Oral delivery of superoxide dismutase by lipid polymer hybrid nanoparticles for the treatment of ulcerative colitis

Protein-based drugs have received extensive attention in the field of drug research in recent years. However, protein-based drug activity is difficult to maintain during oral delivery, which limits its application. This study developed bifunctional oral lipid polymer hybrid nanoparticles (R8-PEG-PPNPs) that deliver superoxide dismutase (SOD) for the treatment of ulcerative colitis (UC). R8-PEG-PPNPs was composed of PCADK, PLGA, lecithin, and co-modified with stearic acid-octa-arginine and polyethylene glycol. The nanoparticles (NPs) are uniformly dispersed with a complete spherical structure. In vitro stability and release studies showed that R8-PEG-PPNPs exhibited good stability and protection. In vitro cell culture experiments demonstrated that R8-PEG-PPNPs as carriers have no significant toxic effects on cells at concentration below 1000 mu g/mL and promote cellular uptake. In experiments with ulcerative colitis mice, R8-PEG- PPNPs were able to enhance drug absorption by intestinal epithelial cells and accumulate effectively at the site of inflammation. Its therapeutic effect further demonstrates that R8-PEG-PPNPs are a promising delivery system for oral delivery of protein-based drugs. (C) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

Protein-based drugs face challenges in maintaining activity during oral delivery. This study developed bifunctional oral lipid polymer hybrid nanoparticles to deliver superoxide dismutase (SOD) for ulcerative colitis (UC) treatment, showing promising results in enhancing drug absorption and therapeutic effect.