Layer-by-Layer Coated Alginate Hydrogels with Antibacterial Activity Based on Bacteriophage and Curcumin Combination.

There is a need to develop alternative antibacterial agents for antibacterial applications due to the emergence of antibiotic-resistant bacteria. Bacteriophages are natural predators of bacteria and have gained interest as an alternative to antibiotics. The co-delivery of antibacterial agents is an attractive strategy to achieve enhanced antibacterial activity. This study investigated the use of layer-by-layer (LbL) technology to functionalize alginate hydrogels to prepare a platform, capable of co-delivering bacteriophage MET P1-001 and curcumin (CUR). First, LbL films consisting of alginate and poly-[2-(diisopropylamino)-ethyl methacrylate]--poly-[3-dimethyl-(methacryloyloxyethyl)-ammonium propanesulfonate] (PDPA--βPDMA) micelles were prepared. Multilayers exhibited temperature-responsive behavior through upper critical solution temperature (UCST)-type phase behavior of polyzwitterionic βPDMA coronal chains. LbL assembly temperature affected the film thickness, and the post-assembly temperature was critical to the stability of multilayers against pH changes. Second, these multilayers were deposited on alginate hydrogels containing bacteriophages, but differently, PDPA--βPDMA micelles were loaded with CUR. CUR release from hydrogels was greater at pH 5.0 than at pH 7.0. Decreasing the release temperature did not make a considerable effect on the amount of CUR release at pH 7.0 but reduced its release at pH 5.0. The antibacterial activity against serovar Enteritidis ( Enteritidis) was mainly due to the release of bacteriophages from the hydrogel and was greater at pH 5.0 than at pH 7.0. Bacteriophages and CUR acted in a combinatorial manner at pH 7.0, while it was not statistically significant at pH 5.0. Overall, this study has generated fundamental knowledge on the preparation of alginate hydrogels co-delivering bacteriophage MET P1-001 and CUR using LbL technology, and the enhancement of antibacterial efficacy through co-delivery of these therapeutics.