Intra-Articular injection of acid-sensitive stearoxyl-ketal-dexamethasone microcrystals for long-acting arthritis therapy

Yang Xu; Ziqi Chen; Zunkai Xu; Yanyan Du; Jianghao Han; Xiaoyong Yuan; Shubiao Zhang; Shutao Guo

doi:10.1016/j.ajps.2020.07.002

Intra-Articular injection of acid-sensitive stearoxyl-ketal-dexamethasone microcrystals for long-acting arthritis therapy

Asian J Pharm Sci. 2021 Mar;16(2):213-221. doi: 10.1016/j.ajps.2020.07.002. Epub 2020 Jul 30.

Authors

Yang Xu¹, Ziqi Chen¹, Zunkai Xu¹, Yanyan Du², Jianghao Han¹, Xiaoyong Yuan³, Shubiao Zhang², Shutao Guo¹

Affiliations

¹ Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
² Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, Dalian Minzu University, Dalian 116600, China.
³ Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin 300022, China.

Abstract

Despite advances in treatment of chronic arthritis, there is still a strong need for the development of long-acting formulations that can enable local and sustained drug release at the inflamed tissues. In this work, we fabricated microcrystals of an acid-sensitive stearoxyl-ketal-dexamethasone prodrug for treatment of arthritis. Microcrystals of the prodrug with two sizes were successfully engineered and showed pH-dependent hydrolysis kinetics in vitro. In a collagen-induced arthritis rat model, we evaluated the influence of particle size and injection dose on anti-inflammatory effect after intra-articular injection. Such prodrug demonstrated long-acting anti-arthritis effects with good safety. Our results indicate ketal-based prodrugs are promising for the development of long-acting injectables and may stimulate the development of new treatments for chronic diseases.

Keywords: Arthritis; Dexamethasone; Long-acting formulations; Microcrystals; Prodrugs.