PAMAM-dendrimer Enhanced Antibacterial Effect of Vancomycin Hydrochloride Against Gram-Negative Bacteria (original) (raw)
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In vitro antibacterial activity of poly (amidoamine)-G7 dendrimer
BMC Infectious Diseases
Background: Nano-scale dendrimers are synthetic macromolecules that frequently used in medical and health field. Traditional anibiotics are induce bacterial resistence so there is an urgent need for novel antibacterial drug invention. In the present study seventh generation poly (amidoamine) (PAMAM-G7) dendrimer was synthesized and its antibacterial activities were evaluated against representative Gram-negative and Gram-positive bacteria. Methods: PAMAM-G7 was synthesized with divergent growth method. The structural and surface of PAMAM-G7 were investigated by transmission electron microscopy, scanning electron microscope and fourier transform infrared. Pseudomonas. aeruginosa (n = 15), E. coli (n = 15), Acinetobacter baumanni (n = 15), Shigella dysenteriae (n = 15), Klebsiella pneumoniae (n = 10), Proteus mirabilis (n = 15), Staphylococcus aureus (n = 15) and Bacillus subtilis (n = 10) have been used for antibacterial activity assay. Additionally, representative standard strains for each bacterium were included. Minimum Inhibitory Concentration (MIC) was determined using microdilution method. Subsequently, Minimum Bactericidal Concentration (MBC) was determined by sub-culturing each of the no growth wells onto Mueller Hinton agar medium. The cytotoxicity of PAMAM-G7 dendrimer were evaluated in HCT116 and NIH 3 T3 cells by MTT assay. Results: The average size of each particle was approximately 20 nm. PAMAM-G7 was potentially to inhibit both Gram positive and gram negative growth. The MIC50 and MIC90 values were determined to be 2-4 μg/ml and 4-8 μg/ml, respectively. The MBC50 and MBC90 values were found to be 64-256 μg/ml and 128-256 μg/ml, respectively. The cytotoxity effect of dendrimer on HCT116 and NIH 3 T3 cells is dependent upon exposure time to and concentration of dendrimers. The most reduction (44.63 and 43%) in cell viability for HCT116 and NIH 3 T3 cells was observed at the highest concentration, 0.85 μM after 72 h treatmentm, respectively. Conclusions: This study we conclude that PAMAM-G7 dendrimer could be a potential candidate as a novel antibacterial agent.
Synthesis and Biological Activity of Highly Cationic Dendrimer Antibiotics
Molecular Pharmaceutics, 2016
The development of pathogenic bacteria resistant to current treatments is a major issue facing the world today. Here, the synthesis and biological activity of fourth generation poly(amidoamine) dendrimers decorated with 1-hexadecyl-azoniabicylo[2.2.2]octane (C 16-DABCO), a quaternary ammonium compound known to have antibacterial activity, are described. This highly cationic dendrimer antibiotic was tested against several Gram positive and Gram negative strains of pathogenic bacteria and exhibited activity against both. Higher activity toward the Gram positive strains that were tested was observed. After the antimicrobial activity was assessed, E. coli and B. cereus were subjected to a resistance selection study. This study demonstrated that a multivalent approach to antimicrobial design significantly reduces the likelihood of developing bacterial resistance. Highly cationic dendrimers were also used as pretreatment of a membrane in order to prevent biofilm formation.
The AAPS Journal, 2012
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 dosedependently 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.
Molecules, 2013
Erythromycin (EM) and tobramycin (TOB) are well-known and widely used antibiotics, belonging to different therapeutic groups: macrolide and aminoglycoside, respectively. Moreover, they possess different solubility: EM is slightly soluble and TOB is freely soluble in water. It was previously demonstrated that PAMAM dendrimers enhanced the pharmacological activity of antifungal drugs by increasing their solubility. Therefore, it appears interesting to investigate the effect of PAMAM-NH 2 and PAMAM-OH dendrimers generation 2 (G2) and generation 3 (G3) on the antibacterial activity of antibiotics with different water solubility. In this study it was shown that the aqueous solubility of EM was significantly increased by PAMAM dendrimers (PAMAM-NH 2 and PAMAM-OH caused about 8-and 7-fold solubility increases, respectively). However, it was indicated that despite the increase in the solubility, there was only slight influence on the antibacterial activity of EM (2-and 4-fold decreases in the MBC values of EM in the presence of PAMAM-OH G3 and PAMAM-NH 2 G2 or G3 for strains of Staphylococcus aureus were noted, respectively). It was also found that there was no influence of PAMAM on the antibacterial activity of hydrophilic TOB.
