PAMAM-dendrimer Enhanced Antibacterial Effect of Vancomycin Hydrochloride Against Gram-Negative Bacteria

Abstract

Purpose: The antibacterial activity of some antibiotics is specific to either Gram-positive or Gram-negative bacteria. There are different mechanisms behind such insensitivities like inability of antibiotics to permeate through some bacterial membranes, as is the case for vancomycin in Gram-negative bacteria. The present investigation tries to overcome this problem by dendrimers, in order to make Gram-negative bacteria responsive to vancomycin. Methods: The effects of generations 3 (G3) and 5 (G5) polyamidoamine amine-terminated dendrimers (NH2-PAMAM), on the antibacterial activity of vancomycin, were evaluated. Vancomycin-PAMAM dendrimers complexes were prepared and their antibacterial activities were evaluated by determination of their “minimum inhibitory concentration (MIC)”, “minimum bactericidal concentration” and “fractional inhibitory concentration index” values against two Gram-positive and four Gram-negative bacteria, using broth micro-dilution method. The complexation of vancomycin and dendrimers was also assessed by in vitro release studies across dialysis tubing using a developed HPLC method. Results: Results showed that vancomycin solution was effective against Gram-positive bacteria, but, was not effective in Gram-negative ones. Vancomycin-PAMAM dendrimers exhibited significant antibacterial efficacy against Gram-negative bacteria resulting in a decline of vancomycin MIC values by about 2, 2, 4 and 64 times in E. coli, K. pneumonia, S. typhimurium and P. aeruginosa, respectively. Results also showed that enhanced effect by G5 is more than G3. Dendrimers did not affect antibacterial activity of vancomycin in Gram-positive bacteria, as no permeation problem exists here. Conclusions: The present study revealed that both G3 and G5 cationic PAMAM dendrimers are able to make Gram-negative bacteria sensitive to vancomycin, resulting in decline of MIC values up to 64 times, possibly by increasing its permeation through bacterial membrane. These results look promising for broadening the antibacterial spectrum of vancomycin and such a strategy might be used for increasing the overall life of antibiotics.

Dendronized Silver Nanoparticles as Bacterial Membrane Permeabilizers and Their Interactions With P. aeruginosa Lipopolysaccharides, Lysozymes, and Phage-Derived Endolysins

“…It is known that antibacterial properties of nanoparticles (both dendrimers and silver NPs) strongly depend on their structure, charge, size, and adsorption ability at the bacterial surface (Felczak et al, 2012; Le Ouay and Stellacci, 2015; Tang and Zheng, 2018). As potential membrane permeabilizers, the dendronized nanoparticles may also enhance the antibacterial effect of antibiotics or antimicrobial proteins, especially against gram-negative bacteria (Winnicka et al, 2013; Serri et al, 2019). Our recent work showed that poly(propylene) imine glycodendrimers improved the antimicrobial properties of phage KP27 endolysin against P. aeruginosa cells (Ciepluch et al, 2019).…”

Formulation and Optimization of Quercetin Loaded Nanosponges Topical Gel: Ex Vivo, Pharmacodynamic and Pharmacokinetic Studies

“…The viscosity of the gel was determined by Brookfield LV Viscometer [29]. The prepared quercetin loaded nanosponges gel of 5g was taken in a beaker and by selecting spindle number 64 the viscosity of the gel was noted.…”

“…10 mg of the gel was placed in 10 ml of phosphate buffer of pH 7.4 and the solution was kept aside for 24h and the solution was stirred on a magnetic stirrer (Remi equipment, Mumbai) for 30 min and filtered [29]. The absorbance of a filtered solution was measured by using a UV spectrophotometer (Shimadzu, Japan) at 372 nm.…”

Dendrimers and Dendritic Materials: From Laboratory to Medical Practice in Infectious Diseases

“…The higher local concentration of AMP allows a multivalent binding and enhances the destabilizing effect of the bacterial membrane. Dendrimers may also be used in the rapid diagnosis to discern between Gram-negative or Gram-positive bacteria, through a pH-dependent bacteria-selective aggregation occurring within 5 min of adding the dendrimer to a bacterial suspension [ 113 ]; and as carriers of different drugs such as vancomycin or agents like LED209, both specific to Gram-negative microorganisms [ 114 , 115 ].…”