Oral Administration of PLGA Nanoparticles to Deliver Antisense Oligonucleotides to Inflammatory Lesions in the Gastrointestinal Tract
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- Yagi Yuta
- Research Center, Mochida Pharmaceutical Co., Ltd. Graduate School of Systems Life Sciences, Kyushu University
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- Liu Yiwei
- Department of Applied Chemistry, Faculty of Engineering, Kyushu University
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- Li Jinting
- Graduate School of Systems Life Sciences, Kyushu University
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- Shimada Shunsuke
- Research Center, Mochida Pharmaceutical Co., Ltd.
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- Ohkouchi Munetaka
- Research Center, Mochida Pharmaceutical Co., Ltd.
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- Taguchi Yasushi
- Research Center, Mochida Pharmaceutical Co., Ltd.
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- Nii Teruki
- Department of Applied Chemistry, Faculty of Engineering, Kyushu University
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- Mori Takeshi
- Department of Applied Chemistry, Faculty of Engineering, Kyushu University Center for Future Chemistry, Kyushu University
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- Katayama Yoshiki
- Department of Applied Chemistry, Faculty of Engineering, Kyushu University Center for Future Chemistry, Kyushu University Center for Molecular Systems, Kyushu University Center for Advanced Medical Open Innovation, Kyushu University Department of Biomedical Engineering, Chung Yuan Christian University
抄録
<p>In this study, we prepared antisense oligonucleotide (ASO)-encapsulated nanoparticles (NPs) with a suitable profile for oral administration for the treatment of inflammatory bowel disease (IBD). We chose a water-in-oil-in-water (w/o/w) method to prepare the NPs using poly(lactide-co-glycolide) as a matrix and Pluronic as a stabilizer. The obtained NPs had a suitable diameter (158 nm) for the penetration of the mucus layer, endocytic uptake by enterocytes, and accumulation in inflammatory lesions in the intestine. The amount of ASOs in the NPs was relatively large (6.41% (w/w)). When the NPs were stably dispersed in solutions that mimicked gastrointestinal (GI) juice, minimal leakage of ASOs was demonstrated over the required period. The NPs were administered orally to mice with colitis induced by dextran sodium sulfate, which reduced target gene expression in the colons and rectums of the mice, whereas naked ASO administration caused no reduction in gene expression. Thus, the NPs have the potential of promising oral carriers of ASOs for the treatment of IBD that specifically target inflammatory lesions in the GI tract, thereby reducing the non-specific toxic effects of ASOs.</p>
収録刊行物
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- Ｂｉｏｌｏｇｉｃａｌ ＆ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｂｕｌｌｅｔｉｎ
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Ｂｉｏｌｏｇｉｃａｌ ＆ Ｐｈａｒｍａｃｅｕｔｉｃａｌ Ｂｕｌｌｅｔｉｎ 47 (4), 848-855, 2024-04-15
公益社団法人 日本薬学会