Today modern hospitalization is the occurrence of nosocomial or healthcare acquired infections caused by MDR pathogens . PAMAM dendrimers have been investigated for their biological applications, but antibacterial activity has not been extensively explored [17, 24]. In this work, we used disc diffusion and broth microdilution (MIC and MBC determination) methods to assess the antibacterial activity of PAMAM-G7 against eight most common human pathogens isolated from clinical specimens, as well as standard strains. S. aureus is a microorganism causing a wide range of infections from local infections of skin and soft tissue to pneumonia and endocarditis . A. baumannii is an important human pathogen causing hospital-acquired infections, such as ventilator associated pneumonia, bacteremia, meningitis, urinary tract, and wound infections . E. coli strains are responsible for several forms of diarrheal disease  and meningitis in neonates . P. aeruginosa is inherently resistant to drugs because of its less permeable cell wall and a variety of efflux pumps . K. pneumoniae can be found commonly in humans and animals’ mouth, skin, and intestines as an opportunistic pathogen, frequently causing pneumonia, infection of the urinary tract, and soft tissues .
The infections caused by S. dysenteriae and Proteus mirabilis had a serious clinical problem. S. dysenteriae is the cause of brisk and deadly epidemics and pose major health problems in the poorest populations. Alternative therapeutic strategies are necessarily in search due to the emergence of MDR in Shigellae . Antibacterial properties of PAMAM-G7 dendrimer was checked also against B. subtilis. B. subtilus is not a common HCAI organism, but it was used as a representative for spore-forming bacteria . The size of the inhibition zone clearly shows that with increasing concentrations of the PAMAM-G7 NPs, the surrounding zone of the discs is expanded (Tables 2 and 3). The results of this study showed that very low concentrations (0.025 μg/disc) of the dendrimer PAMAM-G7 inhibits the growth of the P. mirabilis and S. aureus isolates (Tables 2 and 3). The study carried out by Izanloo et al. , by disc diffusion method on the effect of dendrimer PAMAM-G4 on E. coli, Enterobacter cloacae, B. subtilis and S. aureus, concluded that concentration of 0.05 μg/disc has no effect on these bacteria and it was shown that the antibacterial effect of PAMAM-G4 takes place in higher concentrations. Izanloo et al. , in another study which was carried out by disc diffusion method and was aimed to evaluate the effect of PAMAM-G4 dendrimer on Klebsiella oxytoca, P. mirabilis and P. aeruginosa, has showed that concentrations of 0.5, 5 and 50 μg/disc of PAMAM-G4 has no effect on these selected bacteria. Probably, the higher antibacterial effect of PAMAM-G7 dendrimer in comparison to lower generation dendrimers can be attributed to high density, ordered, hyper branching structure, high spatial void between branches, large number of terminal functional groups and relatively large molecular size of PAMAM-G7 . These characteristics lead to high surface area in dendrimer PAMAM-G7 which causes higher activity of dendrimers in surface of culture and higher efficiency at lower concentrations. Figure 4 shows a SEM image of dendrimer PAMAM-G7. Because of their multi-layered structures with high purity, they can trap and absorb many microbial agents. Dendritic structures known as dendriform with progressive structure are illustrated in this figure. Too many branches of this dendriform lead to increase in the dendrimer surface area therefore they absorb microbes on their surface. On the other hand, nano holes created between branches trap biological agents and destroy them. But most importantly, it is the number of terminal amine groups, which for generation 4 is 64, while the number of terminal amine groups for PAMAM-G7 is 512 (http://www.dendritech.com/pamam.html) . These functional groups are adsorbed on the bacterial cell surfaces, diffused through the cell wall, bonded to cytoplasmic membrane and release electrolytes such as potassium ions and phosphate from the cell, also nucleic materials such as DNA and RNA due to disruption and disintegrate of the cytoplasmic membrane. Therefore it is proposed that the antibacterial property of dendrimers is mediated by disrupting the bacterial outer and inner membrane by terminal amine groups [17, 36].
According to MIC or MBC values (Tables 4 and 5), it is clear that PAMAM-G7 has antibacterial effects and can be used as antibacterial agent. Previous studies have been shown that these antibacterial agents cause bacterial cell membrane damage, spatial deformation, degradation of bacterial enzymes, damage of chromosome and bacteria cell wall damage [15, 37]. This character refers to end amine groups in dendrimer structure which interact with negative charge of membrane or microorganism cytoplasm, causing bacterial cell wall damage and finally, inactivation of bacteria . Figure 2 shows the FTIR spectra of PAMAM-G7 dendrimer. As shown, 9 peaks are detectable at 1032 cm−1, 1365 cm−1, 1462 cm−1, 1546 cm−1, 1654 cm−1, 2828 cm−1, 2942 cm−1 3280 cm−1 and 3407 cm−1which the last peak is related to N-H stretching vibration of primary amine. Other main band positions, based on wavenumber, and their assignments are presented in Table 1.
