研究中，将多粘菌素B与1，2-二棕榈酰甘油-3-磷胆碱(DPPC)和胆固醇(CHOL)或1-palmitoyi-2-oleoyl-sn-glycero-3-phosphocholine(POPC)和CHOL组成脂质体。含DPPC/Chol的超声脂质体的包封率(32.1+/-2.43%)是含POPC/Chol的脂质体(5.35+/-0.32%)的6倍。而挤压型DPPC/Chol脂质体的包封率(3.23+/-0.46%)比由POPC/Chol组成的脂质体(5.10+/-0.37%)低约30%。将含有多粘菌素B的挤压DPPC/Chol脂质体在37℃的血清中孵育，3h后抗生素完全释放到上清液中，而POPC/Chol脂质体在3h后完全释放抗生素。在37℃下孵育48h后，DPPC/Chol脂质体中多粘菌素B的自发释放率(66%)显著高于POPC/Chol脂质体中的自发释放率(24%)。关于脂质体多粘菌素B制剂的抗菌活性，超声化的DPPC/Chol脂质体对革兰氏阴性菌的MIC值一般低于游离多粘菌素B。免疫细胞化学和电子显微镜研究表明，多粘菌素B作为脂质体给药后，其对耐药铜绿假单胞菌的渗透率高于其常规形式。游离药物与普通脂质体的组合具有与游离抗生素相似的抗菌活性。这些数据表明，在脂质体中掺入多粘菌素B可能有助于治疗由这些微生物引起的革兰氏阴性感染。(C)2007 Elsevier B.V.保留所有权利。
Polymyxin B is a polycationic antibiotic effective in the treatment of Gram-negative bacterial infections. Systemic use of polymyxin B has been limited due to its toxicity, most notably nephrotoxicity, ototoxicity, and neuromuscular blockade. Entrapment of antibiotics in liposomes is known to enhance their antimicrobial activities while minimizing their toxic effects. In the present study, polymyxin B was incorporated into liposomes composed of either 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol (Chol) or 1-palmitoyi-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and Chol. The entrapment efficiency of sonicated liposomes containing DPPC/Chol (32.1 +/- 2.43%) was six-fold higher than that of liposomes containing POPC/Chol (5.35 +/- 0.32%). On the other hand, the entrapment efficiency of extruded DPPC/Chol liposomes (3.23 +/- 0.46%) was about 30% less than that of liposomes composed of POPC/Chol (5.10 +/- 0.37%). Incubation of extruded DPPC/Chol liposomes containing polymyxin B in serum at 37 degrees C resulted in a complete release of the antibiotic into the supernatant after 3 h as compared to 6 h in the case of POPC/Chol liposomes. Spontaneous release of polymyxin B from DPPC/Chol liposomes incubated in saline was significantly higher (66%) than that from POPC/Chol liposomes (24%) after 48 h at 37 degrees C. With respect to the antimicrobial activities of the liposomal polymyxin B formulations, the MICs of sonicated DPPC/Chol liposomes against Gram-negative strains were generally lower when compared to free polymyxin B. Immunocytochemistry and electron transmission microscopic studies revealed that the penetration of polymyxin B into a resistant strain of Pseudomonas aeruginosa was higher following its administration as a liposomal formulation as compared to its conventional form. The combination of free drug and plain liposomes had an antibacterial activity similar to that of free antibiotic. These data suggest that incorporation of polymyxin B in liposomes could be useful in the management of Gram-negative infections induced by these microorganisms. (C) 2007 Elsevier B.V. All rights reserved.