Antimicrobial hydrogels: promising materials for medical application

Abstract

The rapid emergence of antibiotic resistance in pathogenic microbes is becoming an imminent global public health problem. Local application of antibiotics might be a solution. In local application, materials need to act as the drug delivery system. The drug delivery system should be biodegradable and prolonged antibacterial effect should be provided to satisfy clinical demand. Hydrogel is a promising material for local antibacterial application. Hydrogel refers to a kind of biomaterial synthesized by a water-soluble natural polymer or a synthesized polymer, which turns into gel according to the change in different signals such as temperature, ionic strength, pH, ultraviolet exposure etc. Because of its high hydrophilicity, unique three-dimensional network, fine biocompatibility and cell adhesion, hydrogel is one of the suitable biomaterials for drug delivery in antimicrobial areas. In this review, studies from the past 5 years were reviewed, and several types of antimicrobial hydrogels according to different ingredients, different preparations, different antimicrobial mechanisms, different antimicrobial agents they contained and different applications, were summarized. The hydrogels loaded with metal nanoparticles as a potential method to solve antibiotic resistance were highlighted. Finally, future prospects of development and application of antimicrobial hydrogels are suggested.

Keywords: antibiotics; drug delivery; hydrogels; infection; nanomaterials; nanoparticles.

Figure 1

The different applications of hydrogels.

Figure 2

Transmission electron microscope image of Escherichia coli cells treated with silver nanoparticles in liquid Luria-Bertani medium: (A) membrane of E. coli; (B) nanoparticles accumulated in the membrane and penetrated the cell (arrows). Note: Reprinted from Adv Drug Deliv Rev. 65(13–14). Pelgrift RY, Friedman AJ, Nanotechnology as a therapeutic tool to combat microbial resistance1803–1815, Copyright (2013), with permission from Elsevier.

Figure 3

Gao et al synthesized hydrogel containing Au NP-stabilized liposomes for antimicrobial application (A) illustrations of hydrogel containing nanoparticle-stabilized liposomes for topical antimicrobial delivery; (B) bacteria incubated with AuC–liposome hydrogel (PEGDMA 0.8 vol%) at pH = 4.5; (C) a zoomed-in image of (B). Note: The scale bars in (B and C) represent 1 µm. Reproduced from Gao W, Vecchio D, Li J, et al. Hydrogel containing nanoparticle-stabilized liposomes for topical antimicrobial delivery. ACS Nano. 2014;8(3):2900–2907.

Figure 4

Multiple mechanisms of antimicrobial action of Ag NPs, ZnO NPs, copper-containing nanoparticles and Mg NPs are separately exhibited. Note: Reprinted from Adv Colloid Interface Sci. 166(1–2). Dallas P, Sharma VK, Zboril R, Silver polymeric nanocomposites as advanced antimicrobial agents: classification, synthetic paths, appli cations, and perspectives, 119–135, Copyright 2011, with permission from Elsevier.³⁷ Abbreviations: Ag NPs, silver nanoparticles; Mg NPs, magnesium-containing nanoparticles; NP, nanoparticle; ROS, reactive oxygen species; UV, ultraviolet; ZnO NPs, zinc oxide nanoparticles.

Figure 5

Development of antibiotics and appearance of drug resistance are summarized chronologically referring to Huh and Kwon, Andersson and Hughes, Rodriguez- Rojas et al, van Hoek et al, Molton et al.¹³⁵ Abbreviations: E. coli, Escherichia coli; K. pneumoniae, Klebsiella pneumoniae; MRSA, methicillin resistant S. aureus; S. aureus, Staphylococcus aureus; VISA, vancomycin intermedicate resistant S. auereus; VRE, vancomycin-resistant Enterococcus; VRSA, vancomycin-resistant S. aureus.

Figure 6

Mode of action for intracellular antimicrobial peptide activity. In this figure Escherichia coli was shown as the target microorganism from Brogden. Note: Reprinted by permission from Springer Nature, Nat Rev Microbiol, Brogden KA, Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? 2005;3(3): 238–250, Copyright 2005.

Figure 7

Morphological observation of various microorganisms seeded on hydrogels by scanning electron microscope. Left columns (control), right columns (antimicrobial hydrogels). Note: Reprinted from Biomaterials. 32(11). Zhou C, Li P, Qi X, et al, A photopolymerized antimicrobial hydrogel coating derived from epsilon-poly-l-lysine, 2704–2712, Copyright 2011, with permission from Elsevier.²⁴² Abbreviations: C. albicans, Candida albicans; E. coli, Escherichia coli; F. solani, Fusarium solani; P. aeruginosa, Pseudomonas aeruginosa; S.aureus, Staphylococcus aureus; S. marcescens, Serratia marcescens.

Figure 8

A new strategy that uses catecholic chemistry to synthesize antimicrobial silver nanoparticles impregnated into antifouling zwitterionic hydrogels. Notes: On the top is the schematic illustration of the combination of AgNPs and antifouling hydrogel. In the middle, Photographs show the changes in color of hydrogels by changing the pH because of reaction that converts the Ag+ into solid AgNPs. The bottom section shows the surface structure and the morphology of hydrogel via scanning electron microscopy. Reprinted with permission from GhavamiNejad A, Park CH, Kim CS. In situ synthesis of antimicrobial silver nanoparticles within antifouling zwitterionic hydrogels by catecholic redox chemistry for wound healing application. Biomacromolecules. 2016;17(3):1213–1223. Copyright (2016), American Chemical Society.

Figure 9

Graphical representation of MICs obtained after growing S. aureus and P. aeruginosa in the presence of different concentrations of gentamicin and ZnO/gentamicin–chitosan. Note: Reprinted from Int J Pharm. 463(2). Vasile BS, Oprea O, Voicu G, et al, Synthesis and characterization of a novel controlled release zinc oxide/gentamicin-chitosan composite with potential applications in wounds care, 161–169, Copyright 2014, with permission from Elsevier. Abbreviations: MICs, minimal inhibition concentrations; S. aureus, Staphylococcus aureus; P. aeruginosa, Pseudomonas aeruginosa.