Nanomaterials for Antibiofilm Activity - ACS Publications

Chapter 6

Nanomaterials for Antibiofilm Activity

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Surya Prakash Singh and Aravind Kumar Rengan* Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy, Hyderabad 502285, India *E-mail: [email protected].

The community established by the association of microorganisms such as bacteria, yeast, or fungi leads to biofilm formation. Microorganisms are embedded in the extracellular polymeric matrix of biofilm adhering to biotic and abiotic surfaces or substratum. Biofilm can grow on medical devices, living tissues, or implants and cause infection in patients. Biofilm is a resistant microbial community due to the expression of the gene that causes its resistance to antibacterial agents and human immunity. These microbial infections are prone to occur in healthcare facilities and are the major sources of morbidity and mortality among patients. Cardiac implants based on cardiac implantable electronic devices–related infections account for 30% of death due to infection associated with Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia, Escherichia coli, Acinetobacter baumannii, Staphylococcus epidermidis, and Propionibacterium acnes. This chapter includes the role of nanoparticles in the prevention of biofilm on medical devices and human implants. Nanoparticles have important physicochemical properties that inhibit the proliferation of infectious microorganisms and prevent biofilm formation. Nanoparticles follow diverse mechanisms for antibiofilm activities leading to oxidative damage and genetic changes in microorganisms. Nanoparticles could be superior alternatives to conventional antibiotics. Various types of nanomaterials based on lipids, polymers, and metals show excellent potential toward antimicrobial growth. Nanomaterial coverings or coatings on medical devices, healthcare kits, and implants can overcome the biofilm associated with infection and mortality.

© 2019 American Chemical Society

Rathinam and Sani; Introduction to Biofilm Engineering ACS Symposium Series; American Chemical Society: Washington, DC, 2019.

Nanotechnology Strategy for Antibiofilm Activity Biofilms are the association of organized colonies formed from fungi, bacteria, or yeast. These organisms adhere to each other on biotic or abiotic surfaces within self-produced extracellular polymeric substances. This phenomenon leads to expression of the resistant gene, and phenotypic changes in microorganisms cause its prevention from nutrient limitation, antibacterial agents, and immunological defense systems (1, 2). In this perspective, the drug and antibiotic interaction for the treatment becomes ineffective. Microorganisms can adhere to synthetic polymers, medical devices, or transplant materials, leading to the development of biofilms (3). The detachment of microorganisms from mature biofilms leads to transmission of infection. According to a report, biofilm development causes 80% of microbial infections (4). These microbial infections are prone to occur in healthcare facilities and lead to 100,000 deaths per year in the United States (4, 5). Nanotechnology strategies have been adopted for many biomedical applications. Nanomaterial development for antibiofilm activity could be a promising approach. Nanoparticles (NPs) loaded with a drug could overcome the drawbacks of conventional antibiotic treatments due to different routes of internalization. NPs can act as potential delivery vehicles for the specific delivery of the drug molecule. NPs can protect the doped drug molecules from the enzymatic degradation and enhance the accumulation at the target site (6). Nanomaterials at nanometer scale exhibit exclusive physicochemical properties because of higher surface area to volume ratio. NPs can easily penetrate microorganisms because the NPs’ size is the same as the order of biological cells. NPs can enter biofilm and interact with the microbial layer, leading to irreversible damage to biological macromolecules (cell membrane and DNA) (7). Various nanotechnology strategies have been adopted for antibiofilm activities, including lipid-based NPs, polymeric NPs, biologically active metallic nanocomposites, and stimuli-responsive smart NPs.

Parameters To Control Biofilm Formation The success of nanoparticle-based treatment against biofilm formation depends on the accessibility of nanomaterials at the infected site. Some parameters are important for selecting appropriate NPs to inhibit the proliferation of infectious microorganisms (3). The surface chemistry of nanoscale particles is a very attractive point. Many studies have been done on eukaryotic cells, whereas fewer studies are reported for bacterial cells. The fabrication of nanoscale topography with nanoroughness can prevent the adherence of microorganisms and consequently biofilm formation (e.g., endotracheal tubes with nanoroughness) (8, 9). In order to enhance the binding efficiency of the NPs to the target site in biofilm, NP size and charge are decisive parameters. Smaller-diameter NPs have a better chance of penetrating biofilm NPs can exhibit superior antimicrobial effect by inhibiting the proliferation of microbial cells. Because the bacterial cell walls have a negative charge, more positively charged NPs could easily interact with the cell surface. Having high-positive zeta potential causes the oppositely charged NPs to undergo membrane disruption and exhibit high antimicrobial effect. (3, 9). Nanomaterials loaded with a drug could reduce the adverse drug toxicity and enhance the stability, improving the sustained release of the drug (10).

Types of Nanomaterials for Antibiofilm Activity To achieve antibiofilm activity, various approaches including photodynamic therapy, electrical therapy, and ultrasound have been used (11). Other methodologies used against biofilm activity such as antiadhesive surface modifications (12), polymer-coated devices (13), antifouling coatings 126 Rathinam and Sani; Introduction to Biofilm Engineering ACS Symposium Series; American Chemical Society: Washington, DC, 2019.

(14), use of antimicrobials over the surface of medical devices (15, 16), immobilization or coating of biomolecules (17, 18), and nanomaterial-based strategy showed potential against biofilm activity. The way nanomaterial internalization and mechanism of antibacterial effect works is different from traditional antimicrobials, contributing to an attractive alternative (10). Lipid-Based Nanoparticles The microbial cell membrane is impermeable to hydrophobic drug molecules. Development of a nano carrier for such molecules can improve the solubility of hydrophobic drug molecules. Lipidbased NPs can be helpful for entrapment of such aqueous drugs. Liposomes that are biodegradable and biocompatible can be used to deliver antifungals, vaccines, and antimicrobial and imaging agents. Liposome is a bilayer structure made up of lipid as the main constituent,and it has hydrophobic space inside for entrapment of hydrophobic drug molecules. Liposome-entrapping antimicrobial agents showed inhibition of biofilm formation by delivery of antimicrobial agents at biofilm interfaces. A positive reaction with visible fusion was observed between rhodamine-labeled liposomes and intracellular pathogens (Pseudomonas aeruginosa). Rhodamine-labeled liposomes phagocytosed by intracellular pathogens, show red emission (Figure 1) (19–22).

