Scalp microbiome composition changes and pathway evaluations due to effective treatment with Piroctone Olamine shampoo.

OBJECTIVE: To characterize the scalp microbial composition, function, and connection to dandruff severity using a metagenomics approach and to understand the impact of a Piroctone Olamine containing anti-dandruff shampoo on the scalp microbiome. METHODS: Shotgun metagenomics was used to characterize the composition of the scalp microbiomes from 94 subjects with and without clinically defined dandruff. Furthermore, the microbiome of the scalps of 100 dandruff sufferers before and after 3 weeks of treatment with either control or anti-dandruff shampoo containing 0.5% Piroctone Olamine (PO) was characterized and compared to identify microorganisms associated with the dandruff condition and the associated pathways and processes that may contribute to PO's effect on scalp microbiome. RESULTS: A higher relative abundance of Malassezia restricta and Staphylococcus capitis and a lower abundance of Cutibacterium acnes were associated with the dandruff scalps relative to the no-dandruff scalps. A 3-week PO shampoo treatment reduced the relative abundance of Malassezia species and Staphylococcus capitis and increased the relative abundance of Cutibacterium acnes. This change to the scalp microbiome composition is consistent with a return to a healthy no-dandruff microbiome and improved clinical signs and symptoms as measured by adherent scalp flaking score (ASFS) compared with the control shampoo. Functional genomics analysis showed that the PO shampoo treatment reduced oxidative stress-associated genes and decreased the abundance of protease, urease, and lipase genes. These changes correlated positively to improvements in dandruff severity. PO treatment favourably shifted scalp microbiomes in dandruff subjects toward the no-dandruff state. CONCLUSION: Our results suggest that part of the aetiology of dandruff can be attributed to dysbiosis of the scalp microbiome. PO treatment can restore a healthier microbiome, reducing oxidative stress and promoting better scalp health.

OBJECTIF: Caractériser la composition microbienne du cuir chevelu, sa fonction et son lien avec la sévérité des pellicules à l'aide d'une approche métagénomique. Comprendre l'impact d'un shampooing antipelliculaire à base de piroctone olamine sur le microbiome du cuir chevelu. MÉTHODES: La métagénomique shotgun a été utilisée pour caractériser la composition des microbiomes du cuir chevelu de 94 sujets avec et sans pellicules définies cliniquement. Par ailleurs, le microbiome des cuirs chevelus de 100 personnes ayant des pellicules avant et après trois semaines de traitement par un shampooing témoin ou un shampooing antipelliculaire contenant 0,5 % de piroctone olamine (PO) a été caractérisé et comparé pour identifier les micro­organismes associés à l'état pelliculaire, et les voies et processus associés pouvant contribuer à l'effet de la PO sur le microbiome du cuir chevelu. RÉSULTATS: Une abondance relative plus élevée de Malassezia restricta et de Staphylococcus capitis, et une abondance plus faible de Cutibacterium acnes étaient associées aux cuirs chevelus avec des pellicules par rapport aux cuirs chevelus sans pellicules. Un traitement avec un shampooing contenant de la PO de 3 semaines a réduit l'abondance relative des espèces Malassezia et Staphylococcus capitis, et a augmenté l'abondance relative de Cutibacterium acnes. Cette modification de la composition du microbiome du cuir chevelu est cohérente avec un retour à un microbiome sain sans pellicules, et une amélioration des signes et symptômes cliniques mesurés par le score de desquamation du cuir chevelu adhérent (Adherent Scalp Flaking Score, ASFS) par rapport au shampooing témoin. L'analyse génomique fonctionnelle a montré que le traitement avec un shampooing contenant de la PO réduisait les gènes associés au stress oxydatif et diminuait l'abondance des gènes de la protéase, de l'uréase et de la lipase. Ces modifications étaient corrélées positivement à des améliorations de la sévérité des pellicules. Le traitement avec la PO a favorisé l'évolution des microbiomes du cuir chevelu des sujets ayant des pellicules vers un état sans pellicules. CONCLUSION: Nos résultats suggèrent qu'une partie de l'étiologie des pellicules peut être attribuée à la dysbiose du microbiome du cuir chevelu. Le traitement avec la PO peut rétablir un microbiome plus sain, en réduisant le stress oxydatif et en favorisant une meilleure santé du cuir chevelu.

Malassezia restricta-mediated Lipoperoxidation: A Novel Trigger in Dandruff.

