article · Microorganisms
This research evaluates the encapsulation of celecoxib into cubosomal nanoparticles to combat systemic bacterial infection caused by Gram-positive bacteria. Physical characterisation showed that the formulated cubosomes formed stable, non-aggregated spherical nanoparticles with an average size of approximately 128 nanometres, a low polydispersity index, a negative surface charge, and an entrapment efficiency of 88.57 percent. In a systemic mouse infection model, oral administration of the celecoxib-loaded cubosomes significantly reduced bacterial loads in the liver and spleen. The treatment also diminished organ inflammation, evidenced by histological staining and marked decreases in key inflammatory and apoptotic markers, including nuclear factor kappa B, caspase-3, interleukin-1 beta, interleukin-6, cyclooxygenase-2, and tumour necrosis factor-alpha. The findings indicate that cubosomal delivery enhances the in vivo antibacterial efficacy of celecoxib by improving its oral bioavailability.
Gram-positive bacterial pathogens rapidly develop resistance to conventional antibiotics, creating a need for new therapeutic formulations. By repurposing the anti-inflammatory drug celecoxib within lipid cubosomes, this approach demonstrates how nanoscale delivery systems can penetrate bacterial layers and boost drug absorption. This provides a potential strategy to simultaneously lower bacterial counts and alleviate harmful organ inflammation during severe systemic infections.
This work demonstrates an early-stage therapeutic delivery concept tested in animal models. The technology could interest pharmaceutical developers seeking nanocarrier formulations to repurpose existing therapeutics against resistant bacterial infections. Because testing remains at the pre-clinical in vivo stage in mice, substantial further development, toxicology, and clinical testing are required before the formulation can be considered for real-world medical use.
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are ubiquitous Gram-positive pathogenic bacteria and are rapidly acquiring antibiotic resistance. Here, celecoxib was encapsulated into cubosomal nanoparticles, and the particle morphology, size distribution, zeta potential, entrapment efficiency, and celecoxib release were evaluated in vitro. Also, a systemic infection model in mice elucidated the in vivo antibacterial action of the celecoxib cubosomes. Cubosomes are a nanotechnology-based delivery system which can adhere to the external peptidoglycan layers of Gram-positive bacteria and penetrate them. The size distribution investigation revealed that the prepared celecoxib-loaded cubosomes had a mean particle size of 128.15 ± 3.04 nm with a low polydispersity index of 0.235 ± 0.023. The zeta potential measurement showed that the prepared cubosomes had a negative surface charge of -17.50 ± 0.45, indicating a highly stable nanodispersion formation with little susceptibility to particle aggregation. The cubosomal dispersion exhibited an entrapment efficiency of 88.57 ± 2.36%. The transmission electron micrograph for the prepared celecoxib-loaded cubosomes showed a narrow size distribution for the cubosomal nanoparticles, which had a spherical shape and were non-aggregated. The tested cubosomes diminished the inflammation in the treated mice's liver and spleen tissues, as revealed by hematoxylin and eosin stain and Masson's trichrome stain. The immunostained tissues with nuclear factor kappa B and caspase-3 monoclonal antibodies revealed a marked decrease in these markers in the celecoxib-treated group, as it resulted in negative or weak immunostaining in liver and spleen that ranged from 4.54% to 17.43%. This indicates their inhibitory effect on the inflammatory pathway and apoptosis, respectively. Furthermore, they reduced the bacterial burden in the studied tissues. This is alongside a decrease in the inflammatory markers (interleukin-1 beta, interleukin-6, cyclooxygenase-2, and tumor necrosis factor-alpha) determined by ELISA and qRT-PCR. The IL-1β levels were 16.66 ± 0.5 pg/mg and 17 ± 0.9 pg/mg in liver and spleen, respectively. Also, IL-6 levels were 85 ± 3.2 pg/mg and 84 ± 2.4 pg/mg in liver and spleen, respectively. In conclusion, the current study introduced cubosomes as an approach for the formulation of celecoxib to enhance its in vivo antibacterial action by improving its oral bioavailability.
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DOI: 10.3390/microorganisms11092247
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