Figure 1. Liposome–bacterium interactions, P. aeruginosa (fluorescent microscopic image). (a) Free rhodamine B, penetration into the bacterial cells. (b) Transparent microscopy image. (c) Rhodamineliposomes and bacterial cell interaction (red light emission of bacterial cell membranes). (d) Transparent microscopy image. Reproduced with permission from reference (20). Copyright 2009 Elsevier.

127 Rathinam and Sani; Introduction to Biofilm Engineering ACS Symposium Series; American Chemical Society: Washington, DC, 2019.

Liposomes have both hydrophilic and hydrophobic pockets for carrying aqueous and nonaqueous soluble agents, respectively. They also enhance the retention time of drugs by slowing down the clearance rate (23). Liposomes loaded with drugs prevent the formation of protease, lipase, and chitinase as well as the production of biofilm of Acinetobacter baumannii, Escherichia coli, Bordetella bronchiseptica, Acinetobacter lwoffii, P. aeruginosa, and Klebsiella pneumonia (24). Liposomal nanoformulations are also useful for antibiofilm activity on the interfaces of medical instruments and devices. Coating of ciprofloxacin-loaded liposomes sequestered with polyethylene glycol onto the surface of catheters prevents the adherence of bacterial colonies (25). To prevent nosocomial urinary tract infection over the catheters, ciprofloxacin-loaded liposomal hydrogels were integrated on silicon Foley catheters. This catheter prevents the infection of virulent E. coli at the urethral meatus, and 30% reduction was observed in the rate of bacteriuria (26). Another lipid-based material for biofilm prevention is based on solid lipid nanoparticles (SLN). Eugenol-loaded SLN as an antimicrobial agent showed antifungal activity in a rat model with oral candidiasis (27). SLN formulation of tilmicosin loaded with PVA-hydrogenated castor oil has shown antibiofilm activity in Staphylococcus aureus-induced mastitis in a murine model (28). Polymeric Nanoparticles In addition to antibiofilm activity, polymer-based nanocarriers have gained much importance in the medical field. Polymeric carriers are biocompatible and biodegradable. Polymer-based NPs used as drug carriers include hydrogel-type materials, micelles, and microspheres of the polymer. Poly [dl-lactic acid] and poly [ε-caprolactone] are biodegradable polymers used as a reservoir for rifampicin and ofloxacin. This coating used an airbrush spray system and layer-by-layer coating around the mesh-like filament for dual drug release (29). These meshes had improved antibiofilm properties with excellent inhibition of bacterial growth and adhesion. Another example of coated mesh with poly [ε-caprolactone]– containing ofloxacin showed controlled and prolonged release of the drug against S. aureus, E. coli, Staphylococcus epidermidis, and some Gram-positive cocci (30, 31). Prolonged bacterial infection leads to the formation of biofilm and inflicts a heavy burden on patients due to local immune defense and resistance to conventional antimicrobial drugs. Protein-based polymeric NPs are an alternative for antibiofilm activity. In this addition, hybrid material based on polyethylene glycol (PEG) and cationic human serum albumin (cHSA) overcame conventional drug resistance and exhibited antimicrobial activity. The polymeric hybrid material, PEG (2000)18-cHSA (optimal ratio) showed a potent armament against drug resistance and biofilm-related infection. PEG (2000)18-cHSA showed reduced hemolytic activity and an enhanced binding affinity of the hybrid NPs to bacteria cell wall components. These NPs were less susceptible to drug resistance and exhibited potent action against drug-resistant bacteria strains. The NPs killed bacteria by membranolytic mechanism and finally disrupted the biofilm (32). Nanocomposite based on goldcoated chitosan polymers acted as a potential biofilm-disrupting agent. Gold nanocomposite generated by reduction of chloroauric acid in the presence of chitosan polymers with small molecule 2-mercapto-1-methylimidazole (MMT) finally produced a functional gold nanocomposite (CSAu@MMT). The functional gold NP with the cationic amine on its surface permitted enhanced uptake of CS-Au@MMT to the negatively charged bacterial cell surface via electrostatic adhesion. The gold nanocomposites with MMT exerted enhanced antibacterial effect and slowed down the biofilm formation as shown in Figure 2. CS-Au@MMT also was effective against the infection induced by mature biofilms due to their higher penetration and sustained damage to bacterial cells, making it a useful material for biomedical and industrial applications (33). 128 Rathinam and Sani; Introduction to Biofilm Engineering ACS Symposium Series; American Chemical Society: Washington, DC, 2019.

Figure 2. (a) Schematic diagram of the synthesis of CS-Au@MMT NPs and their use in disruption of mature biofilm. Fluorescence micrographs of (b) E. coli and (c) S. aureus stained with PI (red fluorescence: dead bacteria) and SYTO9 (green fluorescence: live bacteria) after treatment with CS, CS-Au, and CSAu@MMT. (d) Minimal inhibitory concentration (MIC) of different nanocomposites against E. coli (left columns) and S. aureus (right columns). (e) Antibacterial activity of nanocomposites against E. coli and S. aureus. (f) SEM images of E. coli and S. aureus after treatment with CS-Au@MMT. Reproduced with permission from reference (33). Copyright 2018 Elsevier. Metal-Based Nanoparticles Inorganic and metallic-based nanomaterials have unique physiochemical properties useful for medical applications. NPs based on metals such as silver, gold, magnesium, copper, and iron can be used as antimicrobial agents. Nanomaterials have significant potential for antimicrobial effect. In the past few years, silver-based NPs have been explored and investigated for their biological importance in the medical field. Silver-based NPs have interesting physiochemical characteristics 129 Rathinam and Sani; Introduction to Biofilm Engineering ACS Symposium Series; American Chemical Society: Washington, DC, 2019.

