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

Hernández, Aura Rocio; Boutonnet, Marine; Svensson, Birgitta; Butler, Eile; Lood, Rolf LU ; Blom, Kristina; Vallejo, Bibiana; Anderson, Chris; Engblom, Johan and Ruzgas, Tautgirdas, et al. (2019) In Journal of Controlled Release 306. p.121-129
Abstract

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... (More)

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.

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publication status
published
subject
keywords
Catalase, Epidermis, Hydrogen peroxide, Oxygen electrode, Skin microbiota, Skin tissue oxygenation, Stratum corneum, Topical and transdermal oxygen delivery
in
Journal of Controlled Release
volume
306
pages
9 pages
publisher
Elsevier
external identifiers
  • scopus:85066947791
ISSN
0168-3659
DOI
10.1016/j.jconrel.2019.06.001
language
English
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yes
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be060e5d-6bd3-4386-8bd2-44754de6a28b
date added to LUP
2019-07-01 14:00:26
date last changed
2019-07-16 04:13:47
@article{be060e5d-6bd3-4386-8bd2-44754de6a28b,
  abstract     = {<p>The development of formulation concepts for improved skin tissue oxygenation, including methods for measuring oxygen (O<sub>2</sub>) transport across biological barriers, are important research topics with respect to all processes that are affected by the O<sub>2</sub> 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 (H<sub>2</sub>O<sub>2</sub>) into O<sub>2</sub>. 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 O<sub>2</sub> electrode and the methodology is based on measurements of the electrical current generated by reduction of O<sub>2</sub> 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 O<sub>2</sub> by conversion from H<sub>2</sub>O<sub>2</sub> and proof-of-concept is presented for catalase-based transdermal O<sub>2</sub> delivery from topical formulations containing H<sub>2</sub>O<sub>2</sub>. In addition, we show that this concept can be further improved by topical application of external catalase on the skin surface, which enables transdermal O<sub>2</sub> delivery from 50 times lower concentrations of H<sub>2</sub>O<sub>2</sub>. These important results are promising for development of novel topical or transdermal formulations containing low and safe concentrations of H<sub>2</sub>O<sub>2</sub> for skin tissue oxygenation. Further, our results indicate that the O<sub>2</sub> production by catalase, derived from topically applied S. epidermidis (a simple model for skin microbiota) is relatively low as compared to the O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub>, based on native or topically applied catalase.</p>},
  author       = {Hernández, Aura Rocio and Boutonnet, Marine and Svensson, Birgitta and Butler, Eile and Lood, Rolf and Blom, Kristina and Vallejo, Bibiana and Anderson, Chris and Engblom, Johan and Ruzgas, Tautgirdas and Björklund, Sebastian},
  issn         = {0168-3659},
  keyword      = {Catalase,Epidermis,Hydrogen peroxide,Oxygen electrode,Skin microbiota,Skin tissue oxygenation,Stratum corneum,Topical and transdermal oxygen delivery},
  language     = {eng},
  pages        = {121--129},
  publisher    = {Elsevier},
  series       = {Journal of Controlled Release},
  title        = {New concepts for transdermal delivery of oxygen based on catalase biochemical reactions studied by oxygen electrode amperometry},
  url          = {http://dx.doi.org/10.1016/j.jconrel.2019.06.001},
  volume       = {306},
  year         = {2019},
}