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Abstract: Inflammation is involved in many human pathologies, including osteoarthritis (OA). Hydrogen (H2) is known to have anti‐inflammatory effects; however, the bioavailability of directly administered H2 gas is typically poor. Herein, a local delivery system that can provide a high therapeutic concentration of gaseous H2 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 H2 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. [ABSTRACT FROM AUTHOR]

Leroux et al. performed a set of experiments reported in our study and claim that they failed to reproduce the thermoresponsive liposomal system containing ammonium bicarbonate (ABC) that could trigger drug release under mild heating. We disagree with their assessments and speculate that the different method used by Leroux et al. to prepare the aqueous ABC is the culprit. [ABSTRACT FROM AUTHOR]

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., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hydrogen gas can reduce cytotoxic reactive oxygen species (ROS) that are produced in inflamed tissues. Inspired by natural photosynthesis, this work proposes a multicomponent nanoreactor (NR) that comprises chlorophyll a, l-ascorbic acid, and gold nanoparticles that are encapsulated in a liposomal (Lip) system that can produce H 2 gas in situ upon photon absorption to mitigate inflammatory responses. Unlike a bulk system that contains free reacting molecules, this Lip NR system provides an optimal reaction environment, facilitating rapid activation of the photosynthesis of H 2 gas, locally providing a high therapeutic concentration thereof. The photodriven NR system reduces the degrees of overproduction of ROS and pro-inflammatory cytokines both in vitro in RAW264.7 cells and in vivo in mice with paw inflammation that is induced by lipopolysaccharide (LPS). Histological examinations of tissue sections confirm the ability of the NR system to reduce LPS-induced inflammation. Experimental results indicate that the Lip NR system that can photosynthesize H 2 gas has great potential for mitigating oxidative stress in tissue inflammation.