Nanogels: A novel approach in antimicrobial delivery systems and antimicrobial coatings

Abstract

The implementation of nanotechnology to develop efficient antimicrobial systems has a significant impact on the prospects of the biomedical field. Nanogels are soft polymeric particles with an internally cross-linked structure, which behave as hydrogels and can be reversibly hydrated/dehydrated (swollen/shrunken) by the dispersing solvent and external stimuli. Their excellent properties, such as biocompatibility, colloidal stability, high water content, desirable mechanical properties, tunable chemical functionalities, and interior gel-like network for the incorporation of biomolecules, make them fascinating in the field of biological/biomedical applications. In this review, various approaches will be discussed and compared to the newly developed nanogel technology in terms of efficiency and applicability for determining their potential role in combating infections in the biomedical area including implant-associated infections.

Keywords: Antibacterial activity; Antifouling; Biocompatibility; Coatings; Nanogels.

Graphical abstract

Scheme 1

Schematic representation of the different strategies of nanogel design and their applications in biomedical field.

Fig. 1

Schematic description of nanogel formation by heterogeneous polymerization. The inverse emulsion, inverse miniemulsion and inverse microemulsion polymerization are considered to proceed as follows: (a) emulsification and homogenization, (b) polymerization, (c) removal of excess surfactant, and (d) transfer to good solvent. The dispersion and precipitation polymerization are considered to proceed as follows: (e) initiation and chain growth, (f) precipitation and nucleation by polymer chains collapse when the temperature is far above the lower critical solution temperature or by colloidal stabilizer on the surface of the unstable particles, (g) particle growth and (h) transfer to good solvent or decrease of temperature below the volume phase transition temperature.

Fig. 2

Microgel coatings reduce chronic inflammation associated with materials implanted subcutaneously in the rat dorsum for 4 wk. Explants were evaluated for fibrous encapsulation by staining collagen (pink), elastin (black), and nuclei (black). Representative images for unmodified PET (a) and microgel-coated PET (b) disks, and the original implant location is designated. Black arrows indicate capsule measurements. Microgel coatings reduced fibrous capsule thickness by 22% compared to unmodified PET controls as quantified in (c), *p < 0.04. The density of capsule-associated cells was also significantly reduced in microgel-coated samples (*p < 5.6 × 10−3) compared to unmodified PET controls as quantified in (d). Data is represented as the average value ± standard error of the mean using n = 4–7 samples per treatment group. Scale bar is 50 μm. (Reproduced with permission from ref 144. (Copyright 2010 Wiley).

Fig. 3

(A) Schematic illustration of a vancomycin‐loaded mannosylated nanogels (MNG‐V) and the bacteria‐responsive drug release; (B) Schematic illustration of targeted uptake of MNG‐V, transport, degradation, drug release and bacteria inhibition. (Reproduced with permission from ref 192. (Copyright 2012 Wiley)).

Fig. 4

(a) Preparation of vancomycin encapsulated supramolecular gelatin nanoparticles with RBC membrane coating layer (Van⊂SGNPs@RBC). (b) Schematic representation of adaptive and multifunctional Van⊂SGNPs@RBC in the treatment of a bacterial infection. (Reproduced with permission from ref 193. (Copyright 2014 American Chemical Society)).

Fig. 5

Preparation of Ca²⁺-cross-linked alginate nanogels loaded with the AMP polymyxin B in a continuous process using 3D-printed micromixers with three different geometric designs: turbulent flow micromixers, laminar flow micromixers, or integrated compartment micromixers. (Reproduced with permission from ref 248. (Copyright 2019 Elsevier)).

Fig. 6

Schematic presentation of the fabrication of PNG by coordination-assisted self-assembly of a mannose-conjugated antimicrobial polypeptide, poly (arginine-r-valine)-mannose with Zn²⁺ ions. (Reproduced with permission from ref 258. (Copyright 2019 American Chemical Society)).

Fig. 7

Atomic force microscopy images of the p (NIPMAM) nanogel coated glass surfaces with different internal stiffness/cross-linking density and hydrodynamic radii R_h at 23 °C in the dry state. (A) nGel1, R_h = 114 nm, (B) nGel2, R_h = 109 nm, (C) nGel3, R_h = 101 nm, (D) nGel4, R_h = 787 nm, (E) nGel5, R_h = 301 nm, (F) nGel6, R_h = 650 nm at 30 °C. (Reproduced with permission from ref 29. (Copyright 2019 American Chemical Society)).

Fig. 8

Fabrication diagram of the pH-responsive membrane prepared with nanogels. (Reproduced with permission from ref 285. (Copyright 2019 Elsevier)).

Fig. 9

Integrated antibacterial and antifouling membranes via cross-linking eugenol-modified chitosan and a zwitterionic copolymer on the electrospun polyurethane surface. (Reproduced with permission from ref 288. (Copyright 2018 Elsevier)).

Fig. 10

(A) Bacterial adhesion of E. coli to surface-modified glass slides after 4 h of incubation in Tris buffer with or without additional 150 mM NaCl (top) and viability of the adhered E. coli quantified using BacLight LIVE/DEAD staining (bottom). Data were normalized against E. coli killed in 70% isopropanol. (B) Representative CLSM images of adhered E. coli on surface-modified glass slides in 10 mM Tris buffer. Images are presented as z-projections of stacks of six images or more, with increased brightness and contrast added after data analyses for improved visualization. (Reproduced with permission from ref 290. (Copyright 2018 American Chemical Society)).

Fig. 11

Schematic representation of antifouling and antimicrobial nanogel coatings (Reproduced with permission from ref 297. (Copyright 2019 Elsevier)).

Fig. 12

Contact transfer kills S. epidermidis on AMP loaded microgel-modified surfaces. Confocal images showing live (green) and dead (red) S. epidermidis after 30 min of contact with microgels loaded with: (A) Antimicrobial peptide L5 (in 0.07 M ionic strength buffer); and (B) Antimicrobial peptide Sub5 (in 0.28 M ionic strength buffer). The dashed lines outline the outer diameter of the probe tip. (Reproduced with permission from ref 305. (Copyright 2019 Elsevier)).