such as inherent antibacterial, anti-inflammatory, antifungal, and antiviral activities that are suitable for various biotechnological applications (34). They are also known for their toxic effects. To avoid the toxicity of AgNPs, they can be stabilized with thermoreversible and biocompatible hydrogel Pluronic F-127. This gel formulation with the combination of Pluronic F-127 and AgNPs could be useful for the prophylactic treatment of microbial-affected wounded skin. According to studies, the formulations of gel with 250 ppm of AgNPs showed total inhibition of in vitro biofilm activity formed by clinical strains (P. aeruginosa and S. aureus) (35). Another way to the synthesis of safe and low-cost AgNPs is green synthesis. According to studies based on agriculture waste, coconut, scientifically named Cocosnucifera, shell has been used for green synthesis of AgNPs. Coconut-shell extract mediated synthesis of AgNPs (CSE-AgNPs) and exhibited antibiofilm activity against human pathogens such as Listeria monocytogenes, Salmonella typhimurium, S. aureus, and E. coli (36). The low concentrations of AgNPs (250 ppm) to the primer Scotchbond Multi-Purpose Adhesive System showed negligible cytotoxicity of AgNPs. The final concentration of 250 ppm AgNPs along with primer showed biocompatibility. The resultant AgNPs primer complex exhibited both antibiofilm activities and reliable bond strength for the tooth-adhesive interface. The complex could be applicable for increasing dental restoration longevity and perfection of conventional dental adhesives efficacy (37). The bimetallic nanoparticle-based on gold and silver showed enhanced antimicrobial properties that further improve the therapeutic efficacy for antibiofilm activity. The bimetallic NP was synthesized bacteriogenically by using Shewanella oneidensis MR-1 (γproteobacterium). Gold–silver NPs were found to be more effective than other NPs. The minimum inhibitory concentration (MIC) for tested microbes was found to be 30–50 µM, whereas other NPs’ MICs were >100 µM. Gold–silver NPs were small, and the combination further enhanced the bacterial cell internalization, ultimately leading to bacterial inactivation. The bimetallic NP was effective against bacterial biofilm formed from Gram-positive bacteria (S. aureus and Enterococcus faecalis) and Gram-negative bacteria (P. aeruginosa and E. coli (38). Patients with burn wounds and cystic fibrosis have a higher chance of infection with P. aeruginosa, which further leads to biofilm formation. The gold nanoparticles (AuNPs) also exhibit antibiofilm activity. A novel one-step biosynthesis of AuNPs was reported by using a phytochemical, hordenine (HD), which acts as a reducing as well as a capping agent. The resultant NPs, HD-AuNPs, showed significant antibiofilm activity against P. aeruginosa (39). Au/Ag core-shell NPs having a gold core and a silver shell were conjugated with subtilisin (AuAgSNP) to improve its biocompatibility. Subtilisin prevents biofilm formation by degrading the bacterial surface proteins and enhancing the fibroblast proliferation. AuAgSNP immobilized on polycaprolactam exhibited antibacterial and antibiofilm behavior against E. coli and S. aureus (40). Chemical and green methods were used to develop silver/chitosan nanocomposites for antibiofilm coating on medical devices. This process used sodium borohydride and linden extract. AgNPs immobilized on chitosan biopolymer improved its biocompatibility and prevented the NPs agglomeration.The resultant NPs showed enhanced antimicrobial properties and could be used as effectual antibacterial coating to avoid biofilm formation (41).

Mechanisms of Nanoparticles for Biofilm Control The mechanism of antibiofilm activities of nanocomposite materials may differ in the generation of free-radical formation, and oxidative stress leads to genetic damage. NPs based on metal oxides such as TiO2 cause lipid peroxidation by cytotoxic reactive oxygen species (ROS) production in microbial cells. Respiratory activity gets reduced due to the oxidation of enzymes, which further leads to microbial cell death (42). The physicochemical properties of NPs, which includes shape, size, 130 Rathinam and Sani; Introduction to Biofilm Engineering ACS Symposium Series; American Chemical Society: Washington, DC, 2019.

and surface charge, have a very important role in antimicrobial activity (43, 44). The DNA damage, DNA unwinding, and cell membrane disruption by NPs are also responsible for antimicrobial activity (45, 46). The interaction between NPs and protein thiols can disrupt the metabolic pathways and leads to antibiofilm activity (47). It is reported that AgNPs inhibit the biofilm formation by P. aeruginosa and S. epidermidis up to 95% even 24 h after treatment (48). The probable mechanism reported for disruption of biofilm matrices by AgNPs could be due to distressing intermolecular forces. The interaction of silver ions with sulfhydryl moieties present on bacterial cell walls leads to disruption of the cell membrane and restricts the cellular proliferation. The antibacterial activity of AgNPs is due to silver ions having a strong tendency to interact with the phosphate group of DNA and the thiol group present in the enzyme. Silver ions can intercalate between the bases of DNA (purine and pyrimidine) that further perturb the hydrogen bonding between the two antiparallel strands, leading to DNA denaturation. AgNPs could impinge on the phosphotyrosine profile of bacterial peptide, thus influencing cell signaling pathways and inhibiting bacterial growth. AgNPs could inhibit protein synthesis by interfering with 30S ribosomal subunits. AgNPs could generate ROS, leading to oxidative stress–mediated cell death as shown in Figure 3 (49).

Figure 3. Schematic illustration of plausible molecular mechanisms of AgNPs in opposition to bacterial cells. Reproduced with permission from reference (49). Copyright 2015 Elsevier. AuNPs alone have little or no antimicrobial activity (50). Because AuNPs are inert in nature and nontoxic to cells, they can be conjugated with antibiotics (51) or active biomolecules to attain definite antibiofilm activities (52). Bacteria, yeasts, or fungi form heterogeneous entities by secreting 131 Rathinam and Sani; Introduction to Biofilm Engineering ACS Symposium Series; American Chemical Society: Washington, DC, 2019.

extracellular polymeric substances (EPS) on abiotic or biotic surfaces that further leads to the formation of biofilms. The functionalized polystyrene NPs interact with SO4– groups of EPS by hydrophobic complexation, causing disruption of bacterial biofilm (53). Polymeric NPs with a polycationic group cause disruption of cellular membranes by ion exchange interaction between the charged polymer and the bacterial cell surface. Stimuli-responsive smart NPs are also an alternative for controlling biofilm formation in that they prevent infections on medical implants or devices by means of their particular mechanisms of actions. Polymeric NPs loaded with antimicrobial agents, antibiotics, or bacteriostatic peptides can interfere with microbial growth and prevent biofilm formation (54). Magnetic nanoparticles (MNPs) can absorb electromagnetic radiation, leading to hyperthermia production. The heat generated via MNPs is used to kill bacterial biofilms (55). NPs conjugated with photosensitizers are one of the alternatives for killing microbial pathogens associated with biofilm formation on medical devices. Photodynamic therapy (PDT) is widely used for destroying pathogens. PDT includes photosensitizers, the specific wavelength of light, and molecular oxygen; the combination of these three can generate cytotoxic ROS, which elicits bacterial cell wall lysis and prevents biofilm formation (56, 57). Methicillin-resistant S. aureus (MRSA) is a bacterium that causes infections in diverse parts of the body and on medical devices. MRSA is tough to treat. NPs functionalized with photosensitizers such as methylene blue or porphyrin significantly inactivated MRSA (58).

