## 2 Co-Administration of Two Different Antimicrobial Polymers
### Nitric Oxide co-Administration Systems
The commonly accepted mechanism of action of these NPs is the production of ROS, although, in the case of ZnO NPs, the release of Zn\({}^{2+}\) also contributes to its activity. Some interesting studies focused on taking advantage of antimicrobial properties of polymers, as well as NPs, applied on surfaces, coatings or fibers have been reported in the last decade. In the pioneering studies, [PERSON] and coworkers published the enhanced and long-lasting antimicrobial properties of a dual system [94]. In this report, spherical silver bromide nanoparticles (AgBr) were embedded into an antimicrobial polymer matrix of poly(4-vinyl-\(N\)-hexylpyridinium bromide) (NPVP), i.e., a polymer that causes cell death by disrupting the membrane bacteria [95]. The pyridine groups acted as a capping agent stabilizing the AgBr nanoparticles and preventing the formation of agglomerates (see Figure 6). These AgBr nanoparticles are responsible for releasing Ag+ ions. Figure 6: Schematic representation of the preparation of an antibacterial composite material, AgBr/NPVP (NPVP) poly(4-vinylpyridine)-co-poly(4-vinyl-\(N\)-hexylpyridinium bromide). Reproduced with permission from reference [94]. Copyright 2006 ACS. This takes advantage to cause bacteria annihilation by a combination of mechanisms which include inactivating enzymatic functions due to interactions with thiol groups, [96; 97] binding to DNA and disrupting membrane permeability [98]. The effectiveness of the AgBr/NPVP nanocomposite was proven in terms of the low MIC values found against _E. coli_ and _B. Cereus_ (see Table 2). In this additive effect, two mechanisms of action play an important role: On one hand, the amphiphilic polymer damaging the structure of bacteria by contact and, on the other hand, stable AgBr nanoparticles releasing Ag\({}^{+}\) biocidal ions allowing the faster elimination of microbial colonies in comparison to the separated effects of the polymer and AgBr nanoparticles alone. Multiple systems containing different synthetic cationic polymers and metal NPs disclosed in the last decade are summarized in Table 2. The enlisted studies described briefly the mechanism of action to enhance antimicrobial activity. In most cases, positive charges attached to polymers help to bind their chains to the surface of bacteria causing structural damages and increasing permeability allowing the NPs to diffuse quickly into bacteria. In this in-collusion acting process, two mechanisms of action are involved, i.e., contact and release. Adsorption of cationic polymers as well as NPs onto cell may increase the permeability of bacteria facilitating the diffusion of NPs into the interior, prompting the release of ions, disrupting the cell wall, and triggering the ejection of vital components. Furthermore, radicals or oxidative species also attack fundamental components, like DNA and proteins. Likewise, if bacteria exhibit resistance to one of the agents, another one kills the microorganism acting in a different mode. Binary systems are not only limited to coatings. They can be extrapolated to other systems, such as nanofibers. Likewise, other cationic polymers, not containing QAS moieties, have been also proven as efficient antimicrobial agents. In this regard, [PERSON] and coworkers obtained in one-step AgNPs embedded into poly[2-(_tert_-butylaminoethyl) methacrylate] nanofibers (Ag/PTBAM) [99]. The large pendant secondary amino group contained in PTBAM causes phase separation of the lipid layers inside the bacteria resulting in cell death, and it also possesses low toxicity against human cells [100]. Figure 7 details the synthesis of Ag/PTBAM nanofibers by radical-mediated dispersion polymerization. Silver ions (Ag\({}^{+}\)) were first coordinated with hydroxyl groups of poly(vinyl alcohol) (PVA). Subsequently, the TBAM monomer was polymerized. The antibacterial test revealed that a combination of AgNPs and PTBAM enhanced the antibacterial efficacy against _E. coli_\(y\)\(S\).