Journal
MOLECULAR PHARMACEUTICS
Volume 11, Issue 7, Pages 2051-2061Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp400723j
Keywords
inflammatory bowel disease; nanoparticle; drug delivery; artificial model
Funding
- National Science Fund for Distinguished Young Scholars [81025019]
- National Basic Research Program of China [2012CB517603]
- Program for New Century Excellent Talents in University [NCET-13-0272]
- National Natural Science Foundation of China [J1103512, J1210026, 31070722, 31271013, 31071232, 31170751, 31200695, 51173076, 91129712, 81102489]
- Chinese Ministry of Education [108059]
- Ph.D. Programs Foundation of the Ministry of Education of China [20100091120020, 20130091110037]
- Jiangsu Planned Projects for Postdoctoral Research Funds [1302009B]
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Functional engineered nanoparticles are promising drug delivery carriers. As the construction of a functional nanocarrier always needs the optimization of multiple technical variables, efficient in vitro high-throughput evaluation methods would help to shorten the development cycle. In the present study, we generated a tissue mimic of the colon of inflammatory bowel disease (IBD) patients. Generally, Caco-2 cells and THP-1 cells were grown in a 3-D matrix with different number, spatial distribution and specific extracellular cell matrix (ECM) composition according to real healthy and inflamed animal colon tissues. After interlerukin-1 beta/lipopolysaccharide (LPS) stimulation, the artificial model closely resembled the pathological features of IBD patient's colon, including massive cytokines and mucus production, epithelium defect and leukocytic infiltration. The tissue and cellular uptake of three different nanoparticles in the artificial model was similar to that in 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitic mice. Most importantly, our artificial tissue can be placed into 96-well plates for high-throughput screening of drug delivery carriers for the treatment of IBD. Our study suggested a readily achievable way to improve current methodologies for the development of colon targeted drug delivery systems.
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