1. Levofloxacin and indolicidin for combination antimicrobial therapy
Khairunnisa Abdul Ghaffar, Waleed M Hussein, Zeinab G Khalil, Robert J Capon, Mariusz Skwarczynski, Istvan Toth Curr Drug Deliv. 2015;12(1):108-14. doi: 10.2174/1567201811666140910094050.
Despite the increasing need for antibiotics to fight infectious diseases, fewer new antibiotics are available on the market. Unfortunately, developing a new class of antibiotics is associated with high commercial risk. Therefore, modification or combination of existing antibiotics to improve their efficacy is a promising strategy. Herein, we conjugated the antibiotic, levofloxacin, with two peptides, i.e. an antimicrobial peptide indolicidin and a cell penetrating peptide (TAT). Glycolic acid and glycine linkers were used between levofloxacin and peptides. We developed an optimized condition for coupling of levofloxacin via its carboxylic group to glycolic acid using solid phase peptide synthesis (SPPS). Antibacterial and haemolytic assays were carried out on the conjugates and only the levofloxacin-indolicidin conjugate demonstrated moderate antibacterial activity. Interestingly, physical mixture of levofloxacin and indolicidin showed improvement in the activity against Gram-positive bacteria.
2. Gold Nanoparticles Conjugated Levofloxacin: For Improved Antibacterial Activity Over Levofloxacin Alone
Paramdeep Bagga, Hifazat Hussain Siddiqui, Juber Akhtar, Tariq Mahmood, Manaal Zahera, Mohd Sajid Khan Curr Drug Deliv. 2017;14(8):1114-1119. doi: 10.2174/1567201814666170316113432.
Background: Levofloxacin is a potent antibiotic with severe side effects due to its high doses. Bacterial resistance may be due to frequent use of antibiotics. Biogenic gold nanoparticles conjugated levofloxacin (Au-HSA-LvN-NPs) were developed by Human Serum Albumin (HSA) and nitrate reductasemediated pathways. Methods: Au-HSA-LvN-NPs (size = 27.2 ± 1 nm) were readily generated with high emulsion stability zeta potential (-13.3 mV). The developed nanoparticles were also characterized by UVvisible spectroscopy, Transmission Electron Microscopy and Dynamic Light Scattering techniques. Results: The optimized nanoparticles were found efficient against both Gram-positive bacteria and Gramnegative bacteria specifically S. aureus (MIC-0.373 µg/ml), E. coli (MIC-0.149 µg/ml) and P. aeruginosa (MIC-0.346 µg/ml) respectively. Conclusion: The efficiency of bioconjugated levofloxacin got improved by 1.94 times, 2.89 times and 1.46 times against S. aureus, E. coli and P. aeruginosa respectively, in comparison to pure levofloxacin.
3. Enhanced activity of vancomycin by encapsulation in hybrid magnetic nanoparticles conjugated to a cell-penetrating peptide
Wenjie Zhang, Reza Taheri-Ledari, Zoleikha Hajizadeh, Ehsan Zolfaghari, Mohammad Reza Ahghari, Ali Maleki, Michael R Hamblin, Ye Tian Nanoscale. 2020 Feb 14;12(6):3855-3870. doi: 10.1039/c9nr09687f. Epub 2020 Jan 30.
We describe a novel antibiotic delivery system based on magnetic nanoparticles (NPs) conjugated to a cell-penetrating peptide (CPP). Silica-coated iron oxide NPs were produced via a co-deposition method, and coated by a polyvinyl alcohol (PVA) polymeric network via physicochemical binding. Vancomycin (VAN) was then entrapped into this PVA network. A hexapeptide sequence Gly-Ala-Phe-Pro-His-Arg, was synthesized in the solid phase and then conjugated onto the surface of the magnetic NPs. The drug ratio incorporation into the carrier system and drug release were monitored through precise analysis. Confocal microscopy showed that the NPs could be internalized into Staphylococcus aureus and Escherichia coli bacterial cells. The antimicrobial effects of VAN were significantly enhanced by this system with a low dosage of VAN. Advantages include rapid targeted-drug delivery process, drug dose reduction, and equal effects on both Gram-positive and Gram-negative bacteria.