Thus, the PAMAM-G7 dendrimer is an efficient antibacterial agent for both Gram-negative and Gram-positive bacteria. Chen et al. , observed the antibacterial effect of polypropyleneimine dendrimer modified with quaternary ammonium groups on Gram-positive and Gram-negative bacteria. Likewise, Xue. et al. and Charles. et al., have shown that amino-terminated PAMAM-G2 and G3 dendrimers possess significant antibacterial effects on MDR strains [14, 15].
As shown in Tables 2, 3, 4 and 5, the E. coli, P. aeruginosa, A. baumannii and S. aureus had a higher resistance than other studied bacteria. Probably the effect of lower concentrations of dendrimer PAMAM-G7 on the bacteria such as E. coli, P. aeruginosa, A. Baumannii and S. aureus than other target bacteria can be due to intrinsic resistance of these bacteria [5, 39, 40].
Also, the cytotoxicity of PAMAM-G7 was investigated on HCT 116 and NIH 3 T3 cell lines (mammalian cells). The obtained data (Figs. 5 and 6) show that by increasing both concentration and exposure time the cytotoxity effect on target cells increases.
Mukherjee et al.  indicated different generations (G4, G5 and G6) of PAMAM dendrimers with variety of doses which increasing dose and generation of these dendrimers cause decrease in the percentage of healthy and early apoptotic cell which increasing dose and generation of these dendrimers cause decrease in the percentage of healthy and early apoptotic cell. At high concentrations, PAMAM can lead to the formation of nanoscale holes in eukaryotic membranes [22, 41, 42]. Highly branched cationic polymers permeate eukaryotic membranes better than linear molecules, such as LL-37 , so PAMAM dendrimers are more toxic for eukaryotic cells. This property of branched polymers has been widely used in foreign gene or drug transfaction in eukaryotic cells . The charge density on the polymer also plays an important role in permeability . After 72 h of treatment at the highest concentration of PAMAM-G7 (0.85 μM), 55.37 and 57% of HCT116 and NIH 3 T3 cells survived, respectively (Figs. 5 and 6). The value of obtained MIC50, MIC90 (2–4 and 4–8 μg/ml, respectively) and MIC for standard strains (2 μg/ml) for both Gram-positive and Gram-negative bacteria, showed, PAMAM-G7 at relatively lower concentrations, has high toxic effect on both Gram-negative and Gram-positive bacteria.
However in 0.086 μM (10 μg/ml) PAMAM-G7 and after 48 and 72 h, 84 and 77% of HCT 116 cells were survived, respectively (Fig. 5). Also in same condition 85.61 and 79.24% of NIH 3 T3 cells were survived, respectively (Fig. 6).
Furthermore the most important attachment is great toxicity of PAMAM-G7 on Gram-negative and Gram positive bacteria. However PAMAM-G7 has relatively low toxicity on HCT 116 and NIH 3 T3 cells. To further elucidate this observation, it was noted that the polycationic PAMAM molecules prefer to bind to bacteria cells that carry a higher density of negative charges on their surfaces rather than eukaryote cell lines.
Initial electrostatic interaction, followed by further interactions, including hydrophobic interactions between the dendrimers and cell membrane, are shown to be necessary to cause cell lysis, since it has been shown that surfaces presenting a high density of amino groups have no marked effect on the membrane of the attached bacteria [17, 42].
However, various studies have shown that, PAMAM dendrimers show relatively high toxicity against various eukaryotic cells. But the notable point is that, most studies regarding the use of PAMAM dendrimers, are in the field of drug delivery and gene transfection. The high amount of dendrimers is required on drug and gene delivery so, such studies indicate the high toxic effect of PAMAM dendrimers on eukaryotic [43, 44], the cytotoxicity of PAMAM dendrimers, often investigates in higher concentrations. In a study the toxic effect of different PAMAM dendrimers (G3, 3.5, 4, 4.5, and) generations on HepG2 and DU145 cell lines was investigated. It indicate, HepG2 were less sensitive than DU145 cells with IC50 values ≥ 402 μM (PAMAMs) and ≤13.24 μM (PAMAMs) for DU145 . In another study the cytotoxicity of various PAMAM dendrimers (G4, G5, G6) generations on HaCaT and SW480 cells was measured by MTT assay, after 24 h exposure it was found that, EC50 concentrations for PAMAM G4, G5 and G6 in SW480 cells were equal to 1.44, 0.37 and 1.16 μM, respectively, and for HaCaT cells were equal to 1.02, 1.07, and 3.21 μM, respectively .