Abstract |
The current treatments used in inflammatory bowel disease (IBD) therapy have significant side effects. Thus, it is very necessary to position and release TNF-α siRNA in inflamed tissues. Here, we demonstrate that poly(lactic-co-glycolic acid) can pack TNF-α siRNA efficiently into nanoparticles (NPs), and galactosylated chitosan (GC) can be grafted onto the NP surface, improving the RAW 264.7 macrophage-targeting kinetics of the NPs in vitro. Next, we orally administered GC-modified NPs loaded with TNF-α siRNA to C57BL/6 mice treated with 3% dextran sodium sulfate (DSS) to investigate their use in the treatment of colitis. When TNF-α siRNA loaded NPs were released into the colitis tissues of mice, GC-modified NPs (GPNs) alleviated the inflammation more efficiently than unmodified PGLA NPs (PNs). A series of colitis parameters (e.g., weight loss, myeloperoxidase (MPO) activity) demonstrated that GPNs have better anti-inflammatory effects than PNs. As indicated by flow cytometry, grafting GC onto NPs increased the macrophage uptake capacity and improved the kinetics of endocytosis. Collectively, our findings indicate that GC- modified TNF-α siRNA loaded NPs are powerful and efficient nanoscale materials for the delivery of therapeutic molecules to colitis tissues.
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Authors | Yuzhe Huang, Jian Guo, Shuangying Gui |
Journal | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
(Eur J Pharm Sci)
Vol. 125
Pg. 232-243
(Dec 01 2018)
ISSN: 1879-0720 [Electronic] Netherlands |
PMID | 30315858
(Publication Type: Journal Article)
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Copyright | Copyright © 2018. Published by Elsevier B.V. |
Chemical References |
- RNA, Small Interfering
- Tumor Necrosis Factor-alpha
- Polylactic Acid-Polyglycolic Acid Copolymer
- Chitosan
- Galactose
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Topics |
- Animals
- Chitosan
(administration & dosage, chemistry)
- Colitis, Ulcerative
(therapy)
- Galactose
(administration & dosage, chemistry)
- Male
- Mice
- Mice, Inbred C57BL
- Nanoparticles
(administration & dosage)
- Polylactic Acid-Polyglycolic Acid Copolymer
(administration & dosage)
- RAW 264.7 Cells
- RNA, Small Interfering
(administration & dosage)
- Tumor Necrosis Factor-alpha
(genetics)
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