Chitosan-Based Microparticle Encapsulated Acinetobacter baumannii Phage Cocktail in Hydrogel Matrix for the Management of Multidrug Resistant Chronic Wound Infection

Objectives: Multi-drug resistant bacteria have been implicated in various debilitating infections that have led to life loss. This study developed an approach to tackle multidrug resistant Acinetobacter baumannii infection in a chronic wound model through A. baumannii phage encapsulation with resuspension in hydrogel. Materials and Methods: Two isolates of A. baumannii-specific lytic phases phi AB140 and phi AB150 alone, in combination (cocktail) encapsulated within a chitosan (CS) microparticle was suspended in CS hydrogel and evaluated for their therapeutic efficacy to ensure bacterial clearance in A. baumannii induced diabetic wound infection. Microencapsulation of the phage was carried out using ionic gelation techniques Biological characterization via cell cytoxicity, in vivo wound healing, histology and histomorphometry was carried out. Results: Two characterized A. baumannii phages (phi AB140 and phi AB150), specific to twenty A. baumannii isolates, were isolated. The encapsulated CS microparticle hydrogel exhibited a pH of 5.77 +/- 0.05. The wound size reduction was most pronounced in formulation C2, which showed statistically significant wound seize reduction on days 4 and 7, 56.79 +/- 2.02% and 62.15 +/- 5.11%, respectively. The optimized concentration of C2 was not toxic to the cells as it adequately supported cell growth with a proliferation rate of 215 +/- 7.89% compared to control (107.32 +/- 4.55%). Conclusion: Microparticle carrier technology was used to show the lytic activity against multi drug-resistant A. baumannii. In vivo results showed significant wound size reduction that was most pronounced in formulation C2 on day 4.