Antibiofilm Devices Based on Nanomaterials In the United States, more than 100,000 cardiac implantable electronic devices (CIEDs) are implanted annually. CIEDs, including implantable cardioverter defibrillators, percutaneous pacemakers, and cardiac resynchronization therapy devices, have been used for managing heart failure. Cardiac implant infections account for 30% of death due to infection associated with P. aeruginosa, S. aureus, K. pneumonia, E. coli, A. Baumannii, S. epidermidis, and Propionibacterium acnes (59). The overgrowth of these microorganisms leads to thicker biofilm formation on prosthetic valves, pacemakers, and coronary artery bypass grafts, which set hurdles for the use of these implant devices (60, 61). To overcome the biofilm-associated problems of medical devices, nanoparticlebased approaches are being used (Table 1). The microbial growth in breast tissue and ducts are consequences of biofilm formation around breast implants that leads to capsular contractions (62, 63). It is reported that S. epidermis is liable for biofilm formation on breast implant surfaces (64). The different nanomaterials used to cover the medical devices and implants are listed in Table 1.


Table 1. Nanoparticle-Based Approaches for Antibiofilm Activity Nanomaterial for antibiofilm activity

Antibiofilm device/implant

133

Silicone NPs

Breast implants

Nitric oxide-releasing NPs

Central venous catheters

Polymeric NP-based photodynamic therapy

Orthopedic implants

Zinc oxide nanoparticles (ZnO NP)–incorporatedtitanium implants

Orthopedic implants

Ciprofloxacin-loaded nanochitosan-coated Ti implants Silver nanoparticle–coated surfaces

Orthopedic implants

Silver-conjugated NPs

Prosthetic heart valve

Ag-Ti nanocomposites

Face masks

Silver-impregnated pedicle screw

Description Nanosilicone can reduce the immune responses generated by human peripheral blood mononuclear cells under in vivo condition that can be implicated for breast implants. Nitric oxide-releasing nanoparticles (NO-NPs) can exhibit antibiofilm activity. NO-NPs restrict biofilm formation by interfering with S. aureus growth and adhesion on a rat central venous catheter model of infection. Antimicrobial photodynamic therapy (aPDT) is progressively being revolutionized for treatment of periodontitis. aPDT with methylene blue (MB)–loaded poly(lactic-co-glycolic) nanoparticles in the presence of red light at 660 nm showed protection against human dental plaque bacteria both in suspensions and in biofilms. ZnO NP–incorporated titanium implants can be useful in two different ways.Ti surfaces are helpful in promoting mammalian cell adhesion and, in contrast, inhibiting bacterial adhesion. ZnO NP–incorporated titanium implants include titania nanotube, titania nanoleaf, and presence of ZnO NP as an antibacterial agent on Ti nano surface. Titanium surface coated with ciprofloxacin-loaded chitosan nanoparticles prevents titanium implant–related infections. Silver-impregnated pedicle screw has shown antibiofilm activity and inhibits biofilm formation.

Reference (65)

(66) (67)

(68)

(69) (70)

Pulsed laser deposition technique used to deposit a thin film of AgNPs (71) over the surface of pyrolytic carbon interferes with bacterial growth and colonization. Useful in prosthetic heart valve implants. Ag-Ti nanocomposite–coated facemasks prevent the growth of infectious (72) agents. The minimum inhibitory concentrations of the nanocomposite against S. aureus and E.coli were found to be 1/512 and 1/128, respectively.


Table 1. (Continued). Nanoparticle-Based Approaches for Antibiofilm Activity Nanomaterial for antibiofilm activity

Antibiofilm device/implant

Description

Reference

134

Surface-engineered AuNPs

Ventricular drain catheters

Surface-engineered AuNPs showed biofilm disruption and have bactericidal activity. Effective against ventilator-associated pneumoniapathogens such as S.aureus and P. aeruginosa.

(73)

Nanosilver-endodontic filling and dental adhesives

Dental adhesive, endodontic filling

(74)

Nanostructured titania coating with AgNPs

Endodontic filling, oral implants

Polyethylene glycol (PEG)-stabilized lipid NPs

Endodontic filling, bone cements

Silica NPs

Contact lenses

Zinc-doped copper oxide (Zn-CuO) nanocoating

Contact lenses

The antibacterial activity of modified nanosilver for endodontic filling and dental adhesives was evaluated. Dental cement modified with nanosilver showed protection against Streptococcus mutans (microorganisms typically responsible for initiation of tooth decay). Nanostructured titania coated with AgNPs are fabricated on Ti oral implants and endodontic fillings. Titania nanotubes loaded with AgNPs can kill all the planktonic bacteria and exhibited long-term antibacterial activity with good tissue integration. Terpinen-4-ol is a bioactive component extracted from tea tree oil. This component showed broad spectrum antimicrobial activity. However, the drawback associated with terpinen-4-ol because of its nonwet ability and high volatilization limited its application. The PEG-stabilized lipid nanoparticle encapsulating terpinen-4-ol can be used for endodontic filling and bone cements. Silica nanoparticle-based brush coating to polypropylene cases restricts the bacterial adhesion up to tenfold compared with uncoated polypropylene. Coating of nanoformulation decreases microbial spread from lens cases to contact lenses. Coating of nanoparticles of Zn-CuO nanocoating. The active nanoparticles based on Zn-CuO that were deposited onto the surface of the contact lens showed antibiofilm activity and restricted the microbial growth.