Dandruff is a common scalp disorder with multiple microbial and host-related factors contributing to its aetiology, including alterations in scalp sebum. Despite existing evidence that the yeast Malassezia restricta plays a key role in the onset of dandruff, the interplay of these factors is poorly understood. Recently, squalene monohydroperoxide and malondialdehyde were established as biomarkers of dandruff-afflicted scalp, highlighting the role of sebum lipoperoxidation in the triggering and maintenance of dandruff, although its mechanism of action is unknown. The current study provides evidence that M. restricta mediates sebum peroxidation, leading to production of squalene monohydroperoxide and malondialdehyde. Furthermore, in vitro data show that these lipoperoxidation products act on epidermal cells and alter the skin barrier. These results support the role of Malassezia restricta-induced lipoperoxides as triggers of dandruff, which suggests that blocking their production could be a novel anti-dandruff treatment approach.

Clinical evaluation of paraprobiotic-associated Bifidobacterium lactis CCT 7858 anti-dandruff shampoo efficacy: A randomized placebo-controlled clinical trial.

OBJECTIVE: The microbiome plays an important role in a wide variety of skin disorders. Hence, dysbiosis in the skin and/or gut microbiome is associated with an altered immune response, promoting the development of skin diseases, such as atopic dermatitis, psoriasis, acne vulgaris and dandruff. Studies have shown that paraprobiotics may be promising for the treatment of skin disorders through microbiota modulation and immunomodulation. So, the objective is to develop an anti-dandruff formulation using a paraprobiotic (Neoimuno) as active ingredient. METHODS: Randomized, double-blind, placebo-controlled clinical trial was performed in patients who had any degree of dandruff. A total of 33 volunteers were recruited and randomly divided into two groups: placebo or treated. (1% Neoimuno). The ingredient used was Neoimuno (Bifidobacterium lactis strain CCT 7858). Combability analysis and perception questionnaire were applied before and after treatment. Statistical analyses were performed. RESULTS: No adverse effects were reported by patients throughout the study. Through the combability analysis, a significant decrease in the number of particles was verified after 28 days of shampoo use. Regarding perception, there was a significant difference for the cleaning variables and improvement of the general appearance 28 days after the intervention. There were no significant differences for the itching and scaling parameters, as well as the perception parameters at 14 days. DISCUSSION: Topical application of the paraprobiotic shampoo containing 1% Neoimuno was able to significantly improve the feeling of cleanliness and general aspects of dandruff, in addition to reducing scalp flakiness. Thus, with the results obtained through the clinical trial, Neoimuno presents itself as a natural, safe and effective ingredient in the treatment of dandruff. The efficacy of Neoimuno in dandruff was visible within 4 weeks.

OBJECTIF: Le microbiome joue un rôle important dans une grande variété de troubles cutanés. Ainsi, la dysbiose du microbiome cutané et/ou intestinal est associée à une réponse immunitaire altérée, favorisant le développement de maladies cutanées, telles que la dermatite atopique, le psoriasis, l'acné vulgaire et les pellicules. Des études ont montré que les paraprobiotiques peuvent être prometteurs pour le traitement des troubles cutanés par la modulation du microbiote et l'immunomodulation. Ainsi, l'objectif est de développer une formulation antipelliculaire utilisant un paraprobiotique (Neoimuno) comme principe actif. MÉTHODES: Un essai clinique randomisé, en double aveugle et contrôlé par placebo a été réalisé chez des patients présentant des pellicules de n'importe quel degré. Au total, 33 volontaires ont été recrutés et divisés au hasard en deux groupes: placebo ou traité. (1% Neoimuno). L'ingrédient utilisé était le Neoimuno (souche Bifidobacterium lactis CCT 7858). Une analyse de combabilité et un questionnaire de perception ont été appliqués avant et après le traitement. Des analyses statistiques ont été effectuées. RÉSULTATS: Aucun effet indésirable n'a été signalé par les patients tout au long de l'étude. Grâce à l'analyse de combabilité, une diminution significative du nombre de particules a été vérifiée après 28 jours d'utilization du shampooing. Concernant la perception, il y avait une différence significative pour les variables de nettoyage et d'amélioration de l'aspect général 28 jours après l'intervention. Il n'y avait pas de différences significatives pour les paramètres de démangeaison et de desquamation, ainsi que les paramètres de perception à 14 jours. DISCUSSION: L'application topique du shampooing paraprobiotique contenant 1% de Neoimuno a pu améliorer significativement la sensation de propreté et les aspects généraux des pellicules, en plus de réduire la desquamation du cuir chevelu. Ainsi, avec les résultats obtenus grâce à l'essai clinique, Neoimuno se présente comme un ingrédient naturel, sûr et efficace dans le traitement des pellicules. L'efficacité de Neoimuno sur les pellicules a été visible en 4 semaines.

