Elsevier

Chinese Chemical Letters

Volume 33, Issue 10, October 2022, Pages 4617-4622
Chinese Chemical Letters

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

https://doi.org/10.1016/j.cclet.2022.03.077Get rights and content

Abstract

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.

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Declaration of competing interest

The authors declare no conflict of interest.

Acknowledgments

The authors acknowledge the financial support received form National Natural Science Foundation of China (No. 82073784), Jilin Province Science and Technology Development Program (No. 20200801012GH) and Industrial Technology Research and Development Projects from the Development and Reform Commission of Jilin Province (No. 2019C050-4). Meanwhile, the authors also acknowledge Key Laboratory of Pathobiology, Ministry of Education, Jilin University.

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