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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-PPN...

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Published in:Chinese chemical letters 2022-10, Vol.33 (10), p.4617-4622
Main Authors: Cui, Yaxin, Zhu, Tianyu, Zhang, Xueyan, Chen, Jicong, Sun, Fengying, Li, Youxin, Teng, Lesheng
Format: Article
Language:English
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Summary: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 µg/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. We report a membrane-penetrating peptide and PEG-modified lipid polymer hybrid nanoparticles that can orally deliver superoxide dismutase (SOD) for the treatment of ulcerative colitis. [Display omitted] .
ISSN:1001-8417
1878-5964
DOI:10.1016/j.cclet.2022.03.077