한빛사논문
- 조회557
Byeongmin Park1,2, Geonhee Han1,2, Do Young Jin3, Ki Cheol Gil1,4, Dongwon Shin1,4, Jongwon Lee1,4, Jung Yeon Park4, Hochung Jang1,5, Daeho Park1, Sangmin Lee2, Kwangmeyung Kim6, Yoosoo Yang1,5, Yongju Kim4, Jun-Seob Kim3*, Sun Hwa Kim1,4*, and Man Kyu Shim1*
1Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
2College of Pharmacy, Graduate School of Pharmaceutical Sciences, Kyung Hee University, Seoul 02453, Republic of Korea
3Department of Nano-Bioengineering, Incheon National University, Incheon 22012, Republic of Korea
4KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea
5Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea
6College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
B.P. and G.H. contributed equally to this work.
*Corresponding Authors : Jun-Seob Kim, Sun Hwa Kim, Man Kyu Shim
Abstract
While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine’s pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect. This retention enables the efficient uptake by intestinal pro-inflammatory macrophages expressing high cathepsin B, triggering a burst release of the 5-ASA. This cascade fosters the polarization toward an M2 macrophage phenotype, diminishes inflammatory responses, and simultaneously facilitates the delivery of active agents to adjacent epithelial cells. Therefore, the nanoassemblies show outstanding therapeutic efficacy in inhibiting local inflammation and contribute to suppressing systemic inflammation by restoring damaged intestinal barriers. Collectively, this study highlights the promising role of the prodrug nanoassemblies in enhancing targeted drug delivery, potentially broadening the use of mesalamine in managing IBD.
논문정보
- Research article
- 2024년 06월 (BRIC 등록일 2024-06-13)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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