A 3-D artificial colon tissue mimic for the evaluation of nanoparticle-based drug delivery system.
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-1β/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.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, ‡State Key Laboratory of Analytical Chemistry for Life Science, and §Jiangsu Provincial Laboratory for Nano-Technology, Nanjing University , Nanjing 210093, China.
Zhen
Z
Huang
Zhenzhen
Z
Wang
Shanshan
S
Long
Haoyang
H
Jiang
Jiangning
J
Chen
Junfeng
J
Zhang
Lei
L
Dong
D000818:Animals; D032701:Biomimetics / Q000379:methods; D018938:Caco-2 Cells; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004341:Drug Evaluation / Q000379:methods; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage*; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
D016207:Cytokines; D014302:Trinitrobenzenesulfonic Acid