Zi Ye

A self-defensive antibacterial coating acting through the bacteria-triggered release of a hydrophobic antibiotic from layer-by-layer films

Drug delivery systems play important roles in the construction of antibacterial coatings on the surfaces of biomaterials. However, excessive release of antibiotics in the environment can lead to the generation of resistant bacteria. A methoxy poly(ethylene glycol)-poly(ε-caprolactone)-chitosan (MPEG-PCL-CS) block polymer was prepared through covalent grafting of CS onto MPEG-PCL. MPEG-PCL-CS micelles were prepared and showed a high load capacity for the hydrophobic antibiotic triclosan (TCA) (∼5 wt%). Multilayer films were constructed through self-assembling TCA/MPEG-PCL-CS cationic micelles with poly(acrylic acid) (PAA). Transmission and scanning electron microscopy analyses confirmed the presence of micelles on the surface (20-40 nm). As barriers for the antibiotic, the (TCA/MPEG-PCL-CS)/PAA multilayer films contained a high load of TCA (255 μg cm-2). Importantly, the multilayer films showed both bacteria-triggered and pH-responsive release properties and can be used as self-defensive antibacterial coatings. Bacterial adhesion caused a local acidic environment and altered the permeability of the multilayer films, promoting drug release. Both in vitro and in vivo antibacterial tests indicated a high bactericidal activity of drug-loaded multilayer films against both E. coli and S. aureus.

Surface-Adaptive Gold Nanoparticles with Effective Adherence and Enhanced Photothermal Ablation of Methicillin-Resistant Staphylococcus aureus Biofilm

Biofilms that contribute to the persistent bacterial infections pose serious threats to global public health, mainly due to their resistance to antibiotics penetration and escaping innate immune attacks by phagocytes. Here, we report a kind of surface-adaptive gold nanoparticles (AuNPs) exhibiting (1) a self-adaptive target to the acidic microenvironment of biofilm, (2) an enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus (MRSA) biofilm under near-infrared (NIR) light irradiation, and (3) no damage to the healthy tissues around the biofilm. Originally, AuNPs were readily prepared by surface modification with pH-responsive mixed charged zwitterionic self-assembled monolayers consisting of weak electrolytic 11-mercaptoundecanoic acid (HS-C10-COOH) and strong electrolytic (10-mercaptodecyl)trimethylammonium bromide (HS-C10-N4). The mixed charged zwitterion-modified AuNPs showed fast pH-responsive transition from negative charge to positive charge, which enabled the AuNPs to disperse well in healthy tissues (pH ∼7.4), while quickly presenting strong adherence to negatively charged bacteria surfaces in MRSA biofilm (pH ∼5.5). Simultaneous AuNP aggregation within the MRSA biofilm enhanced the photothermal ablation of MRSA biofilm under NIR light irradiation. The surrounding healthy tissues showed no damage because the dispersed AuNPs had no photothermal effect under NIR light. In view of the above advantages as well as the straightforward preparation, AuNPs developed in this work may find potential applications as a useful antibacterial agent in the areas of healthcare.

Direct Loading and Tunable Release of Antibiotics from Polyelectrolyte Multilayers To Reduce Bacterial Adhesion and Biofilm Formation.

Bacteria adhesion on the surface of biomaterials and following biofilm formation are important problems in biomedical applications. The charged antibiotics with small molar mass can hardly deposit alternately with polymers into multilayered films to load the drug. Herein, the (poly(acrylic acid)-gentamicin/poly(ethylenimine))n ((PAA-GS/PEI)n) multilayer film was designed and constructed via a layer-by-layer self-assembly method. Low molar mass GS cations were first combined with polyanion PAA and self-assembled with PEI to form multilayer films showing exponential growth behavior. The GS dosage could be adjusted by changing the layer number of films. Furthermore, the thermal cross-linking method was used to control the release rate of GS in PBS buffer. Owing to the diffusion of GS, a zone of inhibition of about 7.0 mm showed the efficient disinfection activity of the multilayer film. It could also be seen from the biofilm inhibition assay that the multilayer film effectively inhibited bacterial adhesion and biofilm formation. As the drug loading dosage was 160 μg/cm(2), the multilayer films showed very low cytotoxicity against human lens epithelial cells. The present work provides an easy way to load GS into multilayer films which can be applied to surface modification of implants and biomedical devices.

