Elsevier

European Polymer Journal

Volume 65, April 2015, Pages 46-62
European Polymer Journal

Feature Article
The roadmap of antimicrobial polymeric materials in macromolecular nanotechnology

https://doi.org/10.1016/j.eurpolymj.2015.01.030Get rights and content

Highlights

  • Self-assembled amphiphilic polymers exhibit superior antimicrobial activity.

  • Drug-loaded nanomaterials extend the blood circulation time to reach the target sites.

  • Antimicrobial nanocomposites are of great interest in many practical applications.

  • Nanotexturation of polymeric surfaces can effectively reduce bacterial adhesion.

Abstract

Antimicrobial strategies combining polymer science and nanotechnology have attracted tremendous interest in the last decade because of their great potential in many applications. This feature article presents our vision for the continuous progress in this area. Then, its first part has been focused on the different methodologies used to obtain antimicrobial nanomaterials, such as self-assembly, nanoprecipitation, and electrospinning, among others. The surface nanostructuring of polymeric films and its effects on the antimicrobial behavior are briefly described in the second half.

Introduction

The incessant search of humans for healthcare, welfare and safety is undeniable and nowadays microbial infections are a great concern since many of the infectious diseases are reappearing in a more serious manner. One of the main problems associated with these goals is the widespread production, use, and abuse of antibiotics that have contributed to the emergence of multiple drug-resistant infectious organisms, so called superbugs as methicillin or vancomycin-resistant Staphylococcus aureus bacteria (MRSA or VRSA), respectively. As WHO recommends [1], infected people should receive expert care in appropriate facilities. In this sense, safe hospitals with aseptic biomedical devices, clean walls, furniture, clothes and other matters demand antimicrobial systems able to avoid the transmission and the extent of contagious illness. Nowadays, there is a great diversity of commercial products with antimicrobial properties, e.g. air conditioning equipment, freezes, filters, paints, toys, kitchen utensils, towels, paper and so on.

On the other hand, nanotechnology consists of the construction of functional materials, devices, and systems with novel and valuable properties through the control, manipulation and organization of matter at the nanometer length scale (from 1 to 100 nm). Nanomaterials might frequently exhibit different and/or enhanced physical and chemical behaviors with respect to those proved at the bulk, fact that has converted to nanotechnology in an exponentially growing industry. Then, where is the fear on nanoscience and nanotechnology? People usually think in the incorporation of metallic or inorganic nanoparticles, some of them being probably toxic. The effect on the body of these nanosized particles is difficult to be predicted and, at present, it is not completely understood. Besides, people are unaware of their long-term effects over health, well-being and environment. All these reasons make nanomaterials to provide sometimes insecurity to the population, in general, and to the scientific community, in particular. In this regard, nanomaterials based on polymers and, specifically, antimicrobial polymeric materials due to their intrinsic characteristics surpass the created expectative goals to solve all these problems. Then, polymers are the preferred materials for many applications, such as food packaging, biomedical devices or water purification systems because of their excellent processing characteristics and their variety of mechanical properties. These antimicrobial polymeric materials are divided into four categories [2]: (i) those systems presenting antimicrobial activity by themselves; (ii) polymers chemically modified to confer this specific activity; (iii) polymers blended with organic active compounds with low or high molecular weights (i.e. biocides or antimicrobial polymers); and (iv) polymers blended with inorganic active substances. Accordingly, the aim of this present article is the development of polymeric materials with antimicrobial activity [2], [3] by using the nanoscience and nanotechnology fields for targeting the different challenges in the treatment of infectious diseases [4]. The first part of the article focuses the attention on the methodologies with capability of leading to antimicrobial polymeric nanomaterials. This section is, then, divided in three different approaches: the first one based on antimicrobial polymeric materials and, particularly, their self-assembled polymer nanostructures that offer advantages over the small molecules of antibiotics and are, in principle, less susceptible to development of resistance by bacteria. This last feature is because those molecules destroy bacterial membranes instead of interacting with the metabolic process of the microorganisms, the opportunity for mutation being in this way reduced. The second assumption is related to polymeric particles that are versatile and effective carriers in drug delivery since they can be designed in a variety of morphologies and functionalities. Then, they offer the possibility of generating smart systems. Most of methodologies employed in this section are common to those used in unloaded polymers. The last one corresponds with the incorporation of antimicrobial inorganic nanoparticles into a polymeric matrix and the subsequent formation of polymeric nanocomposites. This hypothesis has undergone an important growth in the development of antimicrobial materials. On the other hand, the second part of the article will address the creation of micro and nanostructuration on polymeric surfaces, topic that is nowadays attracting an increasing attention in order to reduce the bacterial adhesion. To conclude, some considerations will be presented on the future evolution of this important field.

