Sora Jung

Hair follicles as a target structure for nanoparticles

For at least two decades, nanoparticles have been investigated for their capability to deliver topically applied substances through the skin barrier. Based on findings that nanoparticles are highly suitable for penetrating the blood–brain barrier, their use for drug delivery through the skin has become a topic of intense research. In spite of the research efforts by academia and industry, a commercial product permitting the nanoparticle-assisted delivery of topically applied drugs has not yet been developed. However, nanoparticles of approximately 600 nm in diameter have been shown to penetrate efficiently into the hair follicles, where they can be stored for several days. The successful loading of nanoparticles with drugs and their triggered release inside the hair follicle may present an ideal method for localized drug delivery. Depending on the particle size, such a method would permit targeting specific structures in the hair follicles such as stem cells or immune cells or blood vessels found in the vicinity of the hair follicles.

Cutaneous Carotenoids: The Mirror of Lifestyle?

Carotenoids could serve as marker substances of the antioxidant status of the human skin. In the present study, an optical skin scanner was used to analyse the carotenoid concentration obtained from 4 volunteers over a period of 13 days. The measurements were taken daily at different time points. In addition, the volunteers were asked to keep track of their daily nutritional behaviour and stress situations in a diary. It was found that the carotenoid values reflect clearly the nutritional behaviour and stress situations of the volunteers. While a steady, increased intake of fruit and vegetables resulted in a gradual increase in the dermal carotenoid values for several days, stressful situations entailed an immediate decline in these values. Although the impact of healthy nutrition on the antioxidant protection system is generally known and notwithstanding the small number of cases, the present study clearly demonstrates that the avoidance and/or reduction of stress is similarly important in order not to counteract or nullify the results achieved by healthy nutrition.

Antioxidants in Asian-Korean and Caucasian Skin: The Influence of Nutrition and Stress

Background: The antioxidant status of the human skin provides protection against the destructive action of free radicals. Most antioxidants cannot be synthesized by the human organism itself, but have to be ingested with a healthy nutrition rich in fruit and vegetables. The Korean cuisine is known to be one of the healthiest worldwide. This binational study investigated the cutaneous carotenoid concentrations in German subjects, South Korean subjects and immigrant Korean subjects resident in Germany and examined whether dietary- and lifestyle-related differences are reflected in the cutaneous carotenoid concentrations. Methods: Measurements of the carotenoid concentrations of 714 healthy volunteers were performed using a non-invasive spectroscopic measurement system based on reflectance spectroscopy. Results: In the present study South Korean residents showed a significantly higher antioxidant status than both native German residents and Korean immigrants living in Germany (p < 0.001). The first generation of Korean immigrants to Germany over the age of 50 mostly preserved Korean dietary habits, showing significantly higher concentrations (p < 0.001) than the German-born second and third Korean generations under the age of 50. Conclusion: The results of the study indicate that a healthy nutrition alone does not provide a high antioxidant status unless the stress exposure can be reduced simultaneously.

Efficient Prevention Strategy against the Development of a Palmar-Plantar Erythrodysesthesia during Chemotherapy

Background: Pegylated liposomal doxorubicin (PLD) is a highly efficient chemotherapeutic; however, it induces dermal side effects such as palmar-plantar erythrodysesthesia (PPE) in up to 80% of cases, probably by being emitted with the sweat onto the skin surface. Aim: The aim of the present study was to examine whether a topically applied ointment containing antioxidants with a high radical protection factor is able to prevent the formation of PPE. Methods: Twenty patients suffering from ovarian carcinoma and treated with PLD were observed. Results: 60% of the patients tolerated the regular application of the cream and developed no PPE. The remaining 40% interrupted the application. Six of them developed PPE and resumed ointment application thereafter. In these cases the PPE disappeared or was strongly reduced. Conclusion: The results of the observation clearly demonstrate that topical application of the ointment is an efficient strategy against the development of PPE during chemotherapy with PLD.

Do nanoparticles have a future in dermal drug delivery

Abstract More and more investigations confirm that nanoparticles are incapable of overcoming the intact skin barrier in vivo. Do nanoparticles still have a future in dermal drug delivery? Unlike many other topically applied substances, nanoparticles have not been reported to utilize the intercellular penetration pathway and preferentially make use of the follicular penetration pathway. Deep penetration into the follicular ducts has been described for a variety of particles and appears to be strongly influenced by particle size. For targeted drug delivery, smart nanoparticles are required which are able to release their loaded drugs subsequent to internal or external trigger stimuli, and thereby enable the translocation of the active agents into the viable epidermis. In the recent manuscript, three nanoparticles systems are summarized and compared which release their model drugs upon different trigger mechanisms. The BSA hydrogel nanoparticles release their model drug TRITC‐dextran by passive diffusion due to a concentration gradient via a porous surface. The protease‐triggered controlled release BSA nanoparticles release their model drug if they are applied simultaneously with protease nanoparticles, resulting in an enzymatic degradation of the particles and a release of the model drug FITC. Finally, the IR‐triggered controlled release AuNP‐doped BSA nanoparticles release their model drug FITC after photoactivation with wIRA. For all three nanoparticle systems, the release of their model drugs could be observed. For the first nanoparticle system, only low follicular penetration depths were found which might by due do an agglomeration effect. For the last two nanoparticle systems, deep follicular penetration and even an uptake by the sebaceous glands were verified. In conclusion, it could be demonstrated that nanoparticles do have a future in dermal drug delivery if smart nanoparticle systems are utilized which are able to release their drug at specific times and locations within the hair follicle. Graphical abstract Figure. No Caption available. HighlightsBSA particles represent smart nanoparticle systems which can be equipped with different mechanisms for the release of the loaded drug within the hair follicle.A release of the model drug within the hair could be detected for all three nanoparticle systems, for the protease‐triggered controlled release BSA nanoparticles and the IR‐triggered controlled release AuNP‐doped BSA nanoparticles even an uptake of the model drug in the sebaceous gland could be detected.Nanoparticles can be very useful in dermal drug delivery if smart nanoparticle systems are utilized which are able to release their drug at specific times and locations within the hair follicle where the released drug can then penetrate independently in the follicle‐surrounding tissue.

