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Theranostics 2023; 13(12):4030-4041. doi:10.7150/thno.85627 This issue Cite

Research Paper

Weak acid-initiated slow release of Dexamethasone from hydrogel to treat orbital inflammation

Jinjing Li¹, Aichi Zhang², Andi Zhao¹, Zhaoxia Chen³, Gaolin Liang^3✉, Hu Liu^1✉, Chengfan Wu^2✉

1. Department of Ophthalmology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
2. College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
3. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.

✉ Corresponding authors: Chengfan Wu, Doctor, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China. E-mail: wucf0220edu.cn. Hu Liu, Ph.D., Professor, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu 210029, China. E-mail: liuhuedu.cn. Gaolin Liang, Ph.D., Professor, State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China. Tel: (+86)-25-83790632; fax: (+86)-25-83790632. E-mail: gliangedu.cn. More

Abstract

Rationale: Orbital inflammation is a prevalent and prolonged ocular disease that poses a significant challenge to clinicians. Glucocorticoid Dexamethasone sodium phosphate (Dex) has demonstrated efficacy in the clinical treatment of nonspecific orbital inflammation. However, frequent administration is required due to the short half-life of Dex, which may lead to drug waste and adverse side effects.

Methods: In this study, we co-assembled Dex with a weak acid responsive hydrogelator Py-Phe-Phe-Lys-Lys-OH (K) to obtain a novel supramolecular hydrogel Dex/K that could release Dex in a slow manner to treat orbital inflammation. The therapeutic effect of Gel Dex/K on orbital inflammation was verified by in vitro and in vivo experiments.

Results: In vitro experiments indicated that co-assembly of Dex with K significantly increased mechanic strength of the hydrogel, enabling a continuous release of 40% of total Dex within 7 days. In vivo experiments further demonstrated that sustained release of Dex from Gel Dex/K could effectively alleviate the infiltration of inflammatory cells and the release of inflammatory factors in the orbit of mice, improving symptoms such as increased intraocular pressure and proptosis. Additionally, Gel Dex/K mitigated the degree of tissue fibrosis and fatty infiltration by reducing the development of local inflammation in the orbit.

Conclusions: Our research results indicate that Gel Dex/K could more efficiently achieve responsive drug release in orbit, providing an innovative method for treating orbital inflammation.

Keywords: Orbital inflammation therapy, Supramolecular hydrogel, Sustained release, Dexamethasone

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