(75)

(10)

(76)

(77)

Summary Microbial survival has become prominent because of biofilm establishment. The phenotypic changes of microorganisms with the expression of resistance genes hinder the action of beta-lactam drugs. The rise of microorganisms resistant to conventional antibiotics and antimicrobial agents causes a need to identify capable alternative therapies. Biofilm formation accounts for about 80% of microbial infections leading to mortality due to transmission of infection. Nanotechnology-based approaches to overcome resistance and biofilm containment are rapidly evolving. Nanomaterials are exceedingly helpful in both avoidance of and eradicating biofilms. Various types of NPs and nanocomposites based on lipid, polymer, and metal with the verified potential of antimicrobial properties have been very effective against biofilm formation. Such nanoparticle-based coatings on medical devices and implants could be useful for preventing biofilm formation and transmission of microbial infections as well. However, some key parameters such as surface charge, particle diameter, and nanoscale topography are crucial for the selection of ideal NPs. Research focus in the current scenario is dynamic in these areas to develop medical devices and implants with antibiofilm activities. These medical devices and implants with nanoparticle-based antibiofilm activities are biocompatible and cost-effective and could set new standards for the impediment of biofilms.

References 1.

Ramasamy, M.; Lee, J. Recent Nanotechnology Approaches for Prevention and Treatment of Biofilm-Associated Infections on Medical Devices. Biomed. Res. Int. 2016, 1851242. 2. Whitchurch, C. B.; Tolker-Nielsen, T.; Ragas, P. C.; Mattick, J. S. Extracellular DNA Required for Bacterial Biofilm Formation. Science 2002, 295, 1487. 3. Vianna Santos, R. C. Antibiofilm Applications of Nanotechnology. Fungal Genomics Biol. 2014, 4, 1–2. 4. Epstein, A. K.; Hochbaum, A. I.; Kim, P.; Aizenberg, J. Control of Bacterial Biofilm Growth on Surfaces by Nanostructural Mechanics and Geometry. Nanotechnology 2011, 22, 494007. 5. Pelgrift, R. Y.; Friedman, A. J. Nanotechnology as a Therapeutic Tool to Combat Microbial Resistance. Adv. Drug Deliver. Rev. 2013, 65, 1803–1815. 6. Taylor, E.; Webster, T. J. Reducing Infections Through Nanotechnology and Nanoparticles. Int. J. Nanomed. 2011, 6, 1463–1473. 7. Suci, P. A.; Berglund, D. L.; Liepold, L.; Brumfield, S.; Pitts, B.; Davison, W.; Oltrogge, L.; Hoyt, K. O.; Codd, S.; Stewart, P. S.; Young, M.; Douglas, T. High-Density Targeting of a Viral Multifunctional Nanoplatform to a Pathogenic, Biofilm-Forming Bacterium. Chem. Biol. 2007, 14, 387–398. 8. Machado, M. C.; Tarquinio, K. M.; Webster, T. J. Decreased Staphylococcus aureus Biofilm Formation on Nanomodified Endotracheal Tubes: A Dynamic Airway Model. Int. J. Nanomed. 2012, 7, 3741–3750. 9. Seil, J. T.; Webster, T. J. Antimicrobial Applications of Nanotechnology: Methods and Literature. Int. J. Nanomed. 2012, 7, 2767–2781. 10. Sun, L. M.; Zhang, C. L.; Li, P. Characterization, Antibiofilm, and Mechanism of Action of Novel PEG-Stabilized Lipid Nanoparticles Loaded with Terpinen-4-Ol. J. Agric. Food Chem. 2012, 60, 6150–6156.


11. Kasimanickam, R. K.; Ranjan, A.; Asokan, G. V.; Kasimanickam, V. R.; Kastelic, J. P. Prevention and Treatment of Biofilms by Hybrid- and Nanotechnologies. Int. J. Nanomed. 2013, 8, 2809–2819. 12. Neoh, K. G.; Kang, E. T. Combating Bacterial Colonization on Metals via Polymer Coatings: Relevance to Marine and Medical Applications. ACS Appl. Mater. Interfaces. 2011, 3, 2808–2819. 13. Li, L.; Molin, S.; Yang, L.; Ndoni, S. Sodium Dodecyl Sulfate (SDS)-Loaded Nanoporous Polymer as Anti-Biofilm Surface Coating Material. Int. J. Mol. Sci. 2013, 14, 3050–3064. 14. Banerjee, I.; Pangule, R. C.; Kane, R. S. Antifouling Coatings: Recent Developments in the Design of Surfaces That Prevent Fouling by Proteins, Bacteria, and Marine Organisms. Adv. Mater. 2011, 23, 690–718. 15. Kwok, C. S.; Horbett, T. A.; Ratner, B. D. Design of Infection-Resistant Antibiotic-Releasing Polymers. II. Controlled Release of Antibiotics Through a Plasma-Deposited Thin Film Barrier. J. Control. Release. 1999, 62, 301–311. 16. Shintani, H. Modification of Medical Device Surface to Attain Anti-Infection. Trends Biomater. Artif. Organs. 2004, 18, 1–8. 17. Khoo, X.; Hamilton, P.; O’Toole, G. A.; Snyder, B. D.; Kenan, D. J.; Grinstaff, M. W. Directed Assembly of PEGylated-Peptide Coatings for Infection-Resistant Titanium Metal. J. Am. Chem. Soc. 2009, 131, 10992–10997. 18. Arciola, C. R.; Campoccia, D.; Speziale, P.; Montanaro, L.; Costerton, J. W. Biofilm Formation in Staphylococcus Implant Infections. A Review of Molecular Mechanisms and Implications for Biofilm-Resistant Materials. Biomaterials 2012, 33, 5967–5982. 19. Alipour, M.; Halwani, M.; Omri, A.; Suntres, Z. E. Antimicrobial Effectiveness of Liposomal Polymyxin B Against Resistant Gram-Negative Bacterial Strains. Int. J. Pharm. 2008, 355, 293–298. 20. Drulis-Kawa, Z.; Dorotkiewicz-Jach, A.; Gubernator, J.; Gula, G.; Bocer, T.; Doroszkiewicz, W. The Interaction Between Pseudomonas aeruginosa Cells and Cationic PC:Chol:DOTAP Liposomal Vesicles versus Outer-Membrane Structure and Envelope Properties of Bacterial Cell. Int. J. Pharm. 2009, 367, 211–219. 21. Nightingale, S. D.; Saletan, S. L.; Swenson, C. E.; Lawrence, A. J.; Watson, D. A.; Pilkiewicz, F. G.; Silverman, E. G.; Cal, S. X. Liposome-Encapsulated Gentamicin Treatment of Mycobacterium Avium- Mycobacterium Intracellulare Complex Bacteremia in AIDS Patients. Antimicrob. Agents Chemother. 1993, 37, 1869–1872. 22. Pinto-Alphandary, H.; Andremont, A.; Couvreur, P. Targeted Delivery of Antibiotics Using Liposomes and Nanoparticles: Research and Applications. Int. J. Antimicrob. Ag. 2000, 13, 155–168. 23. Jones, M. N.; Song, Y. H.; Kaszuba, M.; Reboiras, M. D. The Interaction of Phospholipid Liposomes with Bacteria and Their Use in the Delivery of Bactericides. J. Drug Target. 1997, 5, 25–34. 24. Alhariri, M.; Omri, A. Efficacy of Liposomal Bismuth-Ethanedithiol-Loaded Tobramycin After Intratracheal Administration in Rats with Pulmonary Pseudomonas aeruginosa Infection. Antimicrob. Ag. Chemother. 2013, 57, 569–578. 25. Jesorka, A.; Orwar, O. Liposomes: Technologies and Analytical Applications. Annu. Rev. Anal. Chem. 2008, 1, 801–832. 136 Rathinam and Sani; Introduction to Biofilm Engineering ACS Symposium Series; American Chemical Society: Washington, DC, 2019.

