Modular Acid-Activatable Acetone-Based Ketal-Linked Nanomedicine by Dexamethasone Prodrugs for Enhanced Anti-Rheumatoid Arthritis with Low Side Effects.
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| Abstract |
Given the physically encapsulated payloads with drug burst release and/or low drug loading, it is critical to initiate an innovative prodrug strategy to optimize the design of modular nanomedicines. Here, we designed modular pH-sensitive acetone-based ketal-linked prodrugs of dexamethasone (AKP-dexs) and formulated them as nanoparticles. We comprehensively studied the relationships between AKP-dex structure and properties, and we selected two types of AKP-dex-loaded nanoparticles for in vivo studies on the basis of their size, drug loading, and colloidal stability. In a collagen-induced arthritis rat model, these AKP-dex-loaded nanoparticles showed higher accumulation in inflamed joints and better therapeutic efficacy than free dexamethasone phosphate with less-severe side effects. AKP-dex-loaded nanoparticles may be useful for treating other inflammatory diseases and thus have great translational potential. Our findings represent an important step toward the development of practical applications for acetone-based ketal-linked prodrugs and are useful in the design of modular nanomedicines.
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| Authors | Yang Xu, Jingqing Mu, Zunkai Xu, Haiping Zhong, Ziqi Chen, Qiankun Ni, Xing-Jie Liang, Shutao Guo |
| Journal | Nano letters (Nano Lett) Vol. 20 Issue 4 Pg. 2558-2568 (04 08 2020) ISSN: 1530-6992 [Electronic] United States |
| PMID | 32167768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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