International Journal of
Molecular Sciences
Review
Recent Advances in Antimicrobial Polymers:
A Mini-Review
Keng-Shiang Huang
1
, Chih-Hui Yang
2
, Shu-Ling Huang
3
, Cheng-You Chen
3
, Yuan-Yi Lu
3
and
Yung-Sheng Lin
3,
*
1
The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 84001, Taiwan;
huangks@isu.edu.tw
2
Department of Biological Science and Technology, I-Shou University, Kaohsiung 84001, Taiwan;
chyang@isu.edu.tw
3
Department of Chemical Engineering, National United University, Miaoli 36003, Taiwan;
simone@nuu.edu.tw (S.-L.H.); wayne20410@gmail.com (C.-Y.C.); ilovego0014010@yahoo.com.tw (Y.-Y.L.)
* Correspondence: linys@nuu.edu.tw; Tel.: +886-37-382-199
Academic Editors: Antonella Piozzi and Iolanda Francolini
Received: 21 July 2016; Accepted: 14 September 2016; Published: 20 September 2016
Abstract:
Human safety and well-being is threatened by microbes causing numerous infectious
diseases resulting in a large number of deaths every year. Despite substantial progress in antimicrobial
drugs, many infectious diseases remain difficult to treat. Antimicrobial polymers offer a promising
antimicrobial strategy for fighting pathogens and have received considerable attention in both
academic and industrial research. This mini-review presents the advances made in antimicrobial
polymers since 2013. Antimicrobial mechanisms exhibiting either passive or active action and
polymer material types containing bound or leaching antimicrobials are introduced. This article also
addresses the applications of these antimicrobial polymers in the medical, food, and textile industries.
Keywords: antimicrobial; polymer; microbe; bacteria; review
1. Introduction
Microbes are living organisms, such as bacteria, fungi, and parasites, which are the critical
sources of infections [
1
]. Infectious diseases result from pathogenic microbes and kill more people
than any other single cause [
2
]. An antimicrobial is an agent used to kill microbes or inhibit their
growth. Although numerous antimicrobial drugs have been developed to kill or inhibit microbes,
many infectious diseases remain difficult to treat [
3
,
4
]. Antimicrobial polymers were discovered since
1965 [
5
] and have attracted considerable attention in both academic and industrial research. Table 1
shows recent review articles on antimicrobial polymers from various perspectives. These reviews
focus on methods for producing antimicrobial polymers and various applications of antimicrobials.
Increasing efforts develops learning from nature, green or nontoxic biocides. The medical, food,
and textile industries are three major areas of applied antimicrobials. More than 27,845 patents for
antimicrobial polymers have been filed in the Google Patent Search database since 2013. In addition,
antimicrobial medical devices have attracted substantial attention in clinical trials [
5
]. Compared with
their small molecular counterparts, antimicrobial polymers demonstrate superior efficacy, reduced
toxicity, minimized environmental problems, and greater resistance [6].
Int. J. Mol. Sci. 2016, 17, 1578; doi:10.3390/ijms17091578 www.mdpi.com/journal/ijms
Int. J. Mol. Sci. 2016, 17, 1578 2 of 14
Table 1. Recent review articles of antimicrobial polymers.
Subject Topic Reference
Application
Stimuli-responsive polymeric materials for human health applications [
7]
Antimicrobial polymers for anti-biofilm medical devices [
8]
Antimicrobial peptides in the treatment of bacterial biofilm infections [
9]
Overview
Antimicrobial peptides and enzymes [10]
Anti-infectious surfaces achieved by polymer modification [
11]
Antimicrobial polymers [
6]
Antimicrobial polymers with metal nanoparticles [
12]
Synthesis and
characteristic
Antimicrobial N-halamine polymers and coatings [
13]
Antimicrobial modifications of polymers [
14]
Antibacterial dental resin composites [
15]
Novel formulations for antimicrobial peptides [
16]
Coatings and surface modifications imparting antimicrobial activity to orthopedic implants
[17]
Antimicrobial activity of chitosan derivatives containing n-quaternized moieties [
18]
Cationic polymers and their self-assembly for antibacterial applications. [
19]
Antimicrobial polymeric materials with quaternary ammonium and phosphonium salts [
20]
When microbes adhere to a substrate, they excrete biofilms to anchor themselves to the substrate.
In biofilms, cells grow in multicellular aggregates and become embedded within a self-produced
matrix of an extracellular polymeric substance. A biofilm extracellular polymeric substance is a
polymeric conglomeration composed of polysaccharides and other components, such as proteins and
DNA. Defective biofilms cannot offer an environment for microbes to grow. Therefore, antimicrobial
applications entail strategies for preventing microbial viability or adhesion. For example, antimicrobial
peptides act primarily by disrupting the bacterial cell membrane, and heparin exhibits anti-adhesive
activity and hydrophilic characteristics that prevent the growth of microbes [
21
]. Several reviews have
described antimicrobial management [
22
–
28
]. Biofilms are difficult to remove and resist many biocides.
