Cationic Antimicrobial Polymers

Kiran Meghwal, Nirmala Kumari Jangid, Manish Kumar Rawal, Narendra Pal Singh Chauhan and Ritu Tomar 

Cationic polymers mediate transfection via the condensation of nucleic acids, provide protection from enzymatic degradation, and facilitate cellular uptake and endolysosomal escape, making them an excellent candidate for gene delivery. However, their development has also expanded to other applications including drug conjugation and delivery, tissue engineering and therapeutic applications. 

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Antibiotic-resistant bacteria cause life-threatening infections in hospitals and society in general. There is a vital requirement to develop new antimicrobial agents, but this task involves extensive scientific trials. This chapter reviewed broad-spectrum polymeric antimicrobials, which are not susceptible to current resistance, and mechanisms of bacteria to mimic the antimicrobial action of natural HDP, which exert their effect by permeabilising the bacterial cytoplasmic membrane. Most cationic antimicrobial polymers appear to work in a manner similar to membrane-active AMP, such as magainin. The design and synthesis of different polymers, such as methacrylate-based copolymers, PPE, polynorbornene by-products, amphiphilc arylamide polymers and large polymers, have been studied as biomimetic polymers in different applications. 

The use of polymeric ammonium salts and a sulfonic acid salt of sodium is an easy and efficient way of coating fabrics furthermore, employing the layer-by-layer (LbL) deposition technique can broaden the application of N-halamine biocides in other polar substances for use as antimicrobial coatings. Branched PEI, polypropylene (PP) and styrene maleic anhydride copolymers are a very good coating for food packaging materials, possibly due to the presence of both cationic- and N-halamine-forming structures. N-halamine cationic antimicrobial polymers based on (acrylamidopropyl)trimethylammonium chloride, PDDA chloride and poly(2-acrylamido-2-methylpropane sulfonic acid sodium salt) have been synthesised and coated onto cotton fabrics via an LbL deposition technique. 

Poly[2-(dimethylaminoethyl)methacrylate] (pDMAEMA) (Figure 1.1) is a mncoadhesive antimicrobial polymer that is cationic when dissolved in acidified media or if qnaternised with alkylating agents [20, 21]. It can be prodnced cheaply... 

Figure 3.2 Snapshots (a) to (f) of the partitioning of antimicrobial polymers E4 [(m = 4) polymer, with aminobutylene cationic side chains] aggregating into the bilayer. Water and ions are not shown for clarity. The cationic and hydrophobic groups of E4 polymers are shown in blue and red, respectively. Reproduced with permission from U. Baul, K. Kuroda and S. Vemparala, Journal of Chemical Physics, 2014, 141, 084902. 2014, AIP Publishing EEC [23]...

Al-Badri and co-workers [55] studied the effect of fine-tuning the cationic parameter of synthetic mimics of antimicrobial peptides (SMAMP) on haemolytic and antibacterial activities. A category of novel norbornene monomers that carry one, two or three Boc-protected amine-functionalities was synthesised (Figure 3.8). ROMP of the monomers, followed by deprotection of the amine groups led to cationic antimicrobial polynorbornenes that carry one, two and three charges per monomer repeat unit. It was observed that enhancing the number of amine groups on the most hydrophobic polymer effectively decreased its haemolytic activity. 

Functionalised antimicrobial polymers can be developed by chain transfer (reversible addition-fragmentation transfer) polymerisation involving amino derivatives of methacrylate containing polydimethylsiloxane, which are further quarternised to yield new cationic polymers and are useful as antimicrobial coatings. 

All hemolysis results that are reported in this work were obtained using freshly drawn blood from one individual. During the course of this study, the hemolytic activities of polymers were observed to be dependent on the freshness of the blood. Differences were also noted for blood obtained from different individuals. It was determined that blood stored for more than 7 d was more susceptible to hemolysis than freshly drawn blood. These observations were in accordance with previous literature that reported higher susceptibility to hemolysis, caused by a series of cationic antimicrobial peptides, in the case of blood stored for 21 d in 4 C, as opposed to fresh blood (72). Non-hemolytic polymers, dep-poly6, and dep-polylO remained non-hemolytic against old blood that was stored for 3 weeks at 4 °C, and blood from different individuals, with HC50 values above 4000 pg/mL. 

Among intrinsically antimicrobial polymers, cationic polymers have been extensively studied. Their activity is related to their ability to bind to the negatively charged bacterial cell surface promoting cell wall and/or membrane disraption.2 2.2i3... 

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