Alginate-caseinate based pH-responsive nano-coacervates to combat resistant bacterial biofilms in oral cavity

Biofilm associated microbial resistance is a major concern in oral health and hygiene. Nano-antimicrobials (NAMs) having natural antibiotic replacers e.g. nisin are the possible solution to treat oral infections. In this study, we have developed pH responsive, mucoadhesive protein-polysaccharide [sodium caseinate (NaC)-sodium alginate (AL)] coacervate based nano-carrier systems (PPC-NCS) to prevent and eradicate oral biofilms associated pathogens e.g. Enterococcus faecium, Staphylococcus epidermidis and Enterococcus faecalis. PPC-NCS were formed at pH 5 with highest encapsulation efficiency of 75.1 ± 1.2%, then at pH 6 (31 ± 1.1%) and 7 (15 ± 2%). SEM of PPC-NCS displayed smooth and round morphology. Particle size of PPC-NCS was observed to be 244 nm by DLS, with negative zeta potential (-47 ± 4.31 mV). In FTIR analysis, merging of OH stretching peak of NaC (2889.53 cm^-1) and CH stretching of AL (2920 cm^-1) with appearance of a new peak at 2062 cm^-1 was observed that confirmed covalent and hydrogen bonding between two compounds. Antimicrobial and antibiofilm assays demonstrated better control of nisin loaded PPC-NCS against selected pathogens, while preventing and eradicating bacterial biofilms successfully without any cytotoxic effect. These results recommend that coacervates based NAMs are suitable carriers for pH-triggered release of antimicrobials in the buccal cavity to control biofilm associated oral infections.