Bacteriophage-Loaded In-Situ Gel For Pseudomonas Aeruginosa Keratitis: An In Vivo Rabbit Model Study

To evaluate the therapeutic potential of a novel bacteriophage-loaded in-situ gelling formulation for the treatment of Pseudomonas aeruginosa keratitis in a rabbit model. The study aims to assess the formulation's antimicrobial efficacy, ocular retention, and impact on clinical and histopathological outcomes compared to conventional antibiotic treatment.

The study was conducted at an ophthalmic research laboratory in collaboration with microbiology and pharmaceutical sciences departments. The experimental model involved New Zealand white rabbits with induced P. aeruginosa keratitis, following institutional animal care and ethics guidelines.

A specific lytic bacteriophage (vB_Pa_ZCPS1) was isolated and incorporated into an in-situ gel composed of Pluronic F-127 and HPMC K4M. Forty rabbits were divided into four groups: uninfected controls, infected untreated controls, infected rabbits treated with imipenem/cilastatin, and infected rabbits treated with the bacteriophage gel. Treatment efficacy was assessed through clinical scores, corneal opacity, ulcer size, intraocular pressure measurements, and histopathological examination over a 12-day follow-up.

Rabbits treated with the bacteriophage-loaded gel demonstrated significant clinical improvement, with reduced corneal opacity and ulcer size compared to untreated controls. Histopathological analysis revealed intact corneal epithelium and reduced inflammation in the phage-treated group. Clinical scores were comparable between the bacteriophage and antibiotic groups, but phage therapy showed advantages in maintaining corneal architecture. No significant intraocular pressure changes were observed across groups.

Bacteriophage-loaded in-situ gel demonstrates promising potential as an alternative therapy for P. aeruginosa keratitis. The sustained release formulation enhances phage retention and efficacy, leading to improved clinical and histopathological outcomes. This novel approach offers a viable, antibiotic-sparing strategy for resistant bacterial keratitis, warranting further translational research and clinical evaluation.