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

Xu, Y (Xu, Yang)^{[ 1,2 ]} ; Chen, ZQ (Chen, Ziqi)^{[ 1,2 ]} ; Xu, ZK (Xu, Zunkai)^{[ 1,2 ]} ; Du, YY (Du, Yanyan)^{[ 3 ]} ; Han, JH (Han, Jianghao)^{[ 1,2 ]} ; Yuan, XY (Yuan, Xiaoyong)^{[ 4 ]} ; Zhang, SBA (Zhang, Shubiao)^{[ 3 ]} ; Guo, ST (Guo, Shutao)^{[ 1,2 ]}

ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2021, 16(2): 213-221

DOI: 10.1016/j.ajps.2020.07.002

摘要

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. (c) 2020 Shenyang Pharmaceutical University. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)