Characterization of piroctone olamine for topical delivery to the skin.

OBJECTIVE: Dandruff and its more severe related condition, seborrheic dermatitis affects a high proportion of the population at some point in their life. Piroctone olamine, also known as Octopirox® (OPX) is the monoethanolamine salt of piroctone and is an antifungal agent widely used for the management of dandruff. The aim of the present work was to characterize the physicochemical properties of piroctone olamine and to conduct pre-formulation studies for the development of novel topical formulations of this active. METHODS: An HPLC method was developed and validated for the analysis of OPX. The melting point was determined using the DSC Q2000 (TA Instruments, USA). The distribution coefficient (logD(O/PBS) ) and partition coefficient (log Po/w ) was determined in phosphate-buffered saline (PBS) AND deionized (DI) water using the shake flask method. All experiments were performed at room temperature. The solubility was determined experimentally by adding amount of active to a solvent. The samples were kept at 32° ± 1°C for 48 h in a water bath. The stability of the compound was determined in a range of solvents by preparing solutions of 1 mg mL-1 in the relevant solvents. These solutions were kept and stirred throughout the experiment at 32 ± 1°C, and aliquots were taken at 24, 48 and 96 h. RESULTS: The HPLC method was developed successfully; however, samples at the lower end of the calibration curve showed lower degrees of precision and accuracy. Based on experiments with DSC, the melting point was observed at an onset temperature of 132.4°C. The LogD was determined to be 1.84. The compound had the highest solubility in methanol (278.4 mg mL-1 ) and propylene glycol (PG), with a value of 248.8 mg mL-1 . The lowest solubility for OPX was in dimethyl isosorbide (9.9 mg mL-1 ), Labrafac™ (3.6 mg mL-1 ) and isostearyl isostearate (0.5 mg mL-1 ). Over the 4 days, OPX showed stability in ethanol and PG, while a notable decrease in OPX was observed in PBS and DI water at 32 ± 1°C. CONCLUSION: The physicochemical properties of OPX were characterized to find suitable excipients able to target the epidermis for topical delivery. Building on these findings, future work will focus on the development of novel topical formulation of OPX.

OBJECTIF: la production de pellicules et la maladie plus grave qui y est apparentée, la dermatite séborrhéique, touchent une grande partie des personnes à un moment donné de leur vie. La piroctone olamine, également connue sous le nom d'Octopirox® (OPX), est le sel de monoéthanolamine de la piroctone. Il s'agit d'un agent antifongique largement utilisé pour le traitement des pellicules. L'objectif de ce travail était de caractériser les propriétés physicochimiques de la piroctone olamine et de mener des études de préformulation pour le développement de nouvelles formulations topiques de ce principe actif. MÉTHODES: une méthode de chromatographie liquide à haute performance (CLHP) a été développée et validée pour l'analyse de l'OPX. Le point de fusion a été déterminé à l'aide du calorimètre à balayage différentiel (Differential Scanning Calorimetry, DSC) Q2000 (TA Instruments, États-Unis). Le coefficient de distribution (logD(Octanol/PBS) ) et le coefficient de partage (log Poctanol/eau , ou log Poe ) ont été déterminés dans le tampon phosphate salin (phosphate buffered saline, PBS) et dans l'eau désionisée (deionised, DI) à l'aide de la méthode par agitation en flacon. Toutes les expériences ont été réalisées à température ambiante. La solubilité a été déterminée de manière expérimentale. Une certaine quantité du principe actif a été ajoutée au solvant. Les échantillons ont été conservés à une température de 32 °C ± 1 °C pendant 48 h dans un bain-marie. La stabilité du composé a été déterminée à l'aide d'une gamme de solvants. Des solutions de 1 mg mL−1 ont été préparées dans les solvants correspondants. Les solutions ont été conservées et agitées tout au long de l'expérience à une température de 32°C ± 1°C. Des aliquotes ont été prélevées après 24, 48 et 96 h. RÉSULTATS: la méthode CLHP a été développée avec succès. Toutefois, les échantillons situés dans la partie inférieure de la courbe d'étalonnage ont montré des degrés inférieurs de précision et d'exactitude. Sur la base des expériences avec le DSC, le point de fusion a été observé à une température initiale de 132,4°C. Le LogD a été déterminé à 1,84. Le composé présentait la solubilité la plus élevée dans le méthanol (278,4 mg mL−1 ) et le propylène glycol (PG), avec une valeur de 248,8 mg mL−1 . L'OPX présentait la solubilité la plus faible dans l'isosorbide de diméthyle (9,9 mg.mL−1 ), le LabrafacTM (3,6 mg mL−1 ) et l'isostéarate d'isostéaryle (0,5 mg mL−1 ). Sur les 4 jours, l'OPX a montré une stabilité dans l'éthanol et le PG, tandis qu'il a diminué de manière notable dans le PBS et l'eau désionisée à une température de 32°C ± 1°C. CONCLUSION: les propriétés physicochimiques de l'OPX ont été caractérisées afin de trouver des excipients appropriés capables de cibler l'épiderme dans le cadre d'une administration topique. En s'appuyant sur ces résultats, les travaux futurs se concentreront sur le développement d'une nouvelle formulation topique de l'OPX.

