The potential therapeutic impact of a topical bacteriophage preparation in treating Pseudomonas aeruginosa-infected burn wounds in mice

Hanieh Piranaghl; Shiva Golmohammadzadeh; Vahid Soheili; Zahra Sabeti Noghabi; Bahram Memar; Seyede Melika Jalali; Zhila Taherzadeh; Bibi Sedigheh Fazly Bazzaz

doi:10.1016/j.heliyon.2023.e18246

The potential therapeutic impact of a topical bacteriophage preparation in treating Pseudomonas aeruginosa-infected burn wounds in mice

Heliyon. 2023 Jul 13;9(7):e18246. doi: 10.1016/j.heliyon.2023.e18246. eCollection 2023 Jul.

Authors

Hanieh Piranaghl¹, Shiva Golmohammadzadeh², Vahid Soheili¹, Zahra Sabeti Noghabi^{1

3}, Bahram Memar⁴, Seyede Melika Jalali¹, Zhila Taherzadeh⁵, Bibi Sedigheh Fazly Bazzaz^{6

1}

Affiliations

¹ Pharmaceutical Control Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
² Nanotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran.
³ Department of Biopathology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
⁴ Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁵ Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
⁶ Biotechnology Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Aim: This study compared a topical formulation containing lytic phages with a routine antibiotic in the murine model of burn/Pseudomonas aeruginosa infected wound healing.

Methods & materials: Isolated and purified lytic bacteriophages from hospital sewage were added to the polyethylene glycol (PEG) based ointment. A second-degree burned wound on the back of twenty-four adult female mice was created. The wounds were infected subcutaneously with 100 μL of 1 × 10^2-3 CFU/mL P. aeruginosa. After 24 h, mice were randomly assigned to one of four groups: mice received a standard antibiotic (antibiotic-treated group), mice received an ointment without bacteriophage (PEG-based group), mice received a PEG-ointment with bacteriophage (bacteriophage-treated group), or mice received no treatment (untreated-control group). Every two days, the contraction of burned wounds, physical activity, and rectal body temperature were recorded. On day 10, mice were sacrificed, and the wounds were cut off and evaluated histopathologically.

Results: In ointments containing PEG, bacteriophages were active and stable. The mice receiving bacteriophage and PEG-based ointment had substantially different wound contraction in primary wound healing (P = 0.001). When compared to the control group, the bacteriophage-treated group showed significant variations in wound contraction (P = 0.001). The wound contraction changed significantly between the antibiotic and PEG-based groups (P = 0.002). In all groups, physical activity in mice improved over time, with significant differences (P = 0.001). When the 8th day was compared to the days 2, 4, and 6, significant changes were found (P = 0.001, P = 0.02, and P = 0.02, respectively). Both the positive control and bacteriophage-treated groups showed perfect wound healing histopathologically. However, no significant variations in microscopic histopathological criteria were found between the groups.

Conclusion: Formulated phage ointment could be a promising approach for treating infected burn wounds infected by P. aeruginosa in mice with no allergic reactions.

Keywords: Bacteriophage; Burned wounds; Mice; Ointment; Polyethylene glycol; Pseudomonas aeruginosa.