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An In Situ Depot for Continuous Evolution of Gaseous H(2) Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis #MMPMID29923670
Wan WL; Lin YJ; Shih PC; Bow YR; Cui Q; Chang Y; Chia WT; Sung HW
Angew Chem Int Ed Engl 2018[Jul]; 57 (31): 9875-9879 PMID29923670show ga
Inflammation is involved in many human pathologies, including osteoarthritis (OA). Hydrogen (H(2) ) is known to have anti-inflammatory effects; however, the bioavailability of directly administered H(2) gas is typically poor. Herein, a local delivery system that can provide a high therapeutic concentration of gaseous H(2) at inflamed tissues is proposed. The delivery system comprises poly(lactic-co-glycolic acid) microparticles that contain magnesium powder (Mg@PLGA MPs). Mg@PLGA MPs that are intra-muscularly injected close to the OA knee in a mouse model can act as an in situ depot that can evolve gaseous H(2) continuously, mediated by the cycle of passivation/activation of Mg in body fluids, at a concentration that exceeds its therapeutic threshold. The analytical data that are obtained in the biochemical and histological studies indicate that the proposed Mg@PLGA MPs can effectively mitigate tissue inflammation and prevent cartilage from destruction, arresting the progression of OA changes.