Section snippets

Self-assembly

Amphiphilic polymers can develop nanostructures, such as polymeric micelles with sizes ranging the nanoscale by their self-association in water above the critical micelle concentration (CMC). This fact represents one of the most versatile nanotechnology tools to enhance the aqueous solubility of poorly-water soluble substances, as will be described below (Section 1.2).

Polycations and their self-assembly are one of the most generally studied systems to combat infections within the antimicrobial

Effect of nanotextured polymer surfaces on antimicrobial activity

As described above the chemical modification of the material surface is widely used not only to inhibit the bacterial growth but also to prevent the biofilm formation. Nevertheless, it is accepted that the suppression of the bacterial adhesion is the most effective way to fight against bacterial biofilm. Chemical modification presents, however, several drawbacks such as the loss of efficiency over time or once the drug is released. Recently, attention has been also moved toward designing the

The roadmap of antimicrobial polymeric materials in nanotechnology

The nanoscience and nanotechnology are tools to design, understand, create, and manipulate matter at the nanoscale, in the present situation, antimicrobial polymeric materials. As shown, there are different methodologies to achieve these aimed materials, such as self-assembly of polymers, emulsion-evaporation, precipitation, electrospinning, spray, gelation, polymerization, blend process or the nanostructuration of surfaces. Indeed, these technologies can be used with antimicrobial polymers or

Concluding remarks

Herein we have presented some of the possibilities that nanoscience and nanotechnology offer for antimicrobial polymeric materials expansion. Like in other fields, nanotechnology is enormously contributing to the development of novel treatments and methodologies more efficient and safe to fight against microbial infections. Nowadays the emergence of antibiotic resistance as well as other problems associated with complications in immunodeficient patients or cancer treatments create new

Acknowledgements

We thank the financial support of MINECO (Project MAT2010-17016 and MAT2013-47902-C2-1-R) and A. Muñoz-Bonilla thanks MINECO for her Ramon y Cajal contract.

A. Muñoz-Bonilla obtained in 2006 the PhD in Chemistry “European Doctorate Mention” under the supervision of Dr. M. Fernández-García working at the Institute of Polymer Science and Technology (ICTP-CSIC). During 2005 she carried out a research stay at the University of Warwick, (UK) with Prof. D.M. Haddleton. She conducted in 2007–2008 a postdoc in the Laboratoire de Chimie des Polymères Organiques at the Université de Bordeaux (France) with Dr. J. Rodríguez-Hernández and another postdoctoral

References (125)

  • N. Beyth et al.

    Antibacterial activity of dental composites containing quaternary ammonium polyethylenimine nanoparticles against Streptococcus mutans

    Biomaterials

    (2006)
  • N. Beyth et al.

    Surface antimicrobial activity and biocompatibility of incorporated polyethylenimine nanoparticles

    Biomaterials

    (2008)
  • E.A.O. Farias et al.

    Development and characterization of multilayer films of polyaniline, titanium dioxide and CTAB for potential antimicrobial applications

    Mater Sci Eng: C

    (2014)
  • N. Laugel et al.

    Composite films of polycations and TiO2 nanoparticles with photoinduced superhydrophilicity

    J Colloid Interface Sci

    (2008)
  • G. Mohammadi et al.

    Development of azithromycin–PLGA nanoparticles: physicochemical characterization and antibacterial effect against Salmonella typhi

    Colloids Surf B Biointerfaces

    (2010)
  • G. Mohammadi et al.

