한빛사논문
S. M. Shatil Shahriar,†,‡,∇ Jeong Man An,†,‡,§,∇ Mohammad Nazmul Hasan,∥ Sachin S. Surwase,⊥ Yeu-Chun Kim,⊥ Dong Yun Lee,#,g Sungpil Cho*h and Yong-kyu Lee*,†,‡,∥,h
†Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju-27469, Republic of Korea
‡KB Biomed Inc., Chungju 27469, Republic of Korea
§Department of Bioengineering, College of Engineering, Hanyang University, Seoul 04763, Republic of Korea
∥Department of Green BioEngineering, Korea National University of Transportation, Chungju27469, Republic of Korea
⊥Department of Chemical & Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon-34141, Republic of Korea
#Department of Bioengineering, College of Engineering, and BK21 PLUS Future Biopharmaceutical Human Resources Training and Research Team, Hanyang University, Seoul 04763, Republic of Korea
gInstitute of Nano Science and Technology (INST), Hanyang University, Seoul 04763, Republic of Korea
h4D Biomaterials Center, Korea National University of Transportation, Jeungpyeong 27909, Republic of Korea
∇These authors contributed equally.
*Corresponding author.
Abstract
Herein, a bile acid-inspired triple padlock oral gene delivery platform is developed, facilitating the protection of the therapeutic gene from gastrointestinal degradation, selective intestinal accumulation through a bile acid-specific transporter, and transportation of pDNA NPs through the enterohepatic recycling system. This nonviral oral gene delivery nanoparticle exhibits excellent gene expression kinetics in in vitro, in vivo, and ex vivo studies. A single oral dose leads to maintaining normoglycemia for up to 7 days in three different diabetes mouse models and 14 days in diabetic monkeys. Also, the optimized dosage form can reduce nonfast blood glucose levels and hemoglobin A1C within a normal range from the last stage diabetes conditions with a reduction of weight gain from changes of food uptake behavior after treatment once weekly for 20 weeks. Taken together, the current findings could improve the current painful treatment experience of diabetics and thus improve their quality of life.
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