Stimuli-responsive polymers for antimicrobial therapy: drug targeting, contact-killing surfaces and competitive release

ABSTRACT

Introduction: Polymers can be designed to modify their features as a function of the level and nature of the surrounding microorganisms. Such responsive polymers can endow drug delivery systems and drug-medical device combination products with improved performance against intracellular infections and biofilms.

Areas covered: Knowledge on microorganism growth environment outside and inside cells and formation of biofilm communities on biological and synthetic surfaces, together with advances in materials science and drug delivery are prompting strategies with improved efficacy and safety compared to traditional systemic administration of antimicrobial agents. This review deals with antimicrobial strategies that rely on: (i) polymers that disintegrate or undergo phase-transitions in response to changes in enzymes, pH and pO₂ associated to microorganism growth; (ii) stimuli-responsive polymers that expose contact-killing groups when microorganisms try to adhere; and (iii) bioinspired polymers that recognize microorganisms for triggered (competitive/affinity-driven) drug release.

Expert opinion: Prophylaxis and treatment of infections may benefit from polymers that are responsive to the unique changes that microbial growth causes in the surrounding environment or that even recognize the microorganism itself or its quorum sensing signals. These polymers may offer novel tools for the design of macrophage-, bacteria- and/or biofilm-targeted nanocarriers as well as of medical devices with switchable antibiofouling properties.

KEYWORDS:

• Antibiofilm
• antimicrobial drug delivery
• contact-killing surfaces
• intracellular infections
• microorganism-triggered release
• medical device
• nanocarrier

Article highlights

• Intracellular infections and healthcare-related biofilms are strong challenges for antimicrobial therapy.

• Drug delivery systems and medical devices can be designed to release antimicrobial agents only when microorganisms are present.

• Poly(lactic-co-glycolic) acid and polyphosphoesters exhibit distinct degradation rates in the presence of microorganisms.

• Enzyme-responsive nanocarriers can selectively release the drug inside bacteria-containing macrophages.

• Enzyme-degradable wound dressings tune drug release rate as a function of microbial growth.

• pH- and temperature-responsive polymers are suitable for self-defensive coatings that release an antimicrobial agent or that exhibit contact-killing surfaces in the infection environment.

• Medical devices functionalized with ergosterol or cyclodextrins can regulate the release of antibacterial and antifungal agents by means of competitive mechanisms.

This box summarizes key points contained in the article.

Declaration of interests

This work was financially supported by MINECO (SAF2014-52632-R) Spain and FEDER. CA García-González acknowledges MINECO for the financial support through the Ramon y Cajal Programme (RYC-2014-15239). The authors also acknowledge the ‘Galician Network for Colorectal Cancer Research (REGICC)’ (Ref. R2014/039) funded by the Xunta de Galicia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.