PMID- 25701029
OWN - NLM
STAT- MEDLINE
DCOM- 20151207
LR  - 20240109
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 48
DP  - 2015 Apr
TI  - An orally administrated nucleotide-delivery vehicle targeting colonic macrophages 
      for the treatment of inflammatory bowel disease.
PG  - 26-36
LID - S0142-9612(15)00030-7 [pii]
LID - 10.1016/j.biomaterials.2015.01.013 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathogenesis of 
      inflammatory bowel disease (IBD). Anti-TNF-alpha therapies have shown protective 
      effects against colitis, but an efficient tool for target suppression of its 
      secretion - ideally via oral administration - remains in urgent demand. In the 
      colon tissue, TNF-alpha is mainly secreted by the colonic macrophages. Here, we 
      report an orally-administrated microspheric vehicle that can target the colonic 
      macrophages and suppress the local expression of TNF-alpha for IBD treatment. This 
      vehicle is formed by cationic konjac glucomannan (cKGM), phytagel and an 
      antisense oligonucleotide against TNF-alpha. It was given to dextran sodium sulfate 
      (DSS) colitic mice via gastric perfusion. The unique swelling properties of cKGM 
      enabled the spontaneous release of cKGM& antisense nucleotide (ASO) nano-complex 
      from the phytagel scaffold into the colon lumen, where the ASO was transferred 
      into colonic macrophages via receptor-mediated phagocytosis. The treatment 
      significantly decreased the local level of TNF-alpha and alleviated the symptoms of 
      colitis in the mice. In summary, our study demonstrates a convenient, 
      orally-administrated drug delivery system that effectively targets colonic 
      macrophages for suppression of TNF-alpha expression. It may represent a promising 
      therapeutic approach in the treatment of IBD.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Huang, Zhen
AU  - Huang Z
AD  - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, 
      Nanjing University, Nanjing 210093, China.
FAU - Gan, Jingjing
AU  - Gan J
AD  - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, 
      Nanjing University, Nanjing 210093, China.
FAU - Jia, Lixin
AU  - Jia L
AD  - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, 
      Nanjing University, Nanjing 210093, China.
FAU - Guo, Guangxing
AU  - Guo G
AD  - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, 
      Nanjing University, Nanjing 210093, China.
FAU - Wang, Chunming
AU  - Wang C
AD  - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, 
      Nanjing University, Nanjing 210093, China; State Key Laboratory of Quality 
      Research in Chinese Medicine, Institute of Chinese Medical Sciences, University 
      of Macau, Macau SAR, Macau 999078, China.
FAU - Zang, Yuhui
AU  - Zang Y
AD  - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, 
      Nanjing University, Nanjing 210093, China.
FAU - Ding, Zhi
AU  - Ding Z
AD  - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, 
      Nanjing University, Nanjing 210093, China.
FAU - Chen, Jiangning
AU  - Chen J
AD  - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, 
      Nanjing University, Nanjing 210093, China.
FAU - Zhang, Junfeng
AU  - Zhang J
AD  - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, 
      Nanjing University, Nanjing 210093, China. Electronic address: 
      jfzhang@nju.edu.cn.
FAU - Dong, Lei
AU  - Dong L
AD  - State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, 
      Nanjing University, Nanjing 210093, China. Electronic address: 
      leidong@nju.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150207
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Nucleotides)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Cell Line
MH  - Colon/*drug effects/metabolism/pathology
MH  - In Vitro Techniques
MH  - Inflammatory Bowel Diseases/*drug therapy
MH  - Macrophages/*drug effects
MH  - Mice
MH  - Microscopy, Electron, Transmission
MH  - Microspheres
MH  - Nucleotides/*administration & dosage/pharmacokinetics
MH  - Spectroscopy, Fourier Transform Infrared
MH  - Tissue Distribution
MH  - Tumor Necrosis Factor-alpha/biosynthesis
OTO - NOTNLM
OT  - Antisense oligonucleotide
OT  - Colonic macrophages
OT  - Inflammatory bowel disease
OT  - TNF-alpha
OT  - Targeting delivery
EDAT- 2015/02/24 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/02/22 06:00
PHST- 2014/08/19 00:00 [received]
PHST- 2014/12/18 00:00 [revised]
PHST- 2015/01/20 00:00 [accepted]
PHST- 2015/02/22 06:00 [entrez]
PHST- 2015/02/24 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0142-9612(15)00030-7 [pii]
AID - 10.1016/j.biomaterials.2015.01.013 [doi]
PST - ppublish
SO  - Biomaterials. 2015 Apr;48:26-36. doi: 10.1016/j.biomaterials.2015.01.013. Epub 
      2015 Feb 7.