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噬菌体负载纳米结构脂质载体:改善药代动力学介导有效解决肺炎克雷伯菌引起的大叶性肺炎。

Bacteriophage-loaded nanostructured lipid carrier: improved pharmacokinetics mediates effective resolution of Klebsiella pneumoniae-induced lobar pneumonia.

机构信息

Department of Microbiology.

University Institute of Pharmaceutical Science, Panjab University, Chandigarh, India.

出版信息

J Infect Dis. 2015 Jul 15;212(2):325-34. doi: 10.1093/infdis/jiv029. Epub 2015 Jan 20.

Abstract

This study examined the therapeutic and prophylactic potential of bacteriophages in a mouse model of Klebsiella pneumoniae lobar pneumonia. Phages were administered intraperitoneally. Liposome-entrapped phages (LP) were effective in treating infection, even when therapy was delayed by 3 days after the induction of pneumonia. In contrast, nonliposomal phages provided protection when administered 24 hours after infection. Administration of nonliposomal phages 6 hours prior to intranasal bacterial challenge resulted in complete protection, compared with LP, which was effective even when administered 48 hours prior to infection. Increased reduction and a greater increment in the levels of proinflammatory and antiinflammatory cytokines, respectively, in homogenates of lung from LP-treated mice were suggestive of increased efficacy of LP in the treatment of pneumonia. This is the first study to assess liposomes as a delivery vehicle for phage, and the results confirm the superiority of LP for both therapeutic and prophylactic applications.

摘要

本研究在肺炎克雷伯菌肺叶炎的小鼠模型中考察了噬菌体的治疗和预防潜力。噬菌体通过腹腔内给药。脂质体包封的噬菌体(LP)在治疗感染方面非常有效,即使在肺炎诱导后 3 天开始治疗也有效。相比之下,非脂质体噬菌体在感染后 24 小时给药时提供保护。与 LP 相比,在鼻内细菌攻击前 6 小时给予非脂质体噬菌体可完全保护,而 LP 在感染前 48 小时给药时仍有效。LP 治疗的小鼠肺匀浆中促炎和抗炎细胞因子的水平分别增加,提示 LP 在治疗肺炎方面的疗效更高。这是首次评估脂质体作为噬菌体传递载体的研究,结果证实了 LP 在治疗和预防应用中的优越性。

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