Division of Orthopaedics, Department of Surgery, Faculty of Medicine and Health Sciences, Montreal General Hospital, Montreal, Quebec, H3G 1A4, Canada.
Faculty of Dentistry, McGill University, 2001 McGill College Avenue, Montreal, Quebec, H3A 1G1, Canada.
Acta Biomater. 2022 Jun;145:390-402. doi: 10.1016/j.actbio.2022.04.004. Epub 2022 Apr 8.
The ability of solid peroxides to provide sustained release of both oxygen and hydrogen peroxide makes them potentially suitable for oxygen release or antibacterial applications. Most recent reports using solid peroxides to augment oxygen levels do so by compounding solid peroxide powders in polymers to retard the aqueous decomposition. Compounds with peroxidase activity may be added to reduce hydrogen peroxide toxicity. Peroxides are rarely pure and are mixed with oxide and themselves decompose to form hydroxides in water. Therefore, even if buffering strategies are used, locally the pH at the surface of aqueously immersed peroxide particles is inevitably alkaline. Since pH affects the decomposition of peroxides and hydrogen peroxide stability, this study compared for the first-time the aqueous decomposition products of hydrogen and inorganic peroxides that are in use or have been used for medical applications of have been evaluated preclinically; calcium peroxide (CaO), magnesium peroxide (MgO), zinc peroxide (ZnO), sodium percarbonate (NaCO.1.5HO) and hydrogen peroxide (HO). Since plasma can be approximated to be carbonate buffered phosphate solution, we maintained pH using carbonate and phosphate buffers and compared results with citrate buffers. For a given peroxide compound, we identified not only a strong effect of pH but also of buffer composition on the extent to which oxygen and hydrogen peroxide formation occurred. The influence of buffer composition was not previously appreciated, thereby establishing in vitro parameters for better design of intentional release of specific decomposition species. STATEMENT OF SIGNIFICANCE: This paper compares for the first time the aqueous decomposition products oxygen and hydrogen peroxide of solid peroxy compounds of metal cations, (calcium, magnesium, sodium and zinc) across a pH range that could feasibly be found in the body, (pH 5,7, 9) either physiologically or pathologically. We find that in addition to pH, buffer composition is also a critically important factor, making translation from in vitro models challenging. Cytotoxicity was related to hydrogen peroxide release, alkalinity and in the case of zinc peroxide to the cation itself. In vitro and preclinical studies generally report release data from polymer-peroxide composites and rarely compare peroxides with one another. Together our data provide guidance for oxygen and ROS delivery from these inorganic materials.
固体过氧化物能够持续释放氧气和过氧化氢，这使得它们有可能适用于氧气释放或抗菌应用。最近使用固体过氧化物来提高氧气水平的报告是通过将固体过氧化物粉末与聚合物复合来延缓水分解来实现的。具有过氧化物酶活性的化合物可以添加到降低过氧化氢毒性。过氧化物很少是纯的，它们与氧化物混合，并在水中分解形成氢氧化物。因此，即使使用缓冲策略，过氧化物颗粒水浸表面的局部 pH 值也不可避免地是碱性的。由于 pH 值会影响过氧化物和过氧化氢的稳定性，因此本研究首次比较了用于或已用于医学应用的过氧化物和无机过氧化物的水分解产物，这些应用已经进行了临床前评估；过碳酸钠（NaCO.1.5HO）和过氧化氢（HO）。由于等离子体可以近似为碳酸盐缓冲磷酸盐溶液，我们使用碳酸盐和磷酸盐缓冲液来维持 pH 值，并将结果与柠檬酸盐缓冲液进行比较。对于给定的过氧化物化合物，我们不仅确定了 pH 值的强烈影响，还确定了缓冲液组成对氧气和过氧化氢形成程度的影响。以前没有意识到缓冲液组成的影响，从而为更好地设计特定分解物种的有意释放建立了体外参数。
本文首次比较了在体内可能存在的 pH 值范围内（生理或病理条件下 pH 为 5、7 和 9），金属阳离子（钙、镁、钠和锌）过氧化合物的水分解产物氧气和过氧化氢，除了 pH 值外，缓冲液组成也是一个至关重要的因素，使得从体外模型转化具有挑战性。细胞毒性与过氧化氢的释放、碱性以及在锌过氧化物的情况下与阳离子本身有关。在体外和临床前研究中，通常报告聚合物-过氧化物复合材料的释放数据，很少相互比较过氧化物。我们的数据共同为这些无机材料的氧气和 ROS 输送提供了指导。
