RESEARCH ARTICLE–Pharmaceutics, Drug Delivery and Pharmaceutical TechnologyTargeted Delivery of NK007 to Macrophages to Treat Colitis
Section snippets
INTRODUCTION
Macrophages play important roles in the pathophysiology of numerous disorders.1., 2., 3. In particular, macrophages form an important line of defense against bacterial and viral infection,4., 5. but have detrimental functions in chronic inflammatory diseases such as bowel disease,6 rheumatoid arthritis (RA),7 and multiple sclerosis8 as well as in metabolism diseases, atherosclerosis,9 and cancer.10., 11. Thus, macrophages are well- known therapeutic targets for various diseases.12., 13., 14.
Materials
Low guluronic content, low-viscosity sodium alginate (100–200 mPa s), and low-molecular-weight (MW) chitosan (MW 10–20 kDa) were purchased from Heowns (Tianjin, P. R. China). NK007 was synthesized according to the procedure described in our previous study.47 Prednisone was purchased from Lisheng Chemical Company (Tianjin, P. R. China). LPS (Escherichia coli serotype 0111:B4) was obtained from Sigma (St. Louis, Missouri). DSS (MW 36–50 kDa) was purchased from MP Biomedical (Solon, Ohio). Fecal
Preparation of GMP-NK007
Baker’s yeast provides a hard shell containing a glucan layer as the skeleton and a mannan shell for targeting. After removing the nucleic acids, proteins, and organelles by processing with acid, alkali, isopropanol, and acetone, the hollow and porous GMPs of the yeast shells were retained. In previous studies, we used chitosan, TPP, and sodium alginate as “fixing materials” to encapsulate protein molecules inside the hollow GMPs through anionic and cationic electrostatic interactions. Chitosan
CONCLUSIONS
In this study, we report a novel oral delivery system based on beta-glucan polymers for targeting macrophages for the treatment of inflammatory diseases. The model drug NK007 was tightly encapsulated inside GMPs, and was specifically delivered to macrophages in vivo via oral gavage. This formulation effectively cured colitis in the DSS-induced murine colitis model, highlighting the ability of beta-glucan particles to serve as an efficient oral drug delivery system targeted to macrophages with
ACKNOWLEDGMENTS
This work was supported by the Research Fund for the Doctoral Program of Higher Education of China (No. 20110031110019 and No. 20110031120018) and the National Natural Science Foundation of China (No. 31270926).
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Siming Chen and Jin Wang contributed equally to this work.