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Drug delivery through the skin barrier is a topic of high interest in cosmetology and dermatology. The disruption of the skin barrier is a common method to stimulate skin penetration. In the present chapter tissue tolerable plasma is used to damage the skin barrier, enabling topically applied substances to effectively pass the stratum corneum. Subsequently to plasma-tissue interaction the skin barrier recovers immediately. Topically applied drugs have to be applied before the plasma treatment onto the skin. In this case, the plasma chemical reaction of the drug has to be prevented by using plasma resistant nanocontainers.

Cold physical plasmas ignited a technological spark in industry, biotechnology, and medicine. Especially the field of hygiene benefited of the plasma's exceptional activity against pathogenic microorganisms. Together with plasma-based surface functionalization, these qualities are highly relevant in a variety of processes in health care, such as the decontamination or sterilization of medical devices, food, packaging materials, waste water, or indoor air. In medicine, plasma has proven to show promising antiseptic results on skin and mucosal membranes in infection-related diseases in dermatology and dentistry. This comprehensive review will discuss the current applications of cold plasma in the fields of hygiene, and will provide a promising outlook on many applications yet to come.

The results of the risk assessment of the tissue-tolerable plasma (TTP) jet kINPen med ® and first results of pilot clinical studies are presented. Producing an atmospheric pressure plasma, this plasma jet entails no risk for humans in terms of temperature increase, UV radiation or free radical formation by the plasma. The antiseptic efficacy in vitro on porcine skin and in vivo on human skin was compared to that of octenidine. TTP could significantly reduce the bacterial load in comparison to untreated skin. However, the slightly reduced antiseptic properties of TTP are attributed to the current parameter set-up and technical limitations.

Kalte Plasmen zeigen eine hohe Wirksamkeit gegen Mikroorganismen und Viren sowie gegen bakterielle und fungielle Biofilme bei gleichzeitiger Vertraglichkeit fur die Korperoberflache sowie fur unbelebte Materialien. Daruber hinaus besteht die Moglichkeit der gezielten Modifikation der Eigenschaften von Mikroorganismen. Polymere und metallische Oberflachen werden durch Plasmabehandlung in ihrer Hydrophobizitat verandert; zugleich konnen Beschichtungen aufgebracht werden. Durch inflammatorische Reize, Forderung der Angiogenese und der Proliferation von Fibroblasten, Keratinozyten und Osteoblasten werden Heilungsprozesse in Gang gesetzt.

Die Verabreichung von Medikamenten in die lebende Epidermis der Haut ist weit verbreitet in der Dermatologie. Leider erreichen tatsachlich jedoch nur geringe Mengen dieser Medikamente die lebende Epidermis. Daher ist die Entwicklung und Anwendung neuer so genannter Drug-Delivery-Methoden von sehr groser Bedeutung. Wahrend die Plasmabehandlung die Hautbarriere stort, regeneriert sich die Haut sofort bei Abbruch der Plasmabehandlung. Daher mussen die Medikamente vor der Plasmabehandlung auf die Hautoberflache aufgebracht werden, die das Risiko einer plasmachemischen Reaktion beeinflussen. Hierfur werden die Wirkstoffe in so genannte Nanocontainer eingekapselt, die gegen die Plasmabehandlung resistent sind. Sobald die Nanocontainer in das lebensfahige Gewebe eingedrungen sind, erfolgt deren Wirkstofffreigabe.

The antimicrobial treatment of wounds is still a major problem. Tissue-tolerable electrical plasma (TTP) is a new approach for topical microbial disinfection of the skin surface. The aim of the present study was to investigate the influence of TTP on a carotenoid profile in relation to skin physiology parameters (epidermal barrier function, stratum corneum (SC) hydration, surface temperature and irritation parameters). We were interested in the interaction of TTP and the antioxidative network, as well as the consequences for skin physiology parameters. These parameters are also indicative of TTP safety in vivo. For plasma application, 'Kinpen 09' was used (surface exposure 30-43°C) for 3 s. Beta-carotene and water profiles were assessed by in vivo Raman microspectroscopy (skin composition analyzer 3510). Skin physiology parameters were measured with Tewameter TM 300, Corneometer CM 825, skin thermometer and Chromameter CR 300. All parameters were assessed non-invasively on seven healthy volunteers before and after plasma application in vivo. We could show that TTP application leads to a decrease in beta-carotene especially in the superficial SC. Skin-surface temperature increased by 1.74°C, while the transepidermal water loss (TEWL) increase indicated an impaired barrier function. SC hydration decreased as seen in water profile especially in the superficial layers and capacitance values. A slight increase in skin redness was measurable. The induction of reactive oxygen species is probably the major contributor of TTP efficacy in skin disinfection. Skin physiology parameters were influenced without damaging the skin or skin functions, indicating the safety of TTP under in vivo conditions.

