NDLI: Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent

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Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent

Content Provider	Springer Nature Link
Author	Xue, Xiaoyan Chen, Xiaoqing Mao, Xinggang Hou, Zheng Zhou, Ying Bai, Hui Meng, Jingru Da, Fei Sang, Guojun Wang, Yukun Luo, Xiaoxing
Copyright Year	2012
Abstract	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.
Starting Page	132
Ending Page	142
Page Count	11
File Format	PDF
ISSN	12341234
Journal	The AAPS Journal
Volume Number	15
Issue Number	1
e-ISSN	15507416
Language	English
Publisher	Springer US
Publisher Date	2012-11-08
Publisher Institution	American Association of Pharmaceutical Scientists
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	antibacterial activity antibiotic resistance extended-spectrum beta lactamase-producing Escherichia coli methicillin-resistant Staphylococcus aureus PAMAM dendrimers Pharmacology/Toxicology Biochemistry Biotechnology Pharmacy
Content Type	Text
Resource Type	Article

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Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent

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Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent

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Amino-Terminated Generation 2 Poly(amidoamine) Dendrimer as a Potential Broad-Spectrum, Nonresistance-Inducing Antibacterial Agent