Construction of a temperature-responsive terpolymer coating with recyclable bactericidal and self-cleaning antimicrobial properties

Once a biomedical implant is implanted into a human body, proteins and bacteria can easily colonize the implant, and subsequently, a biofilm can grow on the surface. A biofilm can protect the inhabiting bacteria against macrophages and neutrophil cell attack from the host immune system. The most important issue for artificial antibacterial surfaces is the accumulation of the bacteria corpse after they are killed by contact, which promotes further adhesion of bacteria and biofilm formation. Therefore, we constructed a novel multifunctional bactericidal and fouling release antibacterial surface through the combination of temperature-responsive N-vinylcaprolactam (VCL), hydrophilic 2-methacryloyloxyethyl phosphorylcholine (MPC) and a bactericidal quaternary ammonium salt (2-(dimethylamino)-ethyl methacrylate (DMAEMA+)). The terpolymer coating was prepared through surface-initiated reversible addition-fragmentation chain-transfer (RAFT) polymerization and characterized using water contact angle measurements, atomic force microscopy and spectroscopic ellipsometry. At a temperature above the lower critical solution temperature (LCST), the P(VCL-co-DMAEMA+-co-MPC) terpolymer coating was in a compressed and hydrophobic state with low moisture content, which displayed bactericidal efficiency against Gram-positive Staphylococcus aureus. The coating could be switched into a relatively hydrophilic surface at a temperature below the LCST, which showed self-cleaning properties against both bacteria and bovine serum albumin. The functionalized surface showed good biocompatibility against human lens epithelial cells as evaluated by morphology studies and activity measurements.

Fabrication of nonfouling, bactericidal, and bacteria corpse release multifunctional surface through surface-initiated RAFT polymerization

Infections after surgery or endophthalmitis are potentially blinding complications caused by bacterial adhesion and subsequent biofilm formation on the intraocular lens. Neither single-function anti-adhesion surface nor contacting killing surface can exhibit ideal antibacterial function. In this work, a novel (2-(dimethylamino)-ethyl methacrylate-co-2-methacryloyloxyethyl phosphorylcholine) (p (DMAEMA-co-MPC)) brush was synthesized by “grafting from” method through reversible–addition fragmentation chain transfer polymerization. 1-Bromoheptane was used to quaternize the p (DMAEMA-co-MPC) brush coating and to endow the surface with bactericidal function. The success of the surface functionalization was confirmed by atomic force microscopy, water contact angle, and spectroscopic ellipsometry. The quaternary ammonium salt units were employed as efficient disinfection that can eliminate bacteria through contact killing, whereas the 2-methacryloyloxyethyl phosphorylcholine units were introduced to suppress unwanted nonspecific adsorption. The functionalized poly(dimethyl siloxane) surfaces showed efficiency in reducing bovine serum albumin adsorption and in inhibiting bacteria adhesion and biofilm formation. The copolymer brushes also demonstrated excellent bactericidal function against gram-positive (Staphylococcus aureus) bacteria measured by bacteria live/dead staining and shake-flask culture methods. The surface biocompatibility was evaluated by morphology and activity measurement with human lens epithelial cells in vitro. The achievement of the p (DMAEMA+-co-MPC) copolymer brush coating with nonfouling, bactericidal, and bacteria corpse release properties can be used to modify intraocular lenses.