26. Finelli, A.; Burrows, L. L.; DiCosmo, F. A.; DiTizio, V.; Sinnadurai, S.; Oreopoulos, D. G.; Khoury, A. E. Colonization-Resistant Antimicrobial-Coated Peritoneal Dialysis Catheters: Evaluation in a Newly Developed Rat Model of Persistent Pseudomonas aeruginosa Peritonitis. Perit. Dial. Int. 2002, 22, 27–31. 27. Garg, A.; Singh, S. Enhancement in Antifungal Activity of Eugenol in Immunosuppressed Rats Through Lipid Nanocarriers. Colloids Surface B Biointerfaces 2011, 87, 280–288. 28. Wang, X. F.; Zhang, S. L.; Zhu, L. Y.; Xie, S. Y.; Dong, Z.; Wang, Y.; Zhou, W. Z. Enhancement of Antibacterial Activity of Tilmicosin Against Staphylococcus aureus by Solid Lipid Nanoparticles in Vitro and in Vivo. Vet. J. 2012, 191, 115–120. 29. König, D. P.; Schierholz, J. M.; Münnich, U.; Rütt, J. Treatment of Staphylococcal Implant Infection with Rifampicin-Ciprofloxacin in Stable Implants. Arch. Orthop. Trauma Surg. 2001, 121, 297–299. 30. Engelsman, A. F.; van der Mei, H. C.; Ploeg, R. J.; Busscher, H. J. The Phenomenon of Infection with Abdominal Wall Reconstruction. Biomaterials 2007, 28, 2314–2327. 31. Blumberg, H. M.; Rimland, D.; Kiehlbauch, J. A.; Terry, P. M.; Wachsmuth, I. K. Epidemiologic Typing of Staphylococcus aureus by DNA Restriction Fragment Length Polymorphisms of RRNA Genes: Elucidation of the Clonal Nature of a Group of Bacteriophage-Nontypeable, Ciprofloxacin-Resistant, Methicillin-Susceptible S. aureus Isolates. J. Clin. Microbiol. 1992, 30, 362–369. 32. Obuobi, S.; Wang, Y.; Khara, J. S.; Riegger, A.; Kuan, S. L.; Ee, P. L. R. Antimicrobial and Anti-Biofilm Activities of Surface Engineered Polycationic Albumin Nanoparticles with Reduced Hemolytic Activity. Macromol. Biosci. 2018, 18, 1800196. 33. Lu, B.; Lu, F.; Ran, L.; Yu, K.; Xiao, Y.; Li, Z.; Dai, F.; Wu, D.; Lan, G. Imidazole-MoleculeCapped Chitosan–Gold Nanocomposites with Enhanced Antimicrobial Activity for Treating Biofilm-Related Infections. J. Colloid Interface Sci. 2018, 531, 269–281. 34. Burdușel, A.-C.; Gherasim, O.; Grumezescu, A. M.; Mogoantă, L.; Ficai, A.; Andronescu, E. Biomedical Applications of Silver Nanoparticles: An Up-to-Date Overview. Nanomaterials 2018, 8, 681. 35. Alvarado-Gomez, E.; Martínez-Castañon, G.; Sanchez-Sanchez, R.; Ganem-Rondero, A.; Yacaman, M. J.; Martinez-Gutierrez, F. Evaluation of Anti-Biofilm and Cytotoxic Effect of a Gel Formulation with Pluronic F-127 and Silver Nanoparticles as a Potential Treatment for Skin Wounds. Mater. Sci. Eng. C. 2018, 92, 621–630. 36. Sinsinwar, S.; Sarkar, M. K.; Suriya, K. R.; Nithyanand, P.; Vadivel, V. Use of Agricultural Waste (Coconut Shell) for the Synthesis of Silver Nanoparticles and Evaluation of Their Antibacterial Activity Against Selected Human Pathogens. Microb. Pathog. 2018, 124, 30–37. 37. Dutra-Correa, M.; Leite, A. A. B. V.; de Cara, S. P. H. M.; Diniz, I. M. A.; Marques, M. M.; Suffredini, I. B.; Fernandes, M. S.; Toma, S. H.; Araki, K.; Medeiros, I. S. Antibacterial Effects and Cytotoxicity of an Adhesive Containing Low Concentration of Silver Nanoparticles. J. Dent. 2018, 77, 66–71. 38. Ramasamy, M.; Lee, J. H.; Lee, J. Potent Antimicrobial and Antibiofilm Activities of Bacteriogenically Synthesized Gold-Silver Nanoparticles against Pathogenic Bacteria and Their Physiochemical Characterizations. J. Biomater. Appl. 2016, 31, 366–378.


