Targeted Release of Tobramycin from a pH-Responsive Grafted Bilayer Challenged with S. aureus

Abstract

A stimuli-responsive, controlled release bilayer for the prevention of bacterial infection on biomaterials is presented. Drug release is locally controlled by the pH-responsiveness of the bilayer, comprised of an inner poly(acrylic acid) (PAA) monolayer grafted to a biomaterial and cross-linked with an outer chitosan (CH) brush. Tobramycin (TOB) is loaded in the inner PAA in part to minimize bacteria resistance. Because biofilm formation causes a decrease in local pH, TOB is released from PAA and permeates through the CH which is in contact with the biofilm. Antibiotic capacity is controlled by the PAA thickness which depends on PAA brush length and the extent of cross-linking between CH and PAA at the bilayer interface. This TOB-loaded, pH responsive bilayer exhibits significantly enhanced antibacterial activity relative to controls.

Responsive and Synergistic Antibacterial Coatings: Fighting against Bacteria in a Smart and Effective Way

“…In addition to LBL multilayered coatings, there are some other pH‐responsive antibacterial coatings containing negatively charged polymers with the same mechanism of bacteria‐triggered release of antibiotics with positive charge . For example, a multifunctional grafted PAA/chitosan bilayer was developed as a pH‐responsive reservoir for storage and on‐demand release of antibiotics.…”

“…For example, a multifunctional grafted PAA/chitosan bilayer was developed as a pH‐responsive reservoir for storage and on‐demand release of antibiotics. [28a] The inner PAA layer was loaded with the cationic antibiotic tobramycin (TOB) via electrostatic interaction and cross‐linked with the outer chitosan layer. As for the process of bacteria colonization and biofilm formation, the localized acidification near the infected area caused the reduction of electrostatic attraction between PAA and TOB as well as hydration and swelling of the chitosan layer, leading to the release of TOB that permeates through the bilayer and kills bacteria and eliminates biofilms.…”

Multifunctional biomaterial coatings: synthetic challenges and biological activity

“…Beyond that, specific peptide sequences can feature anti-microbial activity (Peyre et al, 2012;Krizsan et al, 2014). Classic and novel antibiotic reagents are mostly used through a release mechanism to circumvent infections of biomaterials (Fullenkamp et al, 2012;Lee et al, 2015).…”

Layer-by-layer assemblies for antibacterial applications

“…30 Silver ions were also loaded into synthetic nanogels consisting of chitosan and subsequently in situ reduced to silver nanoparticles. 43 In general, charged antibiotics or charged antibiotic carriers can be easily incorporated into LbL assemblies because of electrostatic interactions and subsequently be released to kill bacteria. 3.…”