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.

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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