A high number of treatments in dermatology are based on the penetration of topically applied drugs through the skin barrier. This process is predominantly inefficient, on account of the strong protection properties of the upper skin layer – the stratum corneum. If the skin barrier is damaged, the penetration efficiency of topically applied drugs increases. Therefore, different methods have been developed to influence the barrier properties of the skin. Recently, it could be demonstrated that a cold tissue tolerable plasma (TTP) produced by a plasma-jet can strongly enhance drug delivery through the skin. These investigations were performed by using a solution of fluorescent dye as a model drug. In the present study, these investigations were carried out using fluorescent silica particles at different sizes. The aim of the study was to investigate whether or not there is a limitation in size for topically applied substances to pass through the skin barrier after plasma treatment.

The application of tissue-tolerable electrical plasma (TTP) is highly efficient in skin antisepsis. However, the germs are not only located on the skin surface, but also in the hair follicles, from where they re-colonize the skin surface after antisepsis, e.g. The objective of the present study was to show that plasma is able to reach the follicular reservoir for antisepsis. For this purpose, a solution containing particulate chlorophyll dye had been applied onto porcine skin samples. The fluorescent properties of the dye changed during the plasma tissue interaction. The results demonstrate that TTP penetrates deep into the hair follicles, whereupon the hairs act as a conductor for the plasma. Therefore, it can be concluded that micro-organisms of the follicular reservoir are destroyed more efficiently by the plasma than by conventional liquid antiseptics.

Wound healing disorders frequently occur due to biofilm formation on wound surfaces requiring conscientious wound hygiene. Often, the application of conventional liquid antiseptics is not sufficient and sustainable as (1) the borders and the surrounding of chronic wounds frequently consist of sclerotic skin, impeding an effectual penetration of these products, and (2) the hair follicles representing the reservoir for bacterial recolonization of skin surfaces are not affected. Recently, it has been reported that tissue-tolerable plasma (TTP), which is used at a temperature range between 35 and 45°C, likewise has disinfecting properties. In the present study, the effectivity of TTP and a standard liquid antiseptic was compared in vitro on porcine skin. The results revealed that TTP was able to reduce the bacterial load by 94%, although the application of the liquid antiseptic remained superior as it reduced the bacteria by almost 99%. For in vivo application, however, TTP offers several advantages. On the one hand, TTP enables the treatment of sclerotic skin as well, and on the other hand, a sustainable disinfection can be realized as, obviously, also the follicular reservoir is affected by TTP.

Recently, it was reported that a plasma-jet could be efficiently applied for the antisepsis of wounds. In this case, the discharge in an argon gas stream was used to produce a so-called ``cold plasma'' on the skin surface. The thermal action of the plasma on the skin was investigated in the present study by means of laser scanning microscopy (LSM) and by histological analysis. Consequently, the plasma beam was moved with a definite velocity at an optimal distance over the skin surface. The structural changes of the tissue were analyzed. It was found by LSM that a thermal damage could be detected only in the upper cell layers of the stratum corneum (SC) at moving velocities of the plasma beam, usually applied in clinical practice. Deeper parts of the SC were not damaged. The structural changes were so superficial that they could be detected only by LSM but not by analysis of the histological sections.