    Physicochemical and anti-bacterial performance characterization of clarithromycin nanoparticles as colloidal drug delivery system

    Colloids Surf B Biointerfaces

    (2011)
  • F. Ahsan et al.

    Targeting to macrophages: role of physicochemical properties of particulate carriers—liposomes and microspheres—on the phagocytosis by macrophages

    J Control Release

    (2002)
  • F. Fawaz et al.

    Ciprofloxacin-loaded polyisobutylcyanoacrylate nanoparticles: pharmacokinetics and in vitro antimicrobial activity

    Int J Pharm

    (1998)
  • F. Esmaeili et al.

    Preparation and antibacterial activity evaluation of rifampicin-loaded poly lactide-co-glycolide nanoparticles

    Nanomed Nanotechnol Biol Med

    (2007)
  • U.S. Toti et al.

    Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles

    Biomaterials

    (2011)
  • S. Inphonlek et al.

    Synthesis of poly(methyl methacrylate) core/chitosan-mixed-polyethyleneimine shell nanoparticles and their antibacterial property

    Colloids Surf B Biointerfaces

    (2010)
  • G. Cottarel et al.

    Combination drugs, an emerging option for antibacterial therapy

    Trends Biotechnol

    (2007)
  • W.S. Cheow et al.

    Enhancing encapsulation efficiency of highly water-soluble antibiotic in poly(lactic-co-glycolic acid) nanoparticles: modifications of standard nanoparticle preparation methods

    Colloids Surf Physicochem Eng Aspects

    (2010)
  • K. Dillen et al.

    Factorial design, physicochemical characterisation and activity of ciprofloxacin-PLGA nanoparticles

    Int J Pharm

    (2004)
  • K. Dillen et al.

    Evaluation of ciprofloxacin-loaded Eudragit® RS100 or RL100/PLGA nanoparticles

    Int J Pharm

    (2006)
  • K. Dillen et al.

    Adhesion of PLGA or Eudragit®/PLGA nanoparticles to Staphylococcus and Pseudomonas

    Int J Pharm

    (2008)
  • Z. Ahmad et al.

    Novel chemotherapy for tuberculosis: chemotherapeutic potential of econazole- and moxifloxacin-loaded PLG nanoparticles

    Int J Antimicrob Agents

    (2008)
  • R. Pandey et al.

    Nano-encapsulation of azole antifungals: potential applications to improve oral drug delivery

    Int J Pharm

    (2005)
  • F. Ungaro et al.

    Dry powders based on PLGA nanoparticles for pulmonary delivery of antibiotics: modulation of encapsulation efficiency, release rate and lung deposition pattern by hydrophilic polymers

    J Control Release

    (2012)
  • A. Martinelli et al.

    Release behavior and antibiofilm activity of usnic acid-loaded carboxylated poly(l-lactide) microparticles

    Eur J Pharm Biopharm

    (2014)
  • O. Ozay et al.

    P(4-VP) based nanoparticles and composites with dual action as antimicrobial materials

    Colloids Surf B Biointerfaces

    (2010)
  • X. Li et al.

    Nanoparticles by spray drying using innovative new technology: the Büchi Nano Spray Dryer B-90

    J Control Release

    (2010)
  • K. Kim et al.

    Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds

    J Control Release

    (2004)
  • S.S. Said et al.

    Antimicrobial PLGA ultrafine fibers: interaction with wound bacteria

    Eur J Pharm Biopharm

    (2011)
  • S.S. Said et al.

    Bioburden-responsive antimicrobial PLGA ultrafine fibers for wound healing

    Eur J Pharm Biopharm

    (2012)
  • M. Reise et al.

    Release of metronidazole from electrospun poly(l-lactide-co-d/l-lactide) fibers for local periodontitis treatment

    Dent Mater

    (2012)
  • M. Zamani et al.

    Controlled release of metronidazole benzoate from poly ε-caprolactone electrospun nanofibers for periodontal diseases

    Eur J Pharm Biopharm

    (2010)
  • J.G. Lundin et al.

    Relationship between surface concentration of amphiphilic quaternary ammonium biocides in electrospun polymer fibers and biocidal activity

    React Funct Polym

    (2014)
  • P.N. Coneski et al.