Therefore, to prevent the spread of diseases, inhibiting biofilm formation and reducing microbial
attachment are a more promising antimicrobial strategy than killing microbes [17,29].
Many promising antimicrobial polymers have been reported, and the number of FDA-approved
antimicrobial polymers has increased drastically in the past decade [
5
]. This review describes the new
developments in antimicrobial polymers over the past three years. According to the mechanism of
antimicrobial activity, the activity of antimicrobial polymers can be categorized as either passive or
active (Section
2). Based on the polymer material type, antimicrobial polymers can be classified as
bound or leaching antimicrobials (Section 3). These antimicrobial polymers are applied in the medical,
food, and textile industries (Section 4). Finally, the conclusion and prospects for future research are
addressed (Section 5).
2. Passive or Active Action
2.1. Passive Action
A passive polymer layer can reduce protein adsorption on its surface, thereby preventing
the adhesion of bacteria. However, although passive surfaces repel bacteria, they do not actively
interact with or kill bacteria. Due to the mainly hydrophobic and negatively-charged properties
of microbes, passive polymers should be either (1) hydrophilic; (2) negatively-charged; or (3) have
a low surface free energy (Figure 1) [
8
,
30
]. Typical passive polymers comprise (1) self-healing, slippery
liquid-infused porous surface (SLIPS), such as poly(dimethyl siloxane); (2) uncharged polymers, such as
poly(ethylene glycol) (PEG), poly(2-methyl-2-oxazoline), polypeptoid, polypoly(n-vinyl-pyrrolidone),
and poly(dimethyl acrylamide); and (3) charged polyampholytes and zwitterionic polymers, such as
phosphobetaine, sulfobetaine, and phospholipid polymers [
31
,
32
]. Table 2 lists selected passive
polymers and their antimicrobial applications. Among these passive polymers, PEG has been
extensively studied and has demonstrated excellent antimicrobial effects in drastically reducing
protein adsorption and bacterial adhesion. Due to high chain mobility, large exclusion volume,
Int. J. Mol. Sci. 2016, 17, 1578 3 of 14
and steric hindrance effect of highly hydrated layer [
30
], PEG has been the most commonly used
passive antimicrobial material [
33
], and research has shown that it exhibits high antifouling ability to
prevent protein and cell adhesion effectively, consequently preventing the growth of microbes.
Figure 1.
The schematic reaction mechanisms of passive and active action of the antimicrobial polymers.
Table 2. Examples of passive polymers for antimicrobial applications.
Polymer Target Remark Reference
Poly(ethylene glycol)
Staphylococcus aureus,
Escherichia coli,
Pseudomonas aeruginosa
Used as neutral polymer brush systems to
prevent protein and cell adhesion
[
33]
Poly(sulfobetaine methacrylate)
Pseudomonas aeruginosa,
Staphylococcus epidermidis
Resist protein adsorption, cell attachment,
and bacterial adhesion
[
34]
Poly[3-dimethyl
(methacryloyloxyethyl)
ammonium propane
sulfonate-b-2-(diisopropylamino)
ethyl methacrylate]
Staphylococcus aureus
Zwitterionic coronae and pH-responsive cores
can impart bacterial anti-adhesive properties
[
35]
Poly(2-methyl-2-oxazoline) Escherichia coli
Dual-functional antimicrobial surface of
poly(L-lysine)-graft-poly(2-methyl-2-oxazoline)-
quarternery ammonium
[36]
Albumin, whey
Bacillus subtilis,
Escherichia coli
No bacterial growth was observed on
albumin-glycerol and whey-glycerol after
24 h inoculation
[
37]
Polyphenols
Streptococcus mitis,
Fusobacterium nucleatu,
Porphyromonas gingivalis
Effective against periodontal bacteria [38]
2.2. Active Action
Active polymers actively kill bacteria that adhere to the polymer surface. Polymers functionalized
with active agents, such as cationic biocides, antimicrobial peptides, or antibiotics, can kill bacteria on
contact. The mechanism of polymers killing microbes depends on the active agents (Figure 1). The most
widely used active antimicrobial polymers are functionalized with positively-charged quaternary
ammonium, which interacts with the cell wall and destroys the cytoplasmic membrane, resulting in
the leakage of intracellular components and consequent cell death [
20
]. In addition, polyethylenimine,
polyguanidine, and N-halamine are representative polymers that demonstrate active antimicrobial
activity. Polyethylenimine brings about bacterial cell membrane rupture by the electrostatic interaction
between polyethylenimine and the cell membrane. Polyguanidine has bacterial growth inhibition
through adhesion and subsequent disruption of Ca
2+
salt bridges or cell death. N-halamine makes cell
inhibition or inactivation by action of the oxidative halogen targeted at thio or amino groups of cell
receptors [
6
]. Table 3 lists active polymers and their antimicrobial applications, indicating that most of
these new antimicrobials materials are based on quaternary ammonium salts.