Antimicrobial efficiency of PAA/(PVP/CHI) erodible polysaccharide multilayer through loading and controlled release of antibiotics

The adhesion of bacteria and subsequent formation of biofilm on the surface of implants greatly affect the long-term use of the implants. The low molar mass gentamicin (GS) cations could hardly be directly incorporated into the multilayer films through alternately deposition with a polyanion. Herein, we have designed and constructed a (poly(acrylic acid)/(polyvinylpyrrolidone/chitosan))n ((PAA/(PVP/CHI))n) multilayer films through layer-by-layer self-assembly method. Through increasing the pH to destroy hydrogen bonding between PAA and PVP, PVP released into the solution and GS simultaneously combined with PAA through electrostatic interactions. The loading dosage of GS into the (PAA/(PVP/CHI))10 multilayer film was up to 153.84±18.64μg/cm2 and could be precisely tuned through changing the thickness of the films. The release behaviour of GS in phosphate buffer saline could also be regulated through thermal cross-linking of the films. The drug-loaded multilayer films displayed efficient against three kinds of Gram-positive and three kinds of Gram-negative bacteria and one kind of fungi, and good biocompatibility towards human lens epithelial cells. GS-loaded multilayer films-coated polydimethylsiloxane (PDMS) were compared with pristine PDMS in the rabbit subcutaneous S. aureus infection model. The antimicrobial-coated implants yielded a much lower degree of infections than pristine implants at day seven.

Bacterial infection microenvironment-responsive enzymatically degradable multilayer films for multifunctional antibacterial properties

The adhesion of bacteria is one of the most important stages in biofilm formation and bacterial infection. Once bacteria have adhered to a biomaterial surface, it is hard to eliminate them, and bacterial growth and infection are inevitable. In the current study, we have designed and constructed enzymatically degradable (hyaluronic acid/chitosan)n-(hyaluronic acid/polylysine)n ((HA/CHI)n-(HA/PLL)n) composite multilayer films via a layer-by-layer self-assembly method. Spectroscopic ellipsometry and scanning electron microscopy cross section measurements showed the exponential growth behavior of (HA/CHI)10-(HA/PLL)10 multilayer films (∼2 μm). The increased secretion of hyaluronidase and chymotrypsin in the bacterial infection microenvironment led to the fast degradation of the outer (PLL/HA)n multilayer films in the first 24 h. Enzymatic degradation of the multilayer films efficiently reduced the adhesion of both Staphylococcus aureus and Escherichia coli (>99%). Bacterial live/dead staining demonstrated the bactericidal action of the remaining bottom (CHI/HA)n multilayer films against the two kinds of bacteria. In vivo subcutaneous tests on New Zealand white rabbits, wound appearance and histopathology analysis showed that the implantation of composite multilayer film-modified PDMS promoted wound healing and the materials demonstrated a self-defense antibacterial effect. The material demonstrated both anti-adhesive and bactericidal properties and could be used to modify biomedical implants.

Synthesis of chitosan-based micelles for pH responsive drug release and antibacterial application

The over- and inefficient release of antibiotics from common delivery systems causes the development of drug-resistant bacteria. In the present work, methoxy poly(ethylene glycol)-poly(ε-caprolactone)-chitosan/montmorillonite (MPC/MMT) hybrid multilayer films were constructed for bacterial infections and pH-dependent release of the hydrophobic drug triclosan (TCA). The thickness of the (MPC-T/MMT)10 multilayer films was 384.4 ± 26.5 nm, and the TCA loading dosage was 2.4 μg/cm2. Staphylococcus aureus, Escherichia coli and Staphylococcus epidermidis were used in the antibacterial tests. pH responsive TCA release from the prepared multilayer films was examined by measuring the bactericidal activity of the films after immersion in PBS (pH 7.4) or MES (pH 5.5) and zone of inhibition on nutrient agar. In vitro bacterial shake-flask, zone of inhibition and live/dead staining results demonstrated the high sterilization efficiency of the films. Furthermore, cell biocompatibility measurements toward L929 fibroblasts and human lens epithelial cells showed no adverse effects of the multilayer film.