title: Strategies for antimicrobial drug delivery to biofilm.
abstract: Biofilms are formed by the attachment of single or mixed microbial communities to a variety of biological and/or synthetic surfaces. Biofilm micro-organisms benefit from many advantages of the polymicrobial environment including increased resistance against antimicrobials and protection against the host organism's defence mechanisms. These benefits stem from a number of structural and physiological differences between planktonic and biofilm-resident microbes, but two main factors are the presence of extracellular polymeric substances (EPS) and quorum sensing communication. Once formed, biofilms begin to synthesise EPS, a complex viscous matrix composed of a variety of macromolecules including proteins, lipids and polysaccharides. In terms of drug delivery strategies, it is the EPS that presents the greatest barrier to diffusion for drug delivery systems and free antimicrobial agents alike. In addition to EPS synthesis, biofilm-based micro-organisms can also produce small, diffusible signalling molecules involved in cell density-dependent intercellular communication, or quorum sensing. Not only does quorum sensing allow microbes to detect critical cell density numbers, but it also permits co-ordinated behaviour within the biofilm, such as iron chelation and defensive antibiotic activities. Against this backdrop of microbial defence and cell density-specific communication, a variety of drug delivery systems have been developed to deliver antimicrobial agents and antibiotics to extracellular and/or intracellular targets, or more recently, to interfere with the specific mechanisms of quorum sensing. Successful delivery strategies have employed lipidic and polymeric-based formulations such as liposomes and cyclodextrins respectively, in addition to inorganic carriers e.g. metal nanoparticles. This review will examine a range of drug delivery systems and their application to biofilm delivery, as well as pharmaceutical formulations with innate antimicrobial properties such as silver nanoparticles and microemulsions.
authors.forename: Claire
authors.initials: C
authors.lastname: Martin
authors.forename: Wan Li
authors.initials: WL
authors.lastname: Low
authors.forename: Abhishek
authors.initials: A
authors.lastname: Gupta
authors.forename: Mohd Cairul Iqbal Mohd
authors.initials: MC
authors.lastname: Amin
authors.forename: Iza
authors.initials: I
authors.lastname: Radecka
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Britland
authors.forename: Prem
authors.initials: P
authors.lastname: Raj
authors.affiliation: Department of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton, WV1 1LY, United Kingdom. Claire.martin2@wlv.ac.uk.
authors.forename: Ken M A
authors.initials: KM
authors.lastname: Kenward
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002450:Cell Communication / Q000502:physiology; D002452:Cell Count; D016503:Drug Delivery Systems; D004352:Drug Resistance, Microbial; D004655:Emulsions; D006801:Humans; D053768:Metal Nanoparticles; D053038:Quorum Sensing / Q000502:physiology
chemical_list: D000890:Anti-Infective Agents; D004655:Emulsions