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Modular Acid-Activatable Acetone-Based Ketal-Linked Nanomedicine by Dexamethasone Prodrugs for Enhanced Anti-Rheumatoid Arthritis with Low Side Effects
journal contribution
posted on 2020-03-13, 16:34 authored by Yang Xu, Jingqing Mu, Zunkai Xu, Haiping Zhong, Ziqi Chen, Qiankun Ni, Xing-Jie Liang, Shutao GuoGiven
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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Keywords
Enhanced Anti-Rheumatoid Arthritiscetone-based k etal-linked p rodrugscollagen-induced arthritis rat modeldrug loadingLow Side EffectsModular Acid-Activatable Acetone-Based Ketal-Linked Nanomedicinenanomedicineacetone-based ketal-linked prodrugsless-severe side effectsdrug burst releaseAKP-dex-loaded nanoparticles
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