Calcium ion coordinated dexamethasone supramolecular hydrogel as therapeutic alternative for control of non-infectious uveitis

Publication date: Available online 10 May 2017
Source:Acta Biomaterialia
Author(s): Wei Wu, Zhaoliang Zhang, Taotao Xiong, Wenguang Zhao, Rou Jiang, Hao Chen, Xingyi Li
Supramolecular hydrogel formed by the self-assembly of therapeutic agents have received considerable attention due to its high drug payload, carrier-free features. Herein, we constructed a dexamethasone sodium phosphate (Dex) supramolecular hydrogel in combination of Dex and calcium ion (Ca²⁺) and further demonstrated its therapeutic efficacy in the control of ocular inflammation. The developed supramolecular hydrogel was thoroughly characterized by rheology, TEM, FTIR and XRD. Calcium ions and Dex concentration had markedly influence on the sol-gel transition behavior of hydrogel and the proposed Dex supramolecular hydrogel displayed thixotropic property. Drug release rate from Dex supramolecular hydrogel was dependent on the Ca²⁺ concentration. In comparison with Dex aqueous solution, single intravitreal injection of Dex supramolecular hydrogel up to 30μg/eye were well ocular tolerated without causing undesirable complications of fundus blood vessel tortuosity and lens opacity, as indicated by electroretinograms (ERGs), fundus photography and histopathology. Moreover, medication by Dex supramolecular hydrogel exhibited a comparable anti-inflammatory efficacy with native Dex solution on an experimental autoimmune uveitis (EAU) model induced in Lewis rat with IRBP peptide and the therapeutic efficacy had a dosage-dependent manner. Histological observation and cytokines measurements indicated that both Dex solution and Dex supramolecular hydrogel (30μg/eye) treatment could significantly attenuate the inflammatory response in both anterior and posterior chamber via the downregulation of Th1 and Th17 effector response. All these data suggested that the developed Dex supramolecular hydrogel might be a therapeutic alternative for non-infectious uveitis with the minimal risk of the induction of lens opacity and fundus blood vessel tortuosity.Statement of significanceA facile ionic cross-linking strategy were exploited to construct a dexamethasone sodium phosphate (Dex) supramolecular hydrogel composed of Dex and calcium ion. Intravitreal injection of Dex hydrogel displayed excellent intraocular biocompatibility without causing the complications of fundus blood vessel tortuosity and cataract formation. More importantly, the proposed Dex hydrogel exhibited a comparative anti-inflammatory response with native Dex formulation in experimental autoimmune uveitis (EAU) model via the downregulation of Th1 and Th17 effector response.

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