Nanoparticle-Based Drug Delivery Systems for Biofilm Infections

Biofilm-associated infections pose a formidable challenge to conventional antimicrobial therapies owing to the protective extracellular polymeric substance (EPS) matrix, heterogeneity of the microbial community and altered metabolic states within the biofilm. Nanoparticle-based delivery systems offer a multifaceted solution by combining targeted penetration, controlled release and multifunctional payloads. Liposomal carriers, polymeric micelles and inorganic nanovehicles can be engineered for size (<200 nm), surface charge and ligand functionalisation to enhance diffusion through the EPS. Stimuli-responsive constructs release antibiotics or enzymatic agents in response to pH shifts, temperature changes, ultrasound or light, thereby concentrating activity at the infection site while minimising systemic toxicity. Hybrid platforms that co-deliver matrix-degrading enzymes, quorum-sensing inhibitors or reactive oxygen species generators alongside conventional antibiotics have demonstrated superior eradication of mature biofilms in preclinical models. Despite promising in vitro and in vivo results, translation to clinical practice requires overcoming hurdles in large-scale manufacturing, long-term stability, biocompatibility and regulatory approval.

Research from Nature Portfolio

Recent studies have introduced thermoresponsive polymeric nanoparticles encapsulating β-lactam antibiotics. Upon local heating to 42 °C, the carriers transition from a collapsed to a swollen state, releasing drug deep within Pseudomonas aeruginosa biofilms and achieving over 90 percent eradication in murine wound models. Another innovative platform employs upconversion nanoparticles conjugated with DNase I and a broad-spectrum antibiotic; near-infrared irradiation triggers simultaneous EPS degradation and antibiotic release, resulting in substantial reduction of mature biofilms formed by both Gram-positive and Gram-negative pathogens. A third approach utilises pH-sensitive exosome-mimetic vesicles loaded with quorum-sensing inhibitors. These vesicles preferentially accumulate in the acidic microenvironment of biofilms, disrupt cell-to-cell communication and lower bacterial burden by more than 80 percent in implant-associated infection models.

Nanoparticle-Based Drug Delivery Systems for Biofilm Infections publication trend

The graph below shows the total number of articles in nanoparticle-based drug delivery systems for biofilm infections across all publications each year (not limited to Nature Index journals).

Technical terms

Biofilm: A surface-attached microbial community embedded in a self-produced matrix exhibiting enhanced tolerance to antimicrobials.

Extracellular polymeric substance (EPS): The gel-like matrix of polysaccharides, proteins and nucleic acids that encases biofilm cells.

Liposome: A spherical vesicle of one or more phospholipid bilayers capable of encapsulating both hydrophilic and hydrophobic agents.

Stimuli-responsive nanoparticle: A nanocarrier designed to release its payload upon encountering specific triggers such as pH, temperature, ultrasound or light.

Quorum sensing inhibitor: A molecule that interferes with bacterial communication pathways, impeding coordinated biofilm formation.

References

1. Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery. npj Antimicrobials and Resistance (2025).
2. Monitoring silica core@shell nanoparticle‐bacterial film interactions using the multi‐parametric surface plasmon resonance technique. Smart Medicine (2023).
3. Non disseminative nano-strategy against in vivo Staphylococcus aureus biofilms. npj Biofilms and Microbiomes (2023).
4. Recent Nanotechnology Approaches for Prevention and Treatment of Biofilm‐Associated Infections on Medical Devices. BioMed Research International (2016).