| Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent. | |
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MedLine Citation:
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PMID: 23135925 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The treatment of septicemia caused by antibiotic-resistant bacteria is a great challenge in the clinic. Because traditional antibiotics inevitably induce bacterial resistance, which is responsible for many treatment failures, there is an urgent need to develop novel antibiotic drugs. Amino-terminated Poly(amidoamine) dendrimers (PAMAM-NH(2)) are reported to have antibacterial activities. However, previous studies focused on high generations of PAMAM-NH(2), which have been found to exhibit high toxicities. The present study aimed to clarify whether low generations of PAMAM-NH(2) could be used as novel antibacterial agents. We found that generation 2 (G2.0) PAMAM-NH(2) showed significant antibacterial effects against antibiotic-sensitive and antibiotic-resistant strains but exhibited little toxicity to human gastric epithelial cells and did not induce antibiotic resistance in bacteria. Scanning and transmission electron microscopy analyses suggested that G2.0 PAMAM-NH(2) might inhibit the growth of bacteria by destroying their cell membranes. The administration of G2.0 PAMAM-NH(2) dose-dependently improved the animal survival rate of mice infected with extended-spectrum beta lactamase-producing Escherichia coli (ESBL-EC) and of animals infected with a combination of ESBL-EC and methicillin-resistant Staphylococcus aureus. A treatment regimen of 10 mg/kg of G2.0 PAMAM-NH(2) starting 12 h before inoculation followed by 10 mg/kg at 0.5 h after inoculation rescued 100% of singly infected mice and 60% of multiply infected mice. The protective effects were associated with the reduction of the bacterial titers in the blood and with the morphological amelioration of infected tissues. These findings demonstrate that the G2.0 PAMAM-NH(2) is a potential broad-spectrum and nonresistance-inducing antibiotic agent with relatively low toxicity. |
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Authors:
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Xiaoyan Xue; Xiaoqing Chen; Xinggang Mao; Zheng Hou; Ying Zhou; Hui Bai; Jingru Meng; Fei Da; Guojun Sang; Yukun Wang; Xiaoxing Luo |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-8 |
Journal Detail:
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Title: The AAPS journal Volume: - ISSN: 1550-7416 ISO Abbreviation: AAPS J Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101223209 Medline TA: AAPS J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, No.169, Changle West Road, Xi'an, 710032, Shaanxi Province, People's Republic of China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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