Layer-by-Layer (LBL) Self-Assembled Biohybrid Nanomaterials for Efficient Antibacterial Applications

Abstract

Although antibiotics have been widely used in clinical applications to treat pathogenic infections at present, the problem of drug-resistance associated with abuse of antibiotics is becoming a potential threat to human beings. We report a biohybrid nanomaterial consisting of antibiotics, enzyme, polymers, hyaluronic acid (HA), and mesoporous silica nanoparticles (MSNs), which exhibits efficient in vitro and in vivo antibacterial activity with good biocompatibility and negligible hemolytic side effect. Herein, biocompatible layer-by-layer (LBL) coated MSNs are designed and crafted to release encapsulated antibiotics, e.g., amoxicillin (AMO), upon triggering with hyaluronidase, produced by various pathogenic Staphylococcus aureus (S. aureus). The LBL coating process comprises lysozyme (Lys), HA, and 1,2-ethanediamine (EDA)-modified polyglycerol methacrylate (PGMA). The Lys and cationic polymers provided multivalent interactions between MSN-Lys-HA-PGMA and bacterial membrane and accordingly immobilized the nanoparticles to facilitate the synergistic effect of these antibacterial agents. Loading process was characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and X-ray diffraction spectroscopy (XRD). The minimal inhibition concentration (MIC) of MSN-Lys-HA-PGMA treated to antibiotic resistant bacteria is much lower than that of isodose Lys and AMO. Especially, MSN-Lys-HA-PGMA exhibited good inhibition for pathogens in bacteria-infected wounds in vivo. Therefore, this type of new biohybrid nanomaterials showed great potential as novel antibacterial agents.

Controlling release kinetics of gentamicin from silica nano-carriers

“…Despite the excellent blood compatibility and low toxicity demonstrated by these nanocarriers [62], the release was sustained for about 1 week; hence not as effective as the nanocarriers presented in this work. LbL has also been used to prepare antibiotic loaded silica nanocarriers [63], [64]. This approach was employed to entrap the drug under polyelectrolytes that enhance bacterial cell penetration [64] or to seal the drug inside mesoporous particles and, therefore, the polyelectrolytes acted as "gatekeeper" [49]; in this way sustained the release for about 10 days was achieved [63]; again not as effective as the nanocarriers presented in this work.…”

Smart Delivery Systems Based on Poly(glycidyl methacrylate)s‐Coated Organic/Inorganic Core–Shell Nanohybrids

“…Subsequently, for efficient antisepsis, Yang and Gao et al constructed a biohybrid nanomaterial by coating lysozyme (Lys), hyaluronic acid, and PGEDA on MSNs surface via LbL approach . Due to the multivalent interactions between Lys/cationic polymers and bacterial membrane, these nanoparticles were immobilized to synergistically enhance the effect of antibacterial agents.…”

Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper–Hollow Silica Nanoparticles

“…Furthermore, combination therapy generally requires multiple injections, which may compromise patient compliance and complicate the therapy process. Therefore, sequential delivery of multiple drugs to the target site would be desirable for improving the efficacy of combination chemotherapy13141516.…”