Journal of Nanomaterials
Dendrimers are potent synergists, carriers, and delivery molecules for natural biological products and pharmaceuticals. Staphylococcus aureus (S. aureus) infection is causing serious diseases in humans and animals. Given the recorded antibacterial and antiviral activity of terminal-charged PAMAM dendrimers, the relation between dendrimer charge type and generation is to be established against S. aureus. Three types of polyanionic dendrimers comprising terminal groups sodium carboxylate (generations 1.5, 2.5, 3.5, and 4.5), hydroxyl (generations 2, 3, 4, and 5), and succinamic acid (generations 2, 3, 4, and 5) and polycationic dendrimers containing primary amine (generations 2, 3, 4, and 5) were in antibacterial assays to determine their zone of inhibition and antibacterial activity. Cationic dendrimers were more potent than anionic dendrimers. The largest inhibition was shown by G(5)-128NH2 followed by G(4)-64NH2 primary amine dendrimers. Carboxylate, hydroxyl, and succinamic acid d...
Surface modification of poly(amidoamine) (PAMAM) dendrimer as antimicrobial agents
Tetrahedron Letters, 2012
Poly(amidoamine) (PAMAM) (G3) dendrimer was modified into quaternary ammonium salts using tertiary amines with different chain lengths: dimethyldodecyl amine, dimethylhexyl amine, and dimethylbutyl amine using an efficient synthetic route. The antimicrobial activity of these dendrimer ammonium salts against Staphylococcus and E-coli bacteria was examined using the disc diffusion method. It was found that quaternary ammonium salt prepared with the dimethyldodecyl amine exhibits antimicrobial efficacy against Staphalococus and E.coli bacteria.
Synthesis, characterization and antimicrobial activity of water soluble dendritic macromolecules
European journal of medicinal chemistry, 2009
Several families of water soluble dendrimers were synthesized based on poly(propyleneoxide) amines (Jeffamines) (P(1)). P(1)-core and branched units were constructed from both methylacrylate and ethylenediamine (P(2)-P(9), and generations 0-3 with -NH(2), -COOH functionalities). They were characterized by elemental analysis (EA), gel permeation chromatography (GPC), FT-IR, (1)H, and (13)C NMR. The antimicrobial activities of only water soluble compounds (P(1), P(3), P(4), P(6), P(7) and P(9)) were evaluated using disk diffusion method in water as well as the minimal inhibitory concentration (MIC) dilution method against 9 bacteria. The obtained results from disk diffusion method are assessed in side-by-side comparison with those of Penicillin-g, Ampicillin, Cefotaxime, Vancomycin, Oflaxacin, and Tetracycline, well-known antibacterial agents. The results from dilution procedure are compared with Gentamycin as antibacterial and Nystatin as antifungal. The antifungal activities are rep...
6 Dendrimers as Antibacterial Agents
2018
No more than 100 years ago, if a person acquired a bacterial infection, the body had to clear the infection by itself or else the infection would eventually result in death. After penicillin and many other effective antibiotics were discovered, however, that changed. In the decades after penicillin was discovered in 1928, a number of powerful antibiotics were developed. They were used plentifully and often carelessly prescribed needlessly for certain bacterial infections and even for viral infections where they have no effect. Farmers found that animals fed low levels of antibiotics grow faster and are less subject to disease, so thousands of tons of antibiotics were (and still are) added to animal feed. The problem: unlike disinfectants, antibiotics generally act against a single component of a bacterium. Thus, in environments where antibiotics are present, there is great selective pressure toward bacteria that can make the relatively minor mutations needed to render them resistant...