Chapter 1
Cationic Polymers and Their Applications

Guang Yang, Shun Duan, Fu-Jian Xu

State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, China

1.1 Introduction

Cationic polymers have emerged as a versatile and potent class of antimicrobial agents, particularly in response to the escalating global threat of antimicrobial-resistant bacteria [1]. These macromolecules, characterized by their positively charged functional groups in their main chains and/or side chains, target the negatively charged bacterial cell membranes, causing disruption of cellular integrity and subsequent cell death [2]. Unlike traditional antibiotics that act by targeting specific biochemical pathways, cationic polymers exert their antimicrobial effects through direct physical interactions with bacterial cell membranes. This unique nonspecific mode of action significantly reduces the likelihood of resistance development, positioning cationic polymers as a promising alternative in developing the next-generation of antimicrobial materials [3].

The diversity of cationic polymers in their polymeric structure and composition, encompassing linear, branched, hyper-branched, dendrimer-like, and hybrid systems, has facilitated their adaptability for a wide range of applications [3]. These cationic materials have also demonstrated their remarkable efficacy in preventing and controlling microbial contamination, crossing different fields such as medical device coatings [4], wound dressings [5], environmental water treatment [6], and food packaging [7]. Moreover, customizable chemical structures and functional groups in cationic materials enable precise optimization of their antimicrobial activity, biocompatibility, and environmental sustainability [8, 9], making them invaluable in addressing current challenges in healthcare, industry, and environmental fields [10].

This chapter provides a comprehensive overview of cationic polymers as antimicrobial materials by utilizing insights from some representative research in this field. It begins by defining and classifying cationic polymers, highlighting their structural diversity and functional mechanisms (see Figure 1.1). The subsequent sections categorize the applications of the most studied cationic polymers in various fields according to the referenced previous studies. Each section delves into the specific contributions of cationic polymers from individual studies, concluding with a summary of the advantages, limitations, and future directions for each type of polymer. The chapter concludes with a broad perspective on the challenges and opportunities in this field, emphasizing the potential of cationic polymers to reshape global antimicrobial strategies.

Figure 1.1 Overview of the categorization of cationic polymers and current applications in modern medicine, industry, and agriculture. Of note, R and R3 can be adjusted according to the application scenario of the cationic polymers, which can be hydrophobic alkyl, hydrophilic polyethylene glycol, or other functional groups. In general, R1 can be the quaternary ammonium salts, guanidine, imidazole, and other cationic groups. While R2 can be halides, inorganic fluorides, perfluorinated sulfonamides, or other ionic groups.

Source: Alexander/Adobe Stock Photos

1.2 Classification and Features of Cationic Polymers

Cationic polymers are of great significance for the development of novel antimicrobial agents, both to combat the growing trend of antimicrobial-resistant microorganisms, and to find materials useful for the prevention or treatment of bacterial infections with more specific characteristics in different scenarios. In this section, due to the diversity of cationic polymers, an overview of the most common types of cationic polymers with antibacterial activity is presented, and some representative and recent examples from individual groups are also discussed to further clarify their action mechanisms and practical applications.

1.2.1 Quaternary Ammonium-based Polymers

Quaternary ammonium-based polymers, as applied materials in the field of antimicrobial polymers, are among the most extensively studied in the research community due to their broad-spectrum antimicrobial activity. These type of polymers are permanently positively charged independent of pH value due to their cationic quaternary ammonium moieties and thus can strongly interact with the negatively charged bacterial membranes [11]. This interaction is able to cause irreversible damage to the membrane structure of bacterial cells and subsequent cell death [12]. To our best knowledge, hitherto bacterial resistance to these polymers has not been reported and is generally considered highly unlikely to develop [13]. Hence, quaternary ammonium-based polymers have been utilized across a range of applications, including medical devices, water treatment, food packaging, and textiles.

1.2.1.1 Chemical Structure and Mechanism of Action

Quaternary ammonium-based polymers are relatively simple to prepare, either through the alkylation of polymers containing amine groups or through the polymerization of monomers with ammonium [14]. Although these polymers may differ in terms of polymerization degree or their monomer structure, some studies have focused on researching and summarizing the relationship between their chemical structure and antibacterial performance. First, the strongly positive charges allow cationic polymers themselves to bind onto the negatively charged bacterial cell membrane through electrostatic interaction, during which the density of the positive charge plays a critical role in determining the strength and efficiency of this binding (see Figure 1.2) [15]. Then, as another important parameter, the hydrophobic alkyl chains that are supported by ammonium nitrogen insert into the phospholipid bilayer via hydrophobic and electrostatic interaction. That disrupts the ordered arrangement of phospholipids and increases membrane instability and fluidity, leading to pore formation or even complete membrane disintegration, subsequent leakage of cellular components, and eventually bacterial cell death (see also Figure 1.2) [16]. Guided by this mechanism, various cationic polymers have been developed for efficiently preventing or controlling planktonic bacteria- and biofilm-related infections in different fields [17, 18].

Figure 1.2 Destruction of the cell membrane by quaternary ammonium-based polymers in Gram-positive (Gr+) and Gram-negative (Gr-) bacteria. In detail, quaternary ammonium-based polymers disrupt bacterial cell membranes in a three-step process. First, the cationic polymers are electrostatically attracted to the negatively charged bacterial membrane. Then, the hydrophobic segments of the polymers insert and penetrate the lipid bilayer. Finally, these hydrophobic chains destabilize the bilayer through combined electrostatic and hydrophobic interactions, compromising the integrity of the bacterial membrane, cellular contents leakage, and ultimately bacterial cell death.

1.2.1.2 Applications of Quaternary Ammonium-based Polymers

1.2.1.2.1 Medical Devices and Healthcare

Quaternary ammonium-based polymers have been widely used in medical device coatings to prevent biofilm formation and device-associated infections. Implantable devices, such as catheters and orthopedic implants, are highly susceptible to microbial adhesion, colonization, and subsequent biofilm formation after being implanted in the human body, leading to serious, life-threatening bacterial infections and complications. Quaternary ammonium-based polymers can be coated onto the surface of these implantable devices to provide durable antimicrobial activity. For example, the benzyl quaternary ammonium salt containing polycarbonates was coated onto the pristine silicone substrate of the urinary catheter, yielding 5 log-units and 3 log-units killing planktonic Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli), respectively. Moreover, the antibacterial and antifouling activities of this coating remained unchanged after being incubated with S. aureus suspension over 14 days [19]. In addition to this, advanced hydrogels incorporating quaternary ammonium groups were also developed as the antibacterial coating of orthopedic implants, which not only led to a higher than 1 log-unit reduction of two Gram-positive bacterial strains in vitro but also almost fully eradicated the infection from the femoral fracture of intramedullary nail fixation in rats within 42 days [20].

1.2.1.2.2 Water Treatment

In the field of environmental applications, quaternary ammonium-functionalized membranes are highly effective in removing microbial contaminants from drinking water and industrial effluents. Studies have shown epoxy propyl dimethyl dodecyl ammonium chloride-grafted cellulose acetate (CA) membrane (QCA-X) presented an improved filtration capacity and antifouling performance compared with CA membranes in the process of water treatment. Meanwhile, this QCA-X membrane showed excellent antibacterial performance, and the sterilization efficacy against S. aureus...