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Purpose Resveratrol (RSV) is a natural polyphenolic compound that has numerous biological effects. Owing to its poor bioavailability, only trace concentrations of RSV could be found at the site of action. Therefore, the present study was aimed at developing RSV-loaded nanospanlastics to improve its oral delivery and therapeutic activity. Methods RSV-loaded nanospanlastics were prepared using the thin film hydration technique. The developed formulations were characterized via vesicular size (VS), polydispersity index (PDI), zeta potential (ZP) measurements, fourier transform infrared (FT-IR) spectroscopy analysis and transmission electron microscopy (TEM). In vitro release profile was carried out using dialysis bag diffusion technique. In vivo study was carried out using lipopolysaccharide (LPS)-induced endotoxicity model in mice to evaluate the formulations activity. Results The results revealed the successful development of RSV-loaded nanospanlastics which exhibited EE% ranging from 45 to 85%, particle sizes ranging from 260.5 to 794.3 nm; negatively charged zeta potential (≤ − 20 mV) and TEM revealed their spherical shape. An in vitro release study showed biphasic pattern with sustained release of drug up to 24 h. In vivo results showed the superiority of RSV-loaded nanospanlastics over conventional niosomes in attenuating serum levels of liver and kidney functions (aspartate transaminase (AST), alanine transaminase (ALT), and creatinine) in LPS-induced endotoxic mice. Furthermore, both of them suppressed the elevated oxidative stress and inflammatory markers (malondialdehyde (MDA), nitric oxide (NO), and interleukin-1beta (IL-1β)) estimated in the liver and kidney tissues. However, the nanospanlastics showed a prevalence effect over conventional niosomes in kidney measurements and the histopathological examinations. Conclusions These findings reveal the potential of nanospanlastics in improving the oral delivery and therapeutic efficacy of RSV.

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