Most treatments in dermatology and cosmetology are based on the penetration of topically applied drugs into the skin or through the skin barrier to the target structure in the living tissue. In the case of healthy skin, scarcely 1% of the applied drugs pass the skin barrier, depending on their chemical properties. Therefore, different physical and chemical methods have been developed to stimulate the penetration process. All these methods are based on the partial destruction of the barrier. In this study, an electrical tissue-tolerable plasma (TTP) was used to increase the penetration of a topically applied model drug (fluorescent dye) through the skin barrier. Using laser scanning microscopy, the distribution of the model drug in different depths of the skin was investigated. It was found that the plasma treatment of the skin is a very efficient process to deliver topically applied substances into the living tissue. In the case of the non-plasma-treated skin, it was found that the fluorescent dye could be detected exclusively on the skin surface. If the dye was applied to the TTP-treated skin, it could be observed in high concentration also in deeper parts of the skin extending down to the stratum basale and the papillary structure.

The application of tissue tolerable plasma (TTP) is well suited for ­disinfection of living tissue. In particular, when treating chronic wounds, it has ­several advantages in comparison to the classical application of antiseptics, which do not penetrate sufficiently into the tissue or inhibit wound regeneration. The mode of action of the plasma is mainly based on synergetic effects between temperature increase and the formation of free radicals, which destroy the bacteria and fungi.

The antimicrobial treatment of wounds is still a major problem. Tissue-tolerable electrical plasma (TTP) is a new approach for topical microbial disinfection of the skin surface. The aim of the present study was to investigate the influence of TTP on a carotenoid profile in relation to skin physiology parameters (epidermal barrier function, stratum corneum (SC) hydration, surface temperature and irritation parameters). We were interested in the interaction of TTP and the antioxidative network, as well as the consequences for skin physiology parameters. These parameters are also indicative of TTP safety in vivo. For plasma application, 'Kinpen 09' was used (surface exposure 30-43°C) for 3 s. Beta-carotene and water profiles were assessed by in vivo Raman microspectroscopy (skin composition analyzer 3510). Skin physiology parameters were measured with Tewameter TM 300, Corneometer CM 825, skin thermometer and Chromameter CR 300. All parameters were assessed non-invasively on seven healthy volunteers before and after plasma application in vivo. We could show that TTP application leads to a decrease in beta-carotene especially in the superficial SC. Skin-surface temperature increased by 1.74°C, while the transepidermal water loss (TEWL) increase indicated an impaired barrier function. SC hydration decreased as seen in water profile especially in the superficial layers and capacitance values. A slight increase in skin redness was measurable. The induction of reactive oxygen species is probably the major contributor of TTP efficacy in skin disinfection. Skin physiology parameters were influenced without damaging the skin or skin functions, indicating the safety of TTP under in vivo conditions.

Most treatments in dermatology and cosmetology are based on the penetration of topically applied drugs into the skin or through the skin barrier to the target structure in the living tissue. In the case of healthy skin, scarcely 1% of the applied drugs pass the skin barrier, depending on their chemical properties. Therefore, different physical and chemical methods have been developed to stimulate the penetration process. All these methods are based on the partial destruction of the barrier. In this study, an electrical tissue-tolerable plasma (TTP) was used to increase the penetration of a topically applied model drug (fluorescent dye) through the skin barrier. Using laser scanning microscopy, the distribution of the model drug in different depths of the skin was investigated. It was found that the plasma treatment of the skin is a very efficient process to deliver topically applied substances into the living tissue. In the case of the non-plasma-treated skin, it was found that the fluorescent dye could be detected exclusively on the skin surface. If the dye was applied to the TTP-treated skin, it could be observed in high concentration also in deeper parts of the skin extending down to the stratum basale and the papillary structure.

Regardless of the fact that several highly efficient antiseptics are commercially available, the antiseptic treatment of chronic wounds remains a problem. In the past, electrical plasma discharges have been frequently used in biometrical science for disinfection and sterilization of material surfaces. Plasma systems usually have a temperature of several hundred degrees. Recently, it was reported that "cold" plasma can be applied onto living tissue. In in vitro studies on cell culture, it could be demonstrated that this new plasma possesses excellent antiseptic properties. We perform a risk assessment concerning the in vivo application of a "cold" plasma jet on patients and volunteers. Two potential risk factors, UV radiation and temperature, are evaluated. We show that the UV radiation of the plasma in the used system is an order of magnitude lower than the minimal erythema dose, necessary to produce sunburn on the skin in vivo. Additionally, thermal damage of the tissue by the plasma can be excluded. The results of the risk assessment stimulate the in vivo application of the investigated plasma jet in the treatment of chronic wounds.