Polymer Multilayers with pH-Triggered Release of Antibacterial Agents

Abstract

We report on the layer-by-layer design principles of poly(methacrylic acid) (PMAA) ultrathin hydrogel coatings that release antimicrobial agents (AmAs) in response to pH variations. The studied AmAs include gentamicin and an antibacterial cationic peptide L5. Adipic acid dihydrazide (AADH) is a cross-linker which, relative to ethylenediamine (EDA), increases the hydrogel hydrophobicity and introduces centers for hydrogen bonding to AmAs. AmA retention in AADH-cross-linked hydrogels in high-salt solutions was enhanced while AmA release at low pH was suppressed. L5 retains its antibacterial activity toward planktonic Staphylococcus epidermidis after release from PMAA hydrogels in response to pH decreases in the surrounding medium due to bacterial growth. Staphylococcus epidermidis adhesion and colonization was almost completely inhibited by L5 loading of hydrogels. The AmA-releasing and AmA-retaining properties of these hydrogel coatings provide new opportunities to study the fundamental mechanisms of AmA-coating-bacteria interactions and develop a new class of clinically relevant antibacterial coatings for medical devices.

Small-molecule-hosting nanocomposite films with multiple bacteria-triggered responses

“…This suggests that release is determined by the charge balance of gentamicin ionic pairing with PAA units within the film and occurs as ionic pairing is disrupted because of the protonation of PAA in low-pH solutions. In contrast to our previously reported single-component films of all-polymer chemically crosslinked poly(methacrylic acid) LbL hydrogels, 26 clay/PAA layers exhibit significantly enhanced retention of antibiotics within the host matrix in salt solutions, most likely because of favorable dipole-dipole interactions of antibiotics with MMT nanoplatelets. Increasingly, large percentages of gentamicin were released from MMT/PAA films in solutions with lower pH, as confirmed by FTIR and AFM (Figures 4a and b).…”

“…23,24 Moreover, antibacterial surfaces have been designed that can respond to light or pH. 25,26 The present study goes beyond this prior work by describing a new type of coating that was engineered to combine permanent, contactkilling protection with bacteria-triggered, on-demand release of antimicrobials. By exploring clay-containing nanocomposites rather than all-polymer films as matrices to host an antibiotic, we were able to prevent low-level tail release of antibiotics that consequently minimizes the development of antibiotic resistance.…”

“…By exploring clay-containing nanocomposites rather than all-polymer films as matrices to host an antibiotic, we were able to prevent low-level tail release of antibiotics that consequently minimizes the development of antibiotic resistance. Simultaneously, we combined antibiotic retention with a bacteria-triggered release mechanism, a concept recently introduced by our group, 26,27 such that antimicrobials remain sequestered within coatings until bacteria approach the surface. In our model, the secretion of lactic acid by staphylococci 28 or acetic acid by Escherichia coli 29 locally acidifies the environment to induce a pH-triggered release of antibiotics.…”

“…30 Although we have previously demonstrated the concept of 'self-defense' antibacterial protection using a strongly charged, toxic peptide, a clinically relevant cationic antibiotic for local release, such as gentamicin, could not be sufficiently retained within all-polymer gel films and microgels in 0.2 M salt solutions at pH 7.5. 26 Here, by using a clay-polymer nanocomposite matrix, we were able to achieve a combination of strong antibiotic retention with bacteria-triggered release under physiologic conditions.…”

Development of fibroblast culture in three-dimensional activated carbon fiber-based scaffold for wound healing

“…It was known that gentamicin is a commonly used antibiotic agent due to its broad antibacterial spectrum of action [24]. Junge et al [25] have demonstrated that gentamicin modification of a polyvinylidenfluoride mesh induces increased expression of type I collagen mRNA and decreased expression of collagenases (MMP-8 and MMP-13), and consequently, an increased type I collagen ratio at the mesh/host tissue interface.…”