Enhanced piroctone olamine retention from shampoo for superior anti-dandruff efficacy.

BACKGROUND: Dandruff is a pervasive chronic condition which negatively impacts quality of life. Effective treatment requires efficient delivery of scalp benefit agents that control commensal scalp Malassezia levels. Delivery of benefit agents from shampoos requires balancing many technical parameters to achieve the desired outcome without sacrificing secondary parameters, such as cosmetic attributes. AIM: To develop formulation technologies that increase the shampoo delivery efficiency of the scalp benefit agent piroctone olamine (PO). Increased delivery should result in increased anti-dandruff efficacy. METHODS: Micellar Stability and Association parameters were quantified via dynamic surface tension and nuclear magnetic resonance (NMR) diffusion parameters, respectively. PO delivery has been assessed in vivo both on the scalp surface and follicular infindibula using extraction procedures and analytical analysis. Clinical anti-dandruff efficacy was assessed for an advanced delivery technology prototype in comparison to standard delivery technology. RESULTS: Shampoo prototypes have been developed that increase the delivery efficiency of PO. Both surfactant and polymer coacervate-based approaches have been developed. Decreased micellar stability results in weaker association between PO and micelles, resulting in more efficient PO retention on the scalp surface and delivery to the infundibula. Increased charge density of cationic polymers optimizes coacervation enabling improved PO delivery as well. Increased PO delivery has been shown clinically to result in higher anti-dandruff efficacy as measured by both visible flakes and underlying biomarkers. CONCLUSION: Increased efficiency PO delivery shampoos have been developed by optimization of both surfactant and coacervate parameters. The increased deposition efficiency results in significantly more products with significantly greater anti-dandruff efficacy.

CONTEXTE: Les pellicules sont une maladie chronique omniprésente qui a un impact négatif sur la qualité de vie. Un traitement efficace nécessite une administration efficace d'agents bénéfiques pour le cuir chevelu qui contrôlent les niveaux commensaux de Malassezia. L'administration d'agents bénéfiques à partir de shampooings nécessite d'équilibrer de nombreux paramètres techniques pour obtenir le résultat souhaité sans sacrifier des paramètres secondaires tels que les attributs cosmétiques. BUT: Développer des technologies de formulation qui augmentent l'efficacité d'administration du shampooing de l'agent bénéfique pour le cuir chevelu piroctone olamine (PO). Une livraison accrue devrait entraîner une efficacité antipelliculaire accrue. MÉTHODES: La stabilité micellaire et les paramètres d'association ont été quantifiés via les paramètres de tension superficielle dynamique et de diffusion RMN, respectivement. L'administration de PO a été évaluée in vivo à la fois sur la surface du cuir chevelu et sur l'indibula folliculaire à l'aide de procédures d'extraction et d'analyses analytiques. L'efficacité antipelliculaire clinique a été évaluée pour un prototype de technologie d'administration avancée par rapport à la technologie d'administration standard. RÉSULTATS: Des prototypes de shampooing ont été développés pour augmenter l'efficacité de livraison des PO. Des approches à base de tensioactifs et de coacervats polymères ont été développées. Une diminution de la stabilité micellaire entraîne une association plus faible entre le PO et les micelles, ce qui entraîne une rétention plus efficace du PO sur la surface du cuir chevelu et une livraison à l'infundibula. L'augmentation de la densité de charge des polymères cationiques optimise la coacervation, permettant également une meilleure administration de PO. Il a été démontré cliniquement que l'augmentation de l'administration de PO entraîne une efficacité antipelliculaire plus élevée, mesurée à la fois par les squames visibles et les biomarqueurs sous-jacents. CONCLUSION: Des shampooings à libération de PO à efficacité accrue ont été développés en optimisant à la fois les paramètres du tensioactif et du coacervat. L'efficacité de dépôt accrue se traduit par beaucoup plus de produits avec une efficacité antipelliculaire nettement supérieure.

