pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases

Though the anti-miR-301a (anti-miR) is a promising treatment strategy for inflammatory bowel disease (IBD), the degradability and the poor targeting of the intestine are a familiar issue. This study aimed to develop a multifunctional oral nanoparticle delivery system loaded with anti-miR for improvi...

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Main Authors: Junshan Wang, Min Yao, Jiafeng Zou, Wenxing Ding, Mingyue Sun, Ying Zhuge, Feng Gao
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/13/20/2797
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author Junshan Wang
Min Yao
Jiafeng Zou
Wenxing Ding
Mingyue Sun
Ying Zhuge
Feng Gao
author_facet Junshan Wang
Min Yao
Jiafeng Zou
Wenxing Ding
Mingyue Sun
Ying Zhuge
Feng Gao
author_sort Junshan Wang
collection DOAJ
description Though the anti-miR-301a (anti-miR) is a promising treatment strategy for inflammatory bowel disease (IBD), the degradability and the poor targeting of the intestine are a familiar issue. This study aimed to develop a multifunctional oral nanoparticle delivery system loaded with anti-miR for improving the targeting ability and the therapeutic efficacy. The HA-CS/ES100/PLGA nanoparticles (HCeP NPs) were prepared using poly (lactic-co-glycolic acid) copolymer (PLGA), enteric material Eudragit<sup>®</sup>S100 (ES100), chitosan (CS), and hyaluronic acid (HA). The toxicity of nanoparticles was investigated via the Cell Counting Kit-8, and the cellular uptake and inflammatory factors of nanoparticles were further studied. Moreover, we documented the colon targeting and pharmacodynamic properties of nanoparticles. The nanoparticles with uniform particle size exhibited pH-sensitive release, favorable gene protection, and storage stability. Cytology experiments showed that anti-miR@HCeP NPs improved the cellular uptake through HA and reduced pro-inflammatory factors. Administering anti-miR@HCeP NPs orally to IBD mice markedly reduced their pro-inflammatory factors levels and disease activity indices. We also confirmed that anti-miR@HCeP NPs mostly accumulated in the colon site, and effectively repaired the intestinal barrier, as well as relieved intestinal inflammation. The above nanoparticle is a candidate of the treatment for IBD due to its anti-inflammatory properties.
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spelling doaj.art-8f31d85c529f4d528a036f13956826b32023-11-19T17:36:18ZengMDPI AGNanomaterials2079-49912023-10-011320279710.3390/nano13202797pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel DiseasesJunshan Wang0Min Yao1Jiafeng Zou2Wenxing Ding3Mingyue Sun4Ying Zhuge5Feng Gao6Department of Gastroenterology, Chongming Branch of Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 202157, ChinaShanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaShanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaShanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaShanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaDepartment of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaThough the anti-miR-301a (anti-miR) is a promising treatment strategy for inflammatory bowel disease (IBD), the degradability and the poor targeting of the intestine are a familiar issue. This study aimed to develop a multifunctional oral nanoparticle delivery system loaded with anti-miR for improving the targeting ability and the therapeutic efficacy. The HA-CS/ES100/PLGA nanoparticles (HCeP NPs) were prepared using poly (lactic-co-glycolic acid) copolymer (PLGA), enteric material Eudragit<sup>®</sup>S100 (ES100), chitosan (CS), and hyaluronic acid (HA). The toxicity of nanoparticles was investigated via the Cell Counting Kit-8, and the cellular uptake and inflammatory factors of nanoparticles were further studied. Moreover, we documented the colon targeting and pharmacodynamic properties of nanoparticles. The nanoparticles with uniform particle size exhibited pH-sensitive release, favorable gene protection, and storage stability. Cytology experiments showed that anti-miR@HCeP NPs improved the cellular uptake through HA and reduced pro-inflammatory factors. Administering anti-miR@HCeP NPs orally to IBD mice markedly reduced their pro-inflammatory factors levels and disease activity indices. We also confirmed that anti-miR@HCeP NPs mostly accumulated in the colon site, and effectively repaired the intestinal barrier, as well as relieved intestinal inflammation. The above nanoparticle is a candidate of the treatment for IBD due to its anti-inflammatory properties.https://www.mdpi.com/2079-4991/13/20/2797anti-miR-301aoral nanoparticle delivery systemcolon targetingpH-responsiveinflammatory bowel disease
spellingShingle Junshan Wang
Min Yao
Jiafeng Zou
Wenxing Ding
Mingyue Sun
Ying Zhuge
Feng Gao
pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases
Nanomaterials
anti-miR-301a
oral nanoparticle delivery system
colon targeting
pH-responsive
inflammatory bowel disease
title pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases
title_full pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases
title_fullStr pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases
title_full_unstemmed pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases
title_short pH-Sensitive Nanoparticles for Colonic Delivery Anti-miR-301a in Mouse Models of Inflammatory Bowel Diseases
title_sort ph sensitive nanoparticles for colonic delivery anti mir 301a in mouse models of inflammatory bowel diseases
topic anti-miR-301a
oral nanoparticle delivery system
colon targeting
pH-responsive
inflammatory bowel disease
url https://www.mdpi.com/2079-4991/13/20/2797
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