Alginate–Chitosan Biopolymer Nanoparticles for Efficient Bacteriophage Encapsulation and Transport

Background/Objectives: The quest for effective therapeutic alternatives for infec-tions caused by multidrug-resistant (MDR) bacteria remains a major global health priority. In this context, bacteriophage therapy has re-emerged as a promising strate-gy due to its high host specificity and ability to infect and lyse targeted bacterial strains. However, clinical translation is limited by biological and technological chal-lenges, including phage instability and rapid inactivation after administration. Algi-nate- and chitosan-based polymeric nanomatrices offer a practical way to address these limitations. Properly engineered nanoparticles can improve phage stability, protect against environmental stressors, reduce inactivation, and enable localized, controlled release at the infection site. Methods: A polysaccharide-based nanocarrier composed of hydrophobically modified alginate (mAlg) and chitosan was developed. Encapsulation of bacteriophage vB_Eco_K-02 within mAlg-Cs nanoparticles was achieved by ultrasonication-assisted polyelectrolyte complexation. Particle size, ζP, and morphology were evaluated, and phage encapsulation efficiency and antibacte-rial activity were assessed in vitro. Results: The mAlg-Cs formulation at a 1:0.625 mass ratio yielded nanoparticles with the most favorable physicochemical properties, including improved size distribution, high colloidal stability, and regular morphology. vB_Eco_K-02-loaded NPs (mAlg-Cs-Phg) achieved a high encapsulation efficiency (99 %) and preserved lytic activity after formulation, resulting in strong inhibition of E. coli growth in kinetic assays. Conclusions: mAlg-Cs nanoparticles provide an effi-cient platform for encapsulating vB_Eco_K-02 while preserving phage infectivity and enabling effective antibacterial activity. This nanosystem represents a promising strategy to enhance phage delivery for the treatment of bacterial infection.