    Lyotropic self-assembly in electrospun biocidal polyurethane nanofibers regulates antimicrobial efficacy

    Polymer

    (2014)
  • S.J. Kim et al.

    Preparation and characterization of antimicrobial polycarbonate nanofibrous membrane

    Eur Polym J

    (2007)
  • K.T. Shalumon et al.

    Sodium alginate/poly(vinyl alcohol)/nano ZnO composite nanofibers for antibacterial wound dressings

    Int J Biol Macromol

    (2011)
  • Q. Shi et al.

    Durable antibacterial Ag/polyacrylonitrile (Ag/PAN) hybrid nanofibers prepared by atmospheric plasma treatment and electrospinning

    Eur Polym J

    (2011)
  • X. Xu et al.

    Biodegradable electrospun poly(l-lactide) fibers containing antibacterial silver nanoparticles

    Eur Polym J

    (2006)
  • C. Bilbao-Sainz et al.

    Solution blow spun poly(lactic acid)/hydroxypropyl methylcellulose nanofibers with antimicrobial properties

    Eur Polym J

    (2014)
  • R. Li et al.

    Preparation and antimicrobial activity of β-cyclodextrin derivative copolymers/cellulose acetate nanofibers

    Chem Eng J

    (2014)
  • C. Dong et al.

    Preparation of antimicrobial cellulose fibers by grafting β-cyclodextrin and inclusion with antibiotics

    Mater Lett

    (2014)
  • Z. Ahmad et al.

    Chemotherapeutic evaluation of alginate nanoparticle-encapsulated azole antifungal and antitubercular drugs against murine tuberculosis

    Nanomed Nanotechnol Biol Med

    (2007)
  • Z. Ahmad et al.

    Corrigendum to “Inhalable alginate nanoparticles as antitubercular drug carriers against experimental tuberculosis” [Int. J. Antimicrob. Agents 2005;26:298–303]

    Int J Antimicrob Agents

    (2010)
  • R. Rajendran et al.

    Development of antimicrobial cotton fabrics using herb loaded nanoparticles

    Carbohydr Polym

    (2013)
  • A.J. Friedman et al.

    Antimicrobial and anti-inflammatory activity of chitosan-alginate nanoparticles: a targeted therapy for cutaneous pathogens

    J Invest Dermatol

    (2013)
  • Cited by (0)

    A. Muñoz-Bonilla obtained in 2006 the PhD in Chemistry “European Doctorate Mention” under the supervision of Dr. M. Fernández-García working at the Institute of Polymer Science and Technology (ICTP-CSIC). During 2005 she carried out a research stay at the University of Warwick, (UK) with Prof. D.M. Haddleton. She conducted in 2007–2008 a postdoc in the Laboratoire de Chimie des Polymères Organiques at the Université de Bordeaux (France) with Dr. J. Rodríguez-Hernández and another postdoctoral stay from 2008 to 2010 at Eindhoven University of Technology (The Netherlands) with Prof. J.P.A. Heuts. She went back to the ICTP-CSIC from 2010 to 2014 focusing her research on the synthesis of complex architectures by controlled polymerization techniques as well as on the preparation of hierarchical structured surfaces. Currently she works as Ramon y Cajal researcher at the Autónoma University of Madrid, where she is involved in magnetic hybrid materials.

    M. Fernández-García obtained the PhD in Chemistry (Complutense University of Madrid) under the supervision of Dr. E.L. Madruga in 1995 working at the Institute of Polymer Science and Technology (ICTP-CSIC). She conducted her postdoctoral work at the National Institute of Standards and Technology (NIST) (Maryland, USA) with Dr. M.Y.M. Chiang during the period 1997–1998. She also performed at short stay in 2000 at Technical University of Clausthal (Germany) with Prof. G. Schmitd-Naake. She was recruited at ICTP-CSIC in 1999. Her main research interest involves the synthesis of new polymers and their structuration at micro and nanoscale as well as their applications as multifunctional materials. She has a wide experience in conventional or controlled radical polymerization, structural and morphological characterization of polymeric systems.

    View full text