The opportunistic bacteria growing in biofilms play a decisive role in the pathogenesis of chronic infectious diseases. Biofilm-dwelling bacteria behave differently than planktonic bacteria and are likely to increase resistance and tolerance to antimicrobial therapeutics. Antimicrobial adjuvants have emerged as a promising strategy to combat antimicrobial resistance (AMR) and restore the efficacy of existing antibiotics. A combination of antibiotics and potential antimicrobial adjuvants, (e.g., extracellular polymeric substance (EPS)-degrading enzymes and quorum sensing inhibitors (QSI) can improve the effects of antibiotics and potentially reduce bacterial resistance). In addition, encapsulation of antimicrobials within nanoparticulate systems can improve their stability and their delivery into biofilms. Lipid nanocarriers (LNCs) have been established as having the potential to improve the efficacy of existing antibiotics in combination with antimicrobial adjuvants. Among them, liquid crystal nanoparticles (LCNPs), liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) are promising due to their superior properties compared to traditional formulations, including their greater biocompatibility, higher drug loading capacity, drug protection from chemical or enzymatic degradation, controlled drug release, targeted delivery, ease of preparation, and scale-up feasibility. This article reviews the recent advances in developing various LNCs to co-deliver some well-studied antimicrobial adjuvants combined with antibiotics from different classes. The efficacy of various combination treatments is compared against bacterial biofilms, and synergistic therapeutics that deserve further investigation are also highlighted. This review identifies promising LNCs for the delivery of combination therapies that are in recent development. It discusses how LNC-enabled co-delivery of antibiotics and adjuvants can advance current clinical antimicrobial treatments, leading to innovative products, enabling the reuse of antibiotics, and providing opportunities for saving millions of lives from bacterial infections.

Biofilm-associated infections present a major therapeutic challenge due to their intrinsic tolerance to antibiotics and the protective extracellular polymeric substance (EPS) matrix. In this study, liquid crystalline nanoparticles (LCNPs) were developed as a co-delivery platform for gentamicin (GEN) and the quorum sensing inhibitor cinnamaldehyde (CIN) to enhance antibiofilm efficacy against Pseudomonas aeruginosa. LCNPs were successfully fabricated using a hydrotrope dilution method, producing nanoparticles with mean diameters of ~200–230 nm and negative surface charge. Co-loading of GEN and CIN resulted in high encapsulation efficiency, particularly for CIN (~90%), although increased hydrophobic loading influenced structural organisation and stability. Release studies demonstrated distinct drug behaviours, with GEN exhibiting rapid diffusion-controlled release, while CIN showed sustained non-Fickian release governed by lipid partitioning. Antimicrobial evaluation demonstrated that LCNP encapsulation enhanced GEN activity against planktonic bacteria compared with unformulated drug. CIN significantly inhibited biofilm formation at sub-inhibitory concentrations, reducing biofilm biomass by approximately 40–60%, consistent with quorum sensing disruption. LCNP-mediated co-delivery of GEN and CIN, particularly at a 1:100 ratio, produced substantially enhanced antibiofilm activity, achieving approximately 5-log reductions in viable biofilm-associated bacteria compared with unformulated combinations and monotherapies. The enhanced efficacy is likely attributed to improved penetration into the biofilm matrix and coordinated delivery of both agents. Overall, this study demonstrates that LCNP-mediated co-delivery of antibiotics and quorum sensing inhibitors represents a promising strategy for overcoming biofilm-associated antimicrobial resistance.