39. Rajkumari, J.; Meena, H.; Gangatharan, M.; Busi, S. Green Synthesis of Anisotropic Gold Nanoparticles Using Hordenine and Their Antibiofilm Efficacy Against Pseudomonas Aeruginosa. IET Nanobiotechnol. 2017, 11, 987–994. 40. Prabhawathi, V.; Sivakumar, P. M.; Boobalan, T.; Manohar, C. M.; Doble, M. Design of Antimicrobial Polycaprolactam Nanocomposite by Immobilizing Subtilisin Conjugated Au/Ag Core-Shell Nanoparticles for Biomedical Applications. Mater. Sci. Eng. C. Mater. Biol. Appl. 2019, 94, 656–665. 41. Pakseresht, S.; Alogaili, A. W. M.; Akbulut, H.; Placha, D.; Pazdziora, E.; Klushina, D.; Konvičková, Z.; Kratošová, G.; Holešová, S.; Martynková, G. S. Silver/Chitosan Antimicrobial Nanocomposites Coating for Medical Devices: Comparison of Nanofiller Effect Prepared via Chemical Reduction and Biosynthesis. J. Nanosci. Nanotechnol. 2019, 19, 2938–2942. 42. Ohko, Y.; Nagao, Y.; Okano, K.; Sugiura, N.; Fukuda, A.; Yang, Y.; Negishi, N.; Takeuchi, M.; Hanada, S. Prevention of Phormidium Tenue Biofilm Formation by TiO2 Photocatalysis. Microbes Environ. 2009, 24, 241–245. 43. Pal, S.; Tak, Y. K.; Song, J. M. Does the Antibacterial Activity of Silver Nanoparticles Depend on the Shape of the Nanoparticle? A Study of the Gram-Negative Bacterium Escherichia coli. J. Biol. Chem. 2015, 73, 1712–1720. 44. El Badawy, A. M.; Silva, R. G.; Morris, B.; Scheckel, K. G.; Suidan, M. T.; Tolaymat, T. M. Surface Charge-Dependent Toxicity of Silver Nanoparticles. Environ. Sci. Technol. 2011, 45, 283–287. 45. Sondi, I.; Salopek-Sondi, B. Silver Nanoparticles as Antimicrobial Agent: A Case Study on E. coli as a Model for Gram-Negative Bacteria. J. Colloid Interface Sci. 2004, 275, 177–182. 46. Yun, H.; Kim, J. D.; Choi, H. C.; Lee, C. W. Antibacterial Activity of CNT-Ag and GO-Ag Nanocomposites Against Gram-Negative and Gram-Positive Bacteria. Bull. Korean Chem. Soc. 2013, 34, 3261. 47. Iavicoli, I.; Fontana, L.; Leso, V.; Bergamaschi, A. The Effects of Nanomaterials as Endocrine Disruptors. Int. J. Mol. Sci. 2013, 14, 16732–16801. 48. Ansari, M.; Khan, H.; Khan, A.; Cameotra, S.; Alzohairy, M. Anti-Biofilm Efficacy of Silver Nanoparticles against MRSA and MRSE Isolated from Wounds in a Tertiary Care Hospital. Indian J. Med. Microbiol. 2015, 33, 101–109. 49. Dubey, P.; Matai, I.; Kumar, S. U.; Sachdev, A.; Bhushan, B.; Gopinath, P. Perturbation of Cellular Mechanistic System by Silver Nanoparticle Toxicity: Cytotoxic, Genotoxic and Epigenetic Potentials. Adv. Colloid Interface Sci. 2015, 221, 4–21. 50. Yu, Q.; Li, J.; Zhang, Y.; Wang, Y.; Liu, L.; Li, M. Inhibition of Gold Nanoparticles (AuNPs) on Pathogenic Biofilm Formation and Invasion to Host Cells. Sci. Rep. 2016, 6, 26667. 51. Brown, A. N.; Smith, K.; Samuels, T. A.; Lu, J.; Obare, S. O.; Scott, M. E. Nanoparticles Functionalized with Ampicillin Destroy Multiple-Antibiotic-Resistant Isolates of Pseudomonas aeruginosa and Enterobacter aerogenes and Methicillin-Resistant Staphylococcus aureus. Appl. Environ. Microbiol. 2012, 78, 2768–2774. 52. Chen, W. Y.; Lin, J. Y.; Chen, W. J.; Luo, L.; Wei-Guang Diau, E.; Chen, Y. C. Functional Gold Nanoclusters as Antimicrobial Agents for Antibiotic-Resistant Bacteria. Nanomedicine 2010, 5, 755–764.