Int. J. Mol. Sci. 2016, 17, 1578 4 of 14
Table 3. Examples of active polymers for antimicrobial applications.
Polymer Target Antimicrobial Substance Remark Reference
Nisin-immobilized organosilicon Bacillus subtilis Nisin
Superior antimicrobial activity, and resistant to
several cleaning conditions
[
39]
Polyurethane containing
quaternary ammonium
Staphylococcus aureus, Escherichia coli Quaternary ammonium
Good antimicrobial activities against even at low
concentrations (5 wt %)
[
40]
Poly(n,n-diethylethylendiamine-co-
yrosol-based acrylic)
Staphylococcus epidermidis,
Staphylococcus aureus
Tertiary amine
Combination of two active compounds provide a
synergistic action against biofilms and suppress
reactive species oxygen
[41]
Organosilicon quaternary
ammonium chloride
Staphylococcus aureus Quaternary ammonium
Exerted long-lasting antimicrobial activity for at
least four hours
[
42]
Poly(2-(dimethylamino)ethyl
methacrylate) tethering
quaternary ammonium
Bacillus subtilis, Escherichia coli Quaternary ammonium
Higher C–N
+
content and relatively smooth
morphology would find potential
antimicrobial activity
[
43]
Acrylamide polymers with
quaternary ammonium
Staphylococcus albus, Escherichia coli,
Rhizoctonia solani, Fusarium oxysporum
Quaternary ammonium
Benzyl group attached to nitrogen atom showed
better inhibitory effect on bacteria and
phytopathogenic fungi
[44]
Int. J. Mol. Sci. 2016, 17, 1578 5 of 14
3. Bound or Leaching Antimicrobials
Several recent comprehensive state-of-the-art reviews summarize the progress of and research
on antimicrobial polymers [
6
,
11
]. Antimicrobial polymers can be divided into three types: polymeric
biocides, biocidal polymers, and biocide-releasing polymers [
5
]. Recently, synergistic combination has
been commonly used to provide multiple functional antimicrobials for fighting pathogens.
3.1. Polymeric Biocides
Polymeric biocides are polymers that covalently link bioactive repeating units with antimicrobial
activity such as amino, carboxyl, or hydroxyl groups [
8
,
14
,
18
]. The polymerization process may either
enhance or reduce the antimicrobial activity of bioactive functional groups. Table 4 lists examples of
polymeric biocides synthesized from antimicrobial monomers.
Table 4. Examples of polymeric biocides for antimicrobial applications.
Monomer Target
Antimicrobial
Substance
Remark Reference
μ
Staphylococcus aureus,
Escherichia coli
Sulfonium salt
A high antibacterial activity against
Gram-positive bacteria than
Gram-negative bacteria
[
5]
μ
Staphylococcus aureus,
Escherichia coli
Quaternary
ammonium
Activity depends on the length of
hydrophobic segments
[
20]
μ
Escherichia coli
Quaternary
Ammonium
Antimicrobial dental materials [
20]
μ
Micrococcus luteus,
Staphylococcus aureus,
Bacillus subtilis
Benzimidazole
Against Gram-positive bacterial
strains MIC values 5.4–53.9 µM
[
45]
μ
Staphylococcus aureus,
Escherichia coli
Halogen
Inactivate 100% Staphylococcus aureus
and Escherichia coli with a contact time
of 10 and 30 min
[
46]
μ
Staphylococcus aureus,
Escherichia coli
N-halamine
Excellent biocidal efficacy by
inactivating 100% of the bacteria with
the contact times less than 10 min
[
47]
3.2. Biocidal Polymers
Requiring no bioactive repeating units, the antimicrobial site of biocidal polymers is embodied
by the entire macromolecule. Many biocidal polymers contain cationic biocides, such as quaternary
ammonium, phosphonium, tertiary sulfonium, and guanidinium. Microbes generally have a negative
charge at the outer membrane of the cell. Cationic polymers can lead to the destabilization of the
cell surface and the ultimately induction of bacterial death [19]. The antimicrobial activity of cationic
polymers relate to the charge density of cationic groups.