Stimuli-responsive solid lipid nanoparticles for targeted drug delivery in biofilm-resistant infections: advances and...

The aim of this study was to explore the design, mechanisms, and therapeutic potential of stimuli-responsive solid lipid nanoparticles (SLNs) for biofilm-targeted drug delivery, highlighting recent advances and future directions.

Biofilm-associated infections present a significant challenge in healthcare owing to the protective extracellular matrix (EPS), which restricts antibiotic penetration and promotes biofilm resistance. SLNs have emerged as promising drug delivery systems owing to their biocompatibility, drug-loading capacity, and controlled release characteristics. Stimuli-responsive SLNs, which release drugs in response to environmental triggers such as pH, enzymes, temperature, and light, offer enhanced targeting and improved drug delivery efficiency to biofilms. Notable preclinical examples include ciprofloxacin, vancomycin, rifampin and tobramycin-all of which have been formulated in SLNs/nanostructured lipid carriers with improved antibiofilm activity versus free drug in vitro and in some in vivo models.

Preclinical studies have demonstrated that SLN-based formulations significantly reduce biofilm biomass and enhance antibiotic efficacy against biofilm-associated infections. Stimuli-responsive SLNs facilitate deeper penetration of biofilms, thereby improving drug retention and therapeutic outcomes. However, challenges such as limited drug-loading capacity, stability, manufacturability, and clinical translation remain significant barriers to the widespread adoption of SLN-based therapies.

Stimuli-responsive SLNs represent a promising strategy for overcoming biofilm resistance and enhancing antibiotic delivery. Although preclinical data are promising, addressing formulation challenges and improving scalability are essential for successful clinical translation. Further research on optimizing SLN design and understanding biofilm interactions will be critical for advancing SLN-based therapies for biofilm-associated infections.