Chemical grafting of antibiotics into multilayer films through Schiff base reaction for self-defensive response to bacterial infections

Abstract

Pathogenic bacteria can easily adhere to implanted biomaterials, and this is followed by rapid propagation and biofilm formation. In intravenous prophylactic administration and general topical administration based on physical or non-covalent bonding of antibiotics it is difficult to prevent low concentration release and excessive release, which lead to the development of drug-resistant bacteria. In this work, gentamicin sulfate (GS) was grafted onto aldylated sodium alginate (al-ALG) through dynamic chemical covalent bonding via a Schiff base reaction between aldehyde and amino groups. Antibiotic-loaded sodium alginate was coated on biomaterials by self-assembly with positively charged poly(ethyleneimine) (PEI) to form multilayer films. The ALG-GS/PEI multilayer films showed high antibiotic-loading capacities (223 μg/cm2) through dynamic chemical bonding. The release of GS gave bacterial infection self-defensive features. GS release was much faster at pH 5.5 than at pH 7.4. In vitro antibacterial tests, namely bacterial live/dead staining, zone of bacterial inhibition, and shake-flask culture methods showed efficient bactericidal activity with Staphylococcus aureus and Escherichia coli as model bacteria. ALG-GS/PEI multilayer films killed more than 99.99% of bacteria after 24 h incubation. These antibiotic-loaded multilayer films with long-term, self-defensive, smart bacterial infection and biofilm inhibition properties were almost totally resistant to biofilm development after 72 h incubation. The advantages of chemically grafting antibiotics are reflected in the maintenance of inhibition zone size after storage in a simulated body fluid environment. Dynamic chemical bonding of antibiotics in multilayer films has promising potential applications in biomaterial surface modification.