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(1) Background: Chronic rhinosinusitis (CRS) is a common chronic inflammation of the nasal mucosa and the paranasal sinuses. The pathogenesis of chronic rhinosinusitis (CRS) is multifactorial and, as of yet, not well understood. (2) Methods: Nasal lavage fluid samples were collected from patients diagnosed with chronic sinusitis with nasal polyposis (CRSwNP) (n = 10) and individuals without sinusitis (control group) (n = 10) who had no nasal complaints. In the present study, we used an untargeted label-free LC-MS/MS mass spectrometric approach combined with bioinformatics and network pathway analysis to compare the changes in the proteomic profiles of the CRSwNP group and the control group. Data from LC-MS/MS underwent univariate and multivariate analyses. (3) Results: The proteomic analyses revealed distinct differences in the abundances of nasal lavage fluid proteins between the CRSwNP and control groups: a total of 234 proteins, 151 up- and 83 down-regulated in CRSwNP. Functional Gene Ontology (GO) analysis showed that dysregulated proteins were involved in airway inflammatory reaction, immune response, and oxidative stress. The biomarkers were evaluated using the Receiver Operating Characteristic (ROC) curve; an Area Under the Curve (AUC) of 0.999 (95% CI) identified potential biomarkers between the CRSwNP and control group. EMILIN-3 and RAB11-binding protein RELCH were down-regulated, and Macrophage migration inhibitory factor and deoxyribonuclease-1 were up-regulated, in CRSwNP compared to the control group. (4) Conclusions: These differentially expressed proteins identified in CRSwNP are involved in airway inflammatory reaction, immune response, and oxidative stress. In particular, the identification of increased interleukin-36 gamma (IL-36γ), which contributes to inflammatory response, and a decrease in SOD, in this group are notable findings. In the future, several of these proteins may prove useful for exploring the pathogenesis of nasal polyps and chronic sinusitis or as objective biomarkers for quantitatively monitoring disease progression or response to therapy.

Antimicrobial resistance is a major health hazard worldwide. Combining azithromycin (AZ) and ciprofloxacin (CIP) in one drug delivery system was proposed to boost their antibacterial activity and overcome resistance. This study aims to improve azithromycin and ciprofloxacin activity by co-encapsulating them inside chitosan-coated polymeric nanoparticles and evaluating their antibacterial activity. The double emulsion method was employed to co-encapsulate AZ/CIP inside chitosan-coated polymeric nanoparticles. The formulations were evaluated for their nanoparticle size, size distribution, and zeta potential. Differential scanning calorimetry (DSC) analysis characterized the formula's thermal sustainability. Encapsulation efficiency was measured by HPLC and spectrophotometric analysis. Morphological studies used the Transmission Electron Microscopy (TEM). The in vitro release profiles of both AZ and CIP were monitored utilizing the dialysis membrane bag method. The micro-dilution assay assessed the antimicrobial activity against a clinical isolate of . The prepared AZ/CIP-poly-caprolactone nanoparticles were spherical; their size range was 184.0 ± 3.3-190.4 ± 5.6 nm and had high size uniformity (poly-dispersity index below 0.2). The zeta potential ranged from -21.2 ± 2.4 to -27.0 ± 2.5 mV, while chitosan-coated nanoparticles showed a positive zeta potential value ranging from 8 to 11 mV. The thermal study confirmed the amorphous state of both antibiotics inside the nanoparticles. The results of the in vitro release study indicated a slow and uniform rate of release for both drugs extended over 4-days, with a faster rate in the case of AZ. The MIC values reported for both chitosan-coated NP have been tremendously reduced by at least 15 folds of pure CIP and more than 60 folds of pure AZ. The co-encapsulation of AZ/CIP into chitosan-coated polymeric nanoparticles has been successfully achieved. The produced particles showed many beneficial attributes of uniform particle sizes below 200 nm and high zeta potential values. Chitosan-coated polymeric nanoparticles extensively enhanced the antibacterial activity of both AZ/CIP against bacteria.

Background: The emergence of multidrug-resistant bacteria presents a significant global health threat. Liposomal antibiotics have shown a potential to improve antibiotic delivery and efficacy. This study aimed to develop liposomes encapsulating tobramycin (TOB) and methylglyoxal (MGO) to enhance TOB activity while reducing bacterial adhesion and biofilm formation. Methods: Clinical isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae were characterized using whole-genome sequencing. Liposomes (Lip-MGO-TOB) were formulated using Manuka honey as a surfactant and loaded with MGO and TOB. Antibacterial activity, biofilm formation, and bacterial cell adhesion assays were performed to compare the efficacy of Lip-MGO-TOB against free TOB. Liposome characterization included analyses of morphology, zeta potential, TOB encapsulation efficiency, and stability under various biological conditions. Results: The Lip-MGO-TOB formulation, at a minimum inhibitory concentration (MIC) of 32 µg/mL, reduced the biofilm formation of the P. aeruginosa isolate (PA85) by 68%. Conversely, free TOB, at a MIC of 64 µg/mL, achieved only a 21% reduction. For the K. pneumoniae isolate (KP57), Lip-MGO-TOB inhibited bacterial adhesion to A549 cells at a lower concentration (256 µg/mL) compared to free TOB (512 µg/mL). Lip-MGO-TOB demonstrated sustained drug release over 24 h under tested conditions and retained over 99% of TOB. Conclusions: The Lip-MGO-TOB formulation significantly enhanced TOB activity against resistant bacteria compared to free TOB. Additionally, it provided a stable drug delivery system with controlled drug release. Liposomal TOB represents a promising advancement in combating antibiotic resistance by improving the efficacy and delivery of conventional antibiotics.