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| 標題: | Exploitation of a rod-shaped, acid-labile curcumin-loaded polymeric nanogel system in the treatment of systemic inflammation |
| 作者: | Lin, Hui-Chang
Chiang, Hao-Ping
Jiang, Wen-Ping
Lan, Yu-Hsuan
Huang, Guan-Jhong
Hsieh, Min-Tsang
Kuo, Sheng-Chu
Lo, Chun-Liang
Chiang, Yi-Ting |
| 貢獻者: | China Medical University Taiwan
Department of Pharmacy, Chia Nan University of Pharmacy & Science
China Medical University Taiwan
Asia University Taiwan
China Medical University Taiwan
China Medical University Hospital - Taiwan
National Yang Ming Chiao Tung University |
| 關鍵字: | cellular internalization
response syndrome
delivery
nanoparticles
pyridoxal
biodistribution
endocytosis
doxorubicin
stability
mediators |
| 日期: | 2022 |
| 上傳時間: | 2023-12-11 13:57:05 (UTC+8) |
| 出版者: | ELSEVIER |
| 摘要: | Curcumin is proven to have potent anti-inflammatory activity, but its low water solubility and rapid degradation in physiological conditions limit its clinical use, particularly in intravenous drug delivery. In this study, we fabricated rod-shaped, acid-labile nanogels, using high biosafe and biocompatible polymers, for intravenous application in systemic inflammation treatment. The constituent polymers of the nanogels were prepared via the conjugation of vitamin B6 derivatives, including pyridoxal and pyridoxamine, onto poly(glutamate) with ester bonds. The aldehyde groups of the pyridoxal and amine groups of the pyridoxamine on the polymers enable crosslinking using a Schiff base during the solvent evaporation procedure for the preparation of the rod-shaped nanogels. Our study is the first to introduce this linkage, which is generated from two vitamin B6 derivatives into a nanogel system. It is also the first to fabricate a rodshaped nanogel system via simple solvent evaporation. Under acidic conditions, such as those encountered in the endosomes and lysosomes within inflammatory macrophage cells spread in the whole body, imine bonds are cleaved and release payloads. The nanogel polymers were successfully synthesized and characterized, and the formation and disappearance of the Schiff base under neutral and acidic conditions were also confirmed using Fourier transform infrared spectroscopy. Following curcumin encapsulation, the long, rod-shaped nanogels were able to rapidly internalize into macrophage cells in static or adhere to cells under the flows, release their payloads in the acid milieus, and, thus, mitigate curcumin degradation. Consequently, curcumin-loaded, rod-shaped nanogels displayed exceptional antiinflammatory activity both in vitro and in vivo, by efficiently inhibiting pro-inflammatory mediator secretion. These results demonstrate the feasibility of our acid-labile, rod-shaped nanogels for the treatment of systemic inflammation. |
| 關聯: | Biomaterials Advances, v.133, Article 112597 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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