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.

Traditional synthetic techniques for silver nanoparticles synthesis involve toxic chemicals that are harmful to humans as well as the environment. The green chemistry method for nanoparticle synthesis is rapid, eco-friendly, and less toxic as compared to the traditional methods. In the present research, we synthesized silver nanoparticles employing a green chemistry approach from Parthenium hysterophorus leaf extract. The optimized parthenium silver nanoparticles (PrSNPs) had a mean particle size of 187.87 ± 4.89 nm with a narrow size distribution of 0.226 ± 0.009 and surface charge −34 ± 3.12 mV, respectively. The physicochemical characterization of optimized SNPs was done by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Moreover, the transmission electron microscopy (TEM) analysis indicates the spherical shape of NPs with an average diameter of 20–25 nm. PrSNPs were investigated for in vitro antibacterial, antifungal, anti-inflammatory, and antioxidant properties, and showed excellent profiles. The cytotoxic activity was analyzed against two cancer cell lines, i.e., B16F10 and HepG2 for 24 h and 48 h. PrSNPs proved to be an excellent anticancer agent. These PrSNPs were also employed for the treatment of wastewater by monitoring the E. coli count, and it turned out to be reduced by 58%; hence these NPs could be used for disinfecting water. Hence, we can propose that PrSNPs could be a suitable candidate as an antimicrobial, antioxidant, anti-inflammatory, and antitumor agent for the treatment of several ailments.

Intravesical drug delivery is a direct drug delivery approach for the treatment of various bladder diseases. The human urinary bladder has distinctive anatomy, making it an effective barrier against any toxic agent seeking entry into the bloodstream. This screening function of the bladder derives from the structure of the urothelium, which acts as a semi-permeable barrier. However, various diseases related to the urinary bladder, such as hyperactive bladder syndrome, interstitial cystitis, cancer, urinary obstructions, or urinary tract infections, can alter the bladder’s natural function. Consequently, the intravesical route of drug delivery can effectively treat such diseases as it offers site-specific drug action with minimum side effects. Intravesical drug delivery is the direct instillation of medicinal drugs into the urinary bladder via a urethral catheter. However, there are some limitations to this method of drug delivery, including the risk of washout of the therapeutic agents with frequent urination. Moreover, due to the limited permeability of the urinary bladder walls, the therapeutic agents are diluted before the process of permeation, and consequently, their efficiency is compromised. Therefore, various types of nanomaterial-based delivery systems are being employed in intravesical drug delivery to enhance the drug penetration and retention at the targeted site. This review article covers the various nanomaterials used for intravesical drug delivery and future aspects of these nanomaterials for intravesical drug delivery.

Conventional antibiotic therapies often fail to eradicate bacterial biofilms due to limited penetration, altered microenvironments, and the presence of persister cells, contributing to persistent and recurrent infections. As a result,the growing threat of antibiotic-resistant bacteria, particularly those forming biofilms, underscores the urgent need for alternative therapeutic strategies. Lipid-based drug delivery systems have emerged as effective nanocarriers for antimicrobials, offering a promising strategy to combat bacterial biofilms due to their biomimetic properties, biocompatibility, and ability to navigate the complex physical, chemical, and biological barriers posed by biofilms. In this study, we compared liquid crystal nanoparticles (LCNPs) and liposomes as delivery systems for gentamicin (GEN) against Escherichia coli (E. coli) (ATCC 25922 and ATCC 35218) in both planktonic and biofilm forms. Transmission electron microscopy analysis confirmed the particle size of GEN-loaded LCNPs (~ 200 nm) and GEN-loaded liposomes (~ 160 nm), with cubic-shaped LCNPs and lipid bilayer-structured liposomes which remained stable over three weeks at 4ºC. Loading GEN into lipid-based nanoparticles resulted in a two-fold reduction in minimum inhibitory concentration values, without significantly altering the minimum bactericidal concentration. Notably, GEN-LCNPs led to a significant fourfold (for E. coli ATCC 25922) and threefold (for E. coli ATCC 35218) reduction in inhibitory concentrations in biofilm states compared to unformulated GEN, achieving a minimum biofilm inhibitory concentration (MBIC) of 50 μg/mL and 100 μg/mL (P < 0.0001), respectively. In contrast, liposomes showed only a twofold reduction in MBIC values (100–150 μg/mL) for both bacterial biofilms. GEN-loaded LCNPs also reduced the E. coli ATCC 25922 colony-forming unit count by 5000-fold and 4000-fold, while liposomes with similar particle size did not significantly improve GEN’s antimicrobial activity. Moreover, LCNPs improved GEN efficacy regardless of particle size or Pluronic^® concentration. In conclusion, our findings suggest that GEN-loaded LCNPs demonstrated superior antimicrobial efficacy against E. coli biofilms compared to liposomes, highlighting their potential as effective nanocarriers for combating antibiotic-resistant infections. Graphical Abstract