RESEARCH ARTICLE–Pharmaceutics, Drug Delivery and Pharmaceutical Technology
Targeted Delivery of NK007 to Macrophages to Treat Colitis

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ABSTRACT

Macrophages are important therapeutic targets for various disorders, including infectious diseases, inflammatory diseases, metabolic diseases, and cancer. In this study, we report a novel oral delivery system for the targeted delivery of anti-inflammatory therapeutics to macrophages. Using this formulation, the model drug tylophorine malate (NK007) was tightly incorporated inside beta-glucan particle shells by the formation of colloidal particles with chitosan, tripolyphosphate, and alginate via electrostatic interactions. This formulation specifically delivered NK007 to macrophages in vivo after oral gavage and effectively cured colitis in the dextran sulfate sodium-induced murine colitis model, highlighting the utility of beta-glucan particles as an oral anti-inflammation drug delivery system by targeting macrophages. In this work, NK007 was selected as the model drug. However, this novel oral carrier system has the potential to be applied as a platform for the treatment of many other diseases for which macrophages are the therapeutic targets.

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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  • Cited by (0)

    Siming Chen and Jin Wang contributed equally to this work.

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