Optimized in vivo performance of acid-liable micelles for the treatment of rheumatoid arthritis by one single injection

Current therapeutic limitations existed in effective treatment of rheumatoid arthritis (RA) have motivated numerous researches on finding new strategies. Regarding to the non-targeted distribution and uncontrollable in vivo performance which hinder the effective treatment for RA, we designed an acid-responsive polymeric micelle formulation by attaching the dexamethasone (Dex) to the side chains of a wheat-like polyethylene glycol (PEG) derivate via a hydrazone linker. The self-assembly micelles with the diameter around 50 nm could passively migrate to inflamed sites. The presence of hydrazone linkers avoided the drug leakage in circulation and ensured the preferential release in acidic arthritic joints. Here, we evaluated how the polymer-drug micelles with different density of drug payloads influenced the release pattern, pharmacokinetics and biodistribution, as well as the most importantly, the duration of the therapeutic efficacy. Our exploration would offer the chemical and structural basis for designing and optimizing the nanocarriers for enhanced therapeutic efficacy.