53. Nevius, B. A.; Chen, Y. P.; Ferry, J. L.; Decho, A. W. Surface-Functionalization Effects on Uptake of Fluorescent Polystyrene Nanoparticles by Model Biofilms. Ecotoxicology 2012, 21, 2205–2213. 54. Lichter, J. A.; Rubner, M. F. Polyelectrolyte Multilayers with Intrinsic Antimicrobial Functionality: The Importance of Mobile Polycations. Langmuir 2009, 25, 7686–7694. 55. Park, H.; Park, H. J.; Kim, J. A.; Lee, S. H.; Kim, J. H.; Yoon, J.; Park, T. H. Inactivation of Pseudomonas aeruginosa PA01 Biofilms by Hyperthermia Using Superparamagnetic Nanoparticles. J. Microbiol. Methods 2011, 84, 41–45. 56. Khan, S.; Alam, F.; Azam, A.; Khan, A. U. Gold Nanoparticles Enhance Methylene BlueInduced Photodynamic Therapy: A Novel Therapeutic Approach to Inhibit Candida Albicans Biofilm. Int. J. Nanomed. 2012, 7, 3245–3257. 57. Shrestha, A.; Kishen, A. Antibiofilm Efficacy of Photosensitizer-Functionalized Bioactive Nanoparticles on Multispecies Biofilm. J. Endod. 2014, 40, 1604–1610. 58. Ferro, S.; Ricchelli, F.; Mancini, G.; Tognon, G.; Jori, G. Inactivation of Methicillin-Resistant Staphylococcus aureus (MRSA) by Liposome-Delivered Photosensitising Agents. J. Photochem. Photobiol. B Biol. 2006, 83, 98–104. 59. Viola, G. M.; Darouiche, R. O. Cardiovascular Implantable Device Infections. Curr. Infec. Dis. Rep. 2011, 13, 333–342. 60. Liang, S. Y.; Beekmann, S. E.; Polgreen, P. M.; Warren, D. K. Current Management of Cardiac Implantable Electronic Device Infections by Infectious Disease Specialists. Clin. Infect. Dis. 2016, 63, 1072–1075. 61. Vongpatanasin, W.; Hillis, L. D.; Lange, R. A. Prosthetic Heart Valves. N. Engl. J. Med. 1996, 335, 407–416. 62. Thornton, J. W.; Argenta, L. C.; McClatchey, K. D.; Marks, M. W. Studies on the Endogenous Flora of the Human Breast. Ann. Plast. Surg. 1988, 20, 39–42. 63. Burkhardt, B. R.; Fried, M.; Schnur, P. L.; Tofield, J. J. Capsules, Infection, and Intraluminal Antibiotics. Plast. Reconstr. Surg. 1981, 68, 43–49. 64. Pajkos, A.; Deva, A. K.; Vickery, K.; Cope, C.; Chang, L.; Cossart, Y. E. Detection of Subclinical Infection in Significant Breast Implant Capsules. Plast. Reconstr. Surg. 2003, 111, 1605–1611. 65. Nair, N.; Pilakka-Kanthikeel, S.; Saiyed, Z.; Yndart, A.; Nair, M. Silicone Nanoparticles Do Not Induce Immune Responses by Naive Human Peripheral Blood Mononuclear Cells: Implications in Breast Implants. Plast. Reconstr. Surg. 2012, 130, 128–137. 66. Mihu, M. R.; Cabral, V.; Pattabhi, R.; Tar, M. T.; Davies, K. P.; Friedman, A. J.; Martinez, L. R.; Nosanchuk, J. D. Sustained Nitric Oxide-Releasing Nanoparticles Interfere with Methicillin-Resistant Staphylococcus aureus Adhesion and Biofilm Formation in a Rat Central Venous Catheter Model. Antimicrob. Agents Chemother. 2017, 61, 2020. 67. de Freitas, L. M.; Calixto, G. M. F.; Chorilli, M.; Giusti, J. S. M.; Bagnato, V. S.; Soukos, N. S.; Amiji, M. M.; Fontana, C. R. Polymeric Nanoparticle-Based Photodynamic Therapy for Chronic Periodontitis in Vivo. Int. J. Mol. Sci. 2016, 17, 769. 68. Elizabeth, E.; Baranwal, G.; Krishnan, A. G.; Menon, D.; Nair, M. ZnO Nanoparticle Incorporated Nanostructured Metallic Titanium for Increased Mesenchymal Stem Cell Response and Antibacterial Activity. Nanotechnology 2014, 25, 115101. 139 Rathinam and Sani; Introduction to Biofilm Engineering ACS Symposium Series; American Chemical Society: Washington, DC, 2019.

69. De Giglio, E.; Trapani, A.; Cafagna, D.; Ferretti, C.; Iatta, R.; Cometa, S.; Ceci, E.; Romanelli, A.; Mattioli-Belmonte, M. Ciprofloxacin-Loaded Chitosan Nanoparticles as Titanium Coatings: A Valuable Strategy to Prevent Implant-Associated Infections. Nano Biomed. Eng. 2012, 4, 163–169. 70. Hazer, D. B.; Sakar, M.; Dere, Y.; Altinkanat, G.; Ziyal, M. I.; Hazer, B. Polymer-Based Silver Nanoparticle Coated Pedicle Screws Inhibits Biofilm Formation-A Novel Experimental Model in Rabbits. Glob. Spine J. 2016, 36, 1582883. 71. Angelina, J. T. T.; Ganesan, S.; Panicker, T. M. R.; Narayani, R.; Paul Korath, M.; Jagadeesan, K. Pulsed Laser Deposition of Silver Nanoparticles on Prosthetic Heart Valve Material to Prevent Bacterial Infection. Mater. Technol. 2017, 32, 148–155. 72. Li, Y.; Leung, P.; Yao, L.; Song, Q. W.; Newton, E. Antimicrobial Effect of Surgical Masks Coated with Nanoparticles. J. Hosp. Infect. 2006, 62, 58–63. 73. Giri, K.; Rivas Yepes, L.; Duncan, B.; Kolumam Parameswaran, P.; Yan, B.; Jiang, Y.; Bilska, M.; Moyano, D. F.; Thompson, M. A.; Rotello, V. M.; Prakash, Y. S. Targeting Bacterial Biofilms via Surface Engineering of Gold Nanoparticles. RSC Adv. 2015, 5, 105551–105559. 74. Magalhães, A. P. R.; Santos, L. B.; Lopes, L. G.; Estrela, C. R. de A.; Estrela, C.; Torres, É. M.; Bakuzis, A. F.; Cardoso, P. C.; Carrião, M. S. Nanosilver Application in Dental Cements. ISRN Nanotechnol. 2012, 6. 75. Zhao, L.; Wang, H.; Huo, K.; Cui, L.; Zhang, W.; Ni, H.; Zhang, Y.; Wu, Z.; Chu, P. K. Antibacterial Nano-Structured Titania Coating Incorporated with Silver Nanoparticles. Biomaterials 2011, 32, 5706–5716. 76. Qu, W.; Hooymans, J. M. M.; Qiu, J.; De-Bont, N.; Gelling, O. J.; Van Der Mei, H. C.; Busscher, H. J. Nonadhesive, Silica Nanoparticles-Based Brush-Coated Contact Lens CasesCompromising Between Ease of Cleaning and Microbial Transmission to Contact Lenses. J. Biomed. Mater. Res.-Part B Appl. Biomater. 2013, 101, 640–647. 77. Tuby, R.; Gutfreund, S.; Perelshtein, I.; Mircus, G.; Ehrenberg, M.; Mimouni, M.; Gedanken, A.; Bahar, I. Fabrication of a Stable and Efficient Antibacterial Nanocoating of Zn-CuO on Contact Lenses. Chem. Nano. Mat. 2016, 2, 547–551.


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