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

Abstract

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 therapeutic platform, capable of co-delivering Salmonella bacteriophage MET P1-001 and curcumin (CUR). First, LbL films consisting of alginate and poly[2-(diisopropylamino)ethyl methacrylate]-block-poly[3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate] (PDPA-b-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 Salmonella bacteriophages, but differently, PDPA-b-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 Salmonella enterica subsp. enterica serovar Enteritidis (Salmonella 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 Salmonella bacteriophage MET P1-001 and CUR using LbL technology, and the enhancement of antibacterial efficacy through co-delivery of these therapeutics.