Exploitation of a rod-shaped, acid-labile curcumin-loaded polymeric nanogel system in the treatment of systemic inflammation

doi:10.1016/j.msec.2021.112597

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Title:	Exploitation of a rod-shaped, acid-labile curcumin-loaded polymeric nanogel system in the treatment of systemic inflammation
Authors:	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
Contributors:	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
Keywords:	cellular internalization response syndrome delivery nanoparticles pyridoxal biodistribution endocytosis doxorubicin stability mediators
Date:	2022
Issue Date:	2023-12-11 13:57:05 (UTC+8)
Publisher:	ELSEVIER
Abstract:	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.
Relation:	Biomaterials Advances, v.133, Article 112597
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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