New concepts for transdermal delivery of oxygen based on catalase biochemical reactions studied by oxygen electrode...

The development of formulation concepts for improved skin tissue oxygenation, including methods for measuring oxygen (O₂) transport across biological barriers, are important research topics with respect to all processes that are affected by the O₂ concentration, such as radiation therapy in oncology treatments, wound healing, and the general health status of skin. In this work we approach this topic by a novel strategy based on the antioxidative enzyme catalase, which is naturally present in the skin organ where it enables conversion of the reactive oxygen species hydrogen peroxide (H₂O₂) into O₂. We introduce various applications of the skin covered oxygen electrode (SCOE) as an in-vitro tool for studies of catalase activity and function. The SCOE is constructed by placing an excised skin membrane directly on an O₂ electrode and the methodology is based on measurements of the electrical current generated by reduction of O₂ as a function of time (i.e. chronoamperometry). The results confirm that a high amount of native catalase is present in the skin organ, even in the outermost stratum corneum (SC) barrier, and we conclude that excised pig skin (irrespective of freeze-thaw treatment) represents a valid model for ex vivo human skin for studying catalase function by the SCOE setup. The activity of native catalase in skin is sufficient to generate considerable amounts of O₂ by conversion from H₂O₂ and proof-of-concept is presented for catalase-based transdermal O₂ delivery from topical formulations containing H₂O₂. In addition, we show that this concept can be further improved by topical application of external catalase on the skin surface, which enables transdermal O₂ delivery from 50 times lower concentrations of H₂O₂. These important results are promising for development of novel topical or transdermal formulations containing low and safe concentrations of H₂O₂ for skin tissue oxygenation. Further, our results indicate that the O₂ production by catalase, derived from topically applied S. epidermidis (a simple model for skin microbiota) is relatively low as compared to the O₂ produced by the catalase naturally present in skin. Still, the catalase activity derived from S. epidermidis is measurable. Taken together, this work illustrates the benefits and versatility of the SCOE as an in vitro skin research tool and introduces new and promising strategies for transdermal oxygen delivery, with simultaneous detoxification of H₂O₂, based on native or topically applied catalase.