Tag Archives: animal model

Nifuroxazide-loaded cubosomes for pulmonary delivery attenuates bleomycin-induced lung fibrosis

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By Sameh Saber, Mohamed Nasr, Simona Cavalu & al

This study highlights the importance of cubosomes as a drug delivery
system in enhancing the bioavailability of nifuroxazide (NXZD), a poorly soluble STAT3 inhibitor. NXZD loaded cubosomes (NXZD-LC) were in vitro and in vivo evaluated. In vitro, cubosomes presented a poly-angular
nanosized particles with a mean size and zeta potential of 223.73 ± 4.73 nm and 20.93 ± 2.38 mV, respectively. The entrapment efficiency of nifuroxazide was 90.56 ± 4.25%. The in vivo pharmacokinetic study and the
lung tissue accumulation of NXZD were performed by liquid chromatography-tandem mass spectrometry after oral administration to rats. The nanoparticles exhibited a two-fold increase and 1.33 times of bioavailability and lung tissue concentration of NXZD compared to NXZD dispersion, respectively. In view of this, NXZD-LC effectively
attenuated PF by targeting STAT3 and NF-κB signals. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.

NXZD-loaded cubosomes; Mean plasma concentration-time profile (mean ± SD) after intra-gastric administration of NXZD suspension and
NXZD-loaded cubosomes. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.
Effect of NXZD suspension and NXZD-loaded cubosomes on lung tissue histological features in intratracheal bleomycin-exposed rats. BLMC group exhibited a massive
inflammatory-cell infiltration (arrows), alveolar wall thickening (arrowhead), and the highest inflammation score. BLMC + NXZD showed moderate
inflammatory-cell infiltration (arrow) and alveolar wall thickening (arrowhead) and a non-significant difference in the inflammatory score compared with that of
BLMC group.Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.
Effect of NXZD suspension and NXZD-loaded cubosomes on lung tissue fibrotic changes in intratracheal bleomycin-exposed rats: significant decrease in the A% of
fibrosis compared with that of BLMC group.Copyright Sameh Saber, Mohamed Nasr,
Simona Cavalu & al.
Effect of NXZD suspension and NXZDloaded
cubosomes on the levels of LDH (a)
and BALF total protein (b) in intratracheal
bleomycin-exposed rats. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.
Effect of NXZD suspension and NXZDloaded
cubosomes on MDA (a), NOx (b), GSH
(c) and SOD (d) in intratracheal bleomycinexposed
rats. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.
Effect of NXZD suspension and NXZD-loaded cubosomes on COL1A1 mRNA expression (a), hydroxyproline (b) and ICAM-1 (c) in lung tissue in intratracheal
bleomycin-exposed rats. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.
Effect of NXZD suspension and NXZD-loaded
cubosomes on TLR4 mRNA expression (a), TLR4 (b),
IL-6 (c), TNF-α (d) and MCP-1 (e) in lung tissue in
intratracheal bleomycin-exposed rats. Copyright Sameh Saber, Mohamed Nasr,
Simona Cavalu & al.
Effect of NXZD suspension and NXZDloaded
cubosomes on TGF-β1 mRNA expression
(a), TGF-β1 (b), PDGF-BB (c) and TIMP-1
(d) in intratracheal bleomycin-exposed rats. Copyright Sameh Saber, Mohamed Nasr,
Simona Cavalu & al.
Effect of NXZD suspension and NXZD-loaded cubosomes on NF-κB p65 DNA binding activity (a), STAT3 mRNA expression (b) and p-STAT3 (Tyr 705) (c) in
intratracheal bleomycin-exposed rats. Copyright Sameh Saber, Mohamed Nasr,
Simona Cavalu & al.

Nifuroxazide showed a potential anti-inflammatory effect, improved antioxidant defense, and suppressed fibrogenic mediators in the lung tissue. To conclude, cubosomes represent an advantageous pharmaceutical delivery system for enhancing pulmonary delivery of poorly soluble drugs. Additionally, since NXZD does induce cross-resistance to other antibacterial agents and does not adversely affect the physiological intestinal bacterial flora, repurposing NXZD as an antifibrotic agent is a promising challenge and new therapeutic approach for unmet therapeutic needs. Copyright Sameh Saber, Mohamed Nasr, Simona Cavalu & al.

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https://www.sciencedirect.com/science/article/pii/S0753332222001196

New therapeutic target in inflammation: Emerging role of dapagliflozin in overcoming lipopolysaccharide-mediated lung injury

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By E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Effect of dapagliflozin (5 and 10 mg/kg) on the histological features of LPS-induced lung injury. Lung specimens of the Control or DPGZ animals exhibited no
histological alterations of normal bronchioles (B), normal alveoli (A), normal airspaces (AS), and normal alveolar wall thickening (arrowhead). However, LPSexposed
rats exhibited massive inflammatory-cell infiltration of neutrophils, macrophages and lymphocytes (arrows), alveolar wall thickening (arrowheads),
fibrinous exudates (star) and the highest of both the inflammation score and the lung lesion distribution score. In contrast, DPGZ at both the lowest dose and
particularly the highest dose resulted in a marked improvement in lung histological features of lower degree of inflammatory-cell infiltration (arrows) and alveolar
wall thickening (arrowheads) and a significant decline in both the inflammation score and the lung lesion distribution score compared to LPS-exposed rats. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of DPGZ (5 and 10 mg/kg) on the level of (A) SOD, (B) CAT, (C) GSH, (D) NOx, and (E) MDA in rats with LPS-induced ALI. SOD: superoxide dismutase, CAT: catalase, GSH: reduced glutathione, NOx: nitric oxide, MDA: malondialdehyde, DPGZ: dapagliflozin, LPS:
lipopolysaccharides. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Effect of dapagliflozin treatment on inflammatory markers: MPO activity as well as MCP-1, IL-1β, IL-18, and TNF-α levels. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of DPGZ (5 and 10 mg/kg) on p-AMPK/t-AMPK ratio in rats with LPS-induced ALI.
p-AMPK: phosphorylated adenosine monophosphate phosphate kinase, t-AMPK: total adenosine monophosphate phosphate kinase, DPGZ: dapagliflozin, LPS: lipopolysaccharides. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of dapagliflozin treatment on NLRP3 levels, NLRP3 gene expression, and caspase-1 activity. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of dapagliflozin treatment on NF-kB P65 binding activity and NFĸB p65 (pSer536) levels in rats with LPS-induced ALI. NF-kB: nuclear factor kappa B, DPGZ: dapagliflozin, LPS: lipopolysaccharides. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Acute lung injury (ALI) is one the most common causes of morbidity and mortality in critically ill patients. In this study, we examined for first time the role of dapagliflozin (DPGZ) in lipopolysaccharide (LPS)-induced ALI in rats and determined the underlying molecular mechanisms by evaluating the effects of DPGZ on adenosine monophosphate kinase (AMPK), nuclear transcription factor kappa B, nucleotide-binding and oligomerization domain-like receptor 3 inflammasome activation. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Full text available at : https://www.sciencedirect.com/science/article/pii/S0753332222000166#fig0005