Spectroscopic biofeedback on cutaneous carotenoids as part of a prevention program could be effective to raise health awareness in adolescents.

The cutaneous carotenoid concentration correlates with the overall antioxidant status of a person and can be seen as biomarker for nutrition and lifestyle. 50 high school students were spectroscopically measured for their cutaneous carotenoid concentrations initially in a static phase, followed by an intervention phase with biofeedback of their measured values, living a healthy lifestyle and on healthy food this time. The volunteers showed higher carotenoid concentrations than found in previous studies. A significant correlation of healthy lifestyle habits and a high antioxidant status could be determined. Subjects improved their nutritional habits and significantly increased their carotenoid concentration during intervention. Follow-up five months later showed a consolidation of the increase. The investigations show that a healthy diet and a well-balanced lifestyle correlate with a high cutaneous antioxidant concentration and that spectroscopic biofeedback measurement of cutaneous carotenoids as part of an integrated prevention program is a feasible and effective means to raise the health awareness in adolescents.

Palmoplantar Erythrodysesthesia-Like Skin Symptoms in Patients under Various Chemotherapeutics: Preventive and Therapeutic Options

Background/Aims: The palmoplantar erythrodysaesthesia (PPE) is an inflammatory cutaneous side effect in patients under chemotherapy with pegylated liposomal doxorubicin (PLD), with indications that also other chemotherapeutics induce similar side effects. Recently, it has been demonstrated that PLD escapes with the sweat onto the skin inducing radical-forming processes that damage the skin. The topical application of antioxidants with a high radical protection factor has proven to be a very efficient prevention strategy for PLD-treated patients. Methods: 68 patients, who had been treated with 12 different chemotherapeutics and experienced side effects similar to PPE, were treated with a meanwhile commercially available ointment. Results: At the beginning of the therapy, 46 patients suffered from a PPE of severity grade III, while in 22 patients a PPE of severity grade II was diagnosed. The application of the ointment resulted in a significant improvement of the clinical symptoms and the skin status in all these patients; their chemotherapies could be continued. Conclusion: The obtained results suggest that radical-forming processes play an essential role in a great number of chemotherapeutics which induce dermal side effects. The topical application of the antioxidant-containing ointment proved to be a good therapeutic option which needs further evaluation.

Body regions have an impact on the collagen/elastin index of the skin measured by non-invasive in vivo vertical two photon microscopy.

It is known that the collagen and elastin fibre structures are changing with age. There is little knowledge about the influence of body area as these investigations have been limited for ethical reasons, so far. Thus, modified non‐invasive two‐photon microscopy was used providing vertical optical sections of second harmonic generation and autofluorescence to calculate the collagen‐to‐elastin ratio and its alterations depending on the investigated body site in vivo. The results of this study indicate that the impact of different body areas could be higher than the influence of age and should be considered in future studies.

Detection of capecitabine (Xeloda®) on the skin surface after oral administration.

Abstract. Palmoplantar erythrodysesthesia (PPE), or hand-foot syndrome, is a cutaneous toxicity under various chemotherapeutics contributing to the most frequent side effects in patients treated with capecitabine (Xeloda®). The pathomechanism of PPE has been unclear. Here, the topical detection of capecitabine in the skin after oral application was shown in 10 patients receiving 2500  mg/m2/day capecitabine. Sweat samples were taken prior to and one week after oral administration of capecitabine. Using high-resolution continuum source absorption spectrometry, the changes in concentrations of fluorine, which is an ingredient of capecitabine, were quantified and statistically analyzed. Here, we show an increase in fluorine concentrations from 40±10  ppb (2±0.5  pM) before capecitabine administration to 27.7±11.8  ppm (14.6±6.5  nM) after application, p<0.001. The results show the secretion of capecitabine on the skin surface after oral administration, indicating a local toxic effect as a possible pathomechanism of PPE.

Influence of Mechanical Stress on Palmoplantar Erythrodysesthesia - a Case Report

Background: Cutaneous adverse events can have an important negative influence on quality of life and compliance in affected patients. Palmoplantar erythrodysesthesia (PPE; hand-foot syndrome) is a cutaneous toxicity associated with chemotherapeutic treatment, which necessitates treatment interruption or dose reduction in severe cases. This case report of pegylated liposomal doxorubicin-induced PPE shows the influence of mechanical stress on the development of skin lesions in various locations and the importance of patient education and compliance. Case Report: We present the case of a 43-year-old female patient diagnosed with ovarian cancer and having undergone surgical and chemotherapeutic treatment. The development of extensive grade 3 PPE affecting numerous areas of the body particularly exposed to mechanical pressure necessitated dermatological treatment. The combination of local application of an antioxidant-containing ointment and the patients compliance made it possible to continue chemotherapy without interruption or dose reduction. Conclusion: The development of PPE often limits the use of chemotherapeutic agents, and this case report can provide a possible therapeutic and preventive strategy for affected patients.