Rajiv Pathak

Multifunctional self-assembled cationic peptide nanostructures efficiently carry plasmid DNA in vitro and exhibit antimicrobial activity with minimal toxicity

In this study, a modified dehydropeptide, Boc-FΔF-εAhx-OH, was conjugated with an aminoglycoside antibiotic, neomycin, to construct a multifunctional conjugate, Pep-Neo. The amphiphilic conjugate (Pep-Neo) was able to self-assemble into cationic nanostructures in an aqueous solution at low concentrations. Nanostructure formation was evidenced by TEM and dynamic light scattering analyses. The average hydrodynamic diameter of the self-assembled Pep-Neo nanostructures was found to be ∼279 nm with a zeta potential of +28 mV. The formation of nanostructures with a hydrophobic core and cationic hydrophilic shell resulted in an increased local concentration of cationic charge (ca. in 50% aqueous methanol, i.e. disassembled structure, zeta potential decreased to +17.6 mV), leading to efficient interactions with negatively charged plasmid DNA (pDNA). The size and zeta potential of the resulting Pep-Neo/pDNA complex were found to be ∼154 nm and +19.4 mV, respectively. Having been characterized by physicochemical techniques, the complex was evaluated for its toxicity and ability to deliver nucleic acid therapeutics. The flow cytometry results on MCF-7 cells revealed that Pep-Neo/pDNA complex transfected ∼27% cells at a w/w ratio of 66.6 while the standard transfection reagent, Lipofectamine, could transfect only ∼15% cells. MTT and hemolysis assays showed the non-toxic nature of the projected conjugate at various concentrations. Further, these nanostructures were shown to encapsulate hydrophobic drugs in the core. Finally, Pep-Neo nanostructures showed efficient antibacterial activity against different strains of Gram-positive and -negative bacteria. Interestingly, unlike neomycin, which is highly effective against Gram-negative bacteria, these nanostructures showed considerably high efficiency against Gram-positive strains, highlighting the promising potential of these nanostructures for various biomedical applications.

Synthesis and antimicrobial activity of aminoglycoside-conjugated silica nanoparticles against clinical and resistant bacteria

Functionalization of silica nanoparticles with different cationic moieties makes them suitable for being an effective antimicrobial agent against various clinical pathogenic microbes. Here, we report the synthesis, characterization and evaluation of aminoglycoside-conjugated silica nanoparticles [S–X NPs, where X = gentamicin (G), neomycin (N) or kanamycin (K)] for their antimicrobial activity against clinical pathogens and kanamycin-resistant E. coli. These functionalized silica nanoparticles exhibited enhanced broad-spectrum antimicrobial activity against clinical Gram-positive and Gram-negative bacteria as well as kanamycin-resistant E. coli strain with minimal cytotoxicity. The results show the potential of these conjugates to combat drug resistance.

Enhanced Antimicrobial Activity of Amine-Phosphonium (N-P) Hybrid Polymers Against Gram-Negative and Gram-Positive Bacteria

The authors report synthesis, characterization and evaluation of a series of linear polyethylenimine (lPEI)-grafted butyltriphenylphosphonium bromide (LBTP) polymers (N-P hybrid polymers) for their antimicrobial activity on various Gram-positive and Gram-negative bacteria. Polymers with ∼5.8–13.8% substitution of butyltriphenylphosphonium bromide (BTP) on the backbone of lPEI showed enhanced charge density as compared to native lPEI confirming the conjugation of BTP onto lPEI. These modified polymers displayed low hemolytic activity and excellent antimicrobial activity against these two types of bacteria with one of the modified polymers, LBTP-40, was found to exhibit high antimicrobial activity in all the strains. GRAPHICAL ABSTRACT

Evaluation of antimicrobial efficacy of quaternized poly[bis(2-chloroethyl)ether-alt-1,3-bis[3-(dimethylamino)propyl]urea] against targeted pathogenic and multi-drug-resistant bacteria

Here, we have investigated in vitro antimicrobial efficacy of a quaternized cationic polymer, poly[bis(2-chloroethyl)ether-alt-1,3-bis[3-(dimethylamino)propyl]urea] (polyquaternium-2), against gram-positive as well as gram-negative bacteria along with several multi-drug-resistant bacterial strains. The antimicrobial efficacy of this polymer was first tested against some clinical pathogens followed by microorganisms isolated from acne lesions. Interestingly, polyquaternium-2 exhibited significant antimicrobial activity against methicillin-resistant Staphylococcus aureus, for which very limited drugs are available. Most importantly, the polymer displayed low haemolytic activity and non-toxic behaviour against mammalian cells. The results showed the promising potential of the projected polymer to be utilized as an antibacterial agent for various biomedical applications.

Multifunctional biosynthesized silver nanoparticles exhibiting excellent antimicrobial potential against multi-drug resistant microbes along with remarkable anticancerous properties

This study demonstrates the therapeutic potential of silver nanoparticles (AgNPs), which were biosynthesized using the extracts of Citrus maxima plant. Characterization through UV-Vis spectrophotometry, Dynamic Light Scattering (DLS), Fourier Transform Infrared spectroscopy (FTIR), X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) confirmed the formation of AgNps in nano-size range. These nanoparticles exhibited enhanced antioxidative activity and showed commendable antimicrobial activity against wide range of microbes including multi-drug resistant bacteria that were later confirmed by TEM. These particles exhibited minimal toxicity when cytotoxicity study was performed on normal human lung fibroblast cell line as well as human red blood cells. It was quite noteworthy that these particles showed remarkable cytotoxicity on human fibrosarcoma and mouse melanoma cell line (B16-F10). Additionally, the apoptotic topographies of B16-F10 cells treated with AgNps were confirmed by using acridine orange and ethidium bromide dual dye staining, caspase-3 assay, DNA fragmentation assay followed by cell cycle analysis using fluorescence-activated cell sorting. Taken together, these results advocate promising potential of the biosynthesized AgNps for their use in therapeutic applications.