Design of Phage-Cocktail–Containing Hydrogel for the Treatment of Pseudomonas aeruginosa–Infected Wounds

Abstract

Recently, the treatment of infected wounds has become a global problem due to increased antibiotic resistance in bacteria. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa is often present in chronic skin infections, and it has become a threat to public health as it is increasingly multidrug resistant. Due to this, new measures to enable treatment of infections are necessary. Treatment of bacterial infections with bacteriophages, known as phage therapy, has been in use for a century, and has potential with its antimicrobial effect. The main purpose of this study was to create a phage-containing wound dressing with the ability to prevent bacterial infection and rapid wound healing without side effects. Several phages against P. aeruginosa were isolated from wastewater, and two polyvalent phages were used to prepare a phage cocktail. The phage cocktail was loaded in a hydrogel composed of polymers of sodium alginate (SA) and carboxymethyl cellulose (CMC). To compare the antimicrobial effects, hydrogels containing phages, ciprofloxacin, or phages plus ciprofloxacin were produced, and hydrogels without either. The antimicrobial effect of these hydrogels was investigated in vitro and in vivo using an experimental mouse wound infection model. The wound-healing process in different mouse groups showed that phage-containing hydrogels and antibiotic-containing hydrogels have almost the same antimicrobial effect. However, in terms of wound healing and pathological process, the phage-containing hydrogels performed better than the antibiotic alone. The best performance was achieved with the phage–antibiotic hydrogel, indicating a synergistic effect between the phage cocktail and the antibiotic. In conclusion, phage-containing hydrogels eliminate efficiently P. aeruginosa in wounds and may be a proper option for treating infectious wounds.

Bacteriophages and Green Synthesized Zinc Oxide Nanoparticles in Combination Are Efficient against Biofilm Formation of Pseudomonas aeruginosa

“…In our study, phage PA19 had a slight stimulative influence on the growth of normal cells that is in line with the results of our previous study where we saw the positive effect of the phages on wound healing [37], and with the results showing that a phage cocktail improves the healing of non-infectious wounds and stimulates cell growth (unpublished data).…”

“…The phages, PB10 and PA19, used in this work were characterized in the previous study [ 37 ]. The dilution method was used to determine the concentrations of the phages expressed as plaque-forming units (PFU/mL).…”

A thermosensitive hydrogel formulation of phage and colistin combination for the management of multidrug-resistant Acinetobacter baumannii wound infections

“…The phage MR10 and minocycline-loaded PVA–SA hydrogel wound dressing effectively reduced bacteria (∼2 log) from skin 32 and the PAS-combination (phage PEV20 + ciprofloxacin) encapsulated wound dressing of SA–CMC synergistically killed (∼95%) P. aeruginosa . 9 The appropriate hydrogel compositions (F5) could not only retain the excellent bactericidal effect of the PAS combination, but also facilitated the suppression of resistance emergence. Chronic wound infections are usually associated with negative antibiotic treatment outcomes due to the formation of robust biofilms and emergence of antibiotic-resistant bacteria.…”

“…Skin and soft tissue infections (SSTIs) are mostly caused by Escherichia coli , 7 methicillin-resistant Staphylococcus aureus (MRSA) 7,8 and Pseudomonas aeruginosa . 9 However, the rapid emergence of multidrug-resistant (MDR) Acinetobacter baumannii and the lack of effective antibiotics pose significant medical challenges to their associated SSTIs. 10,11 Also, A. baumannii traumatic wound infections have drawn significant attention due to an increase in epidemics among combat injury and natural catastrophe victims.…”

“…32 Another study showed that the combination of the phage PEV20 and ciprofloxacin encapsulated wound dressing of sodium alginate–carboxymethyl cellulose (SA–CMC) synergistically killed (∼95%) P. aeruginosa in vitro . 9 While these pre-formed hydrogels demonstrated good potential for the delivery of PAS combination, in situ hydrogels are more favorable as they cause minimum tissue damage upon application and can keep the wound environment wet to facilitate wound healing. 33,34…”