Clinical efficacy of a gentle anti-dandruff itch-relieving shampoo formulation.

Dandruff is a common scalp condition affecting almost half of the world's population. Despite its high prevalence, the exact pathophysiology is not well established and is understood to be multifactorial, with factors such as fungal colonization, sebaceous gland activity and individual factors being implicated. There is a need for an effective and safe shampoo that can target the above factors. Hence, we have developed a shampoo formulation with properties of oil control, moisturizing, non-irritative, anti-fungal, anti-microbial and itch-relieving. In this interventional, open-label study, we evaluated the efficacy and safety of this shampoo in reducing the clinical signs of dandruff and pruritus in patients with pre-existing mild-to-moderate dandruff over a course of 21-day treatment duration through self-assessment and objective clinical evaluations. After continued use of the shampoo, there was a significant decrease in the adherent and loose scalp flaking scores. Mean pruritus scores also decreased significantly across the 21-day time points. There were also no adverse events or skin intolerances reported. This study showed that our shampoo formulation has led to a significant reduction in both adherent and loose scalp flaking and pruritus when used in individuals suffering from mild to moderate dandruff. As such, it is an ideal shampoo, which can be used to effectively control dandruff.

Les pellicules sont une affection courante du cuir chevelu qui touche près de la moitié de la population mondiale. Malgré sa prévalence élevée, la physiopathologie exacte n'est pas bien établie et est comprise comme étant multifactorielle, avec des facteurs impliqués tels que la colonisation fongique, l'activité des glandes sébacées et des facteurs individuels. Un shampooing sûr et efficace pouvant cibler les facteurs évoqués ci-dessus est nécessaire. Par conséquent, nous avons développé une formulation de shampooing présentant des propriétés de contrôle du sébum, d'hydratation, non irritante, antifongique, antimicrobienne et de soulagement des démangeaisons. Dans cette essaie interventionnelle ouvert, nous avons évalué l'efficacité et la sécurité d'emploi de ce shampooing dans la réduction des signes cliniques de pellicules et de prurit chez des patients présentant des pellicules préexistantes légères à modérées sur une durée de traitement de 21 jours par le biais d'auto-évaluations et d'évaluations cliniques objectives. Après une utilisation continue du shampooing, une diminution significative des scores de squames adhérents et d'excoriation du cuir chevelu a été observée. Les scores de prurit moyens ont également significativement diminué tout au long de la période de 21 jours. De même, aucun événement indésirable ou intolérance cutanée n'a été rapporté. Cette étude a montré que notre formulation de shampooing a entraîné une réduction significative des squames adhérents, de l'excoriation du cuir chevelu et du prurit lorsqu'elle est utilisée chez des personnes souffrant de pellicules légères ou modérées. Il s'agit donc d'un shampooing idéal qui peut être utilisé pour contrôler efficacement les pellicules.

Ketoconazole beyond antifungal activity: Bioinformatics-based hypothesis on lipid metabolism in dandruff and seborrheic dermatitis.

The role of Malassezia yeasts in dandruff and seborrheic dermatitis is unclear; however, antifungal therapy with ketoconazole is commonly used. We propose that ketoconazole shifts skin lipid profile, affects Malassezia lipid metabolism and favours biotin-producing bacteria. Biotin regulates inflammatory response and cell proliferation, contributing to symptom improvement.

Comparison of whole-head and split-head design for the clinical evaluation of anti-dandruff shampoo efficacy.

OBJECTIVE: Dandruff is a common scalp condition that can be improved by regular use of shampoos containing anti-fungal actives. The efficacy of anti-dandruff shampoos can be assessed by measuring scalp flaking, one of the important dandruff symptoms. A randomized, double-blind trial is often used with one of two clinical designs: whole-head parallel design and split-head paired design. We aimed to explore the difference in product differentiation between these two designs using the same two test shampoos and the same scalp flaking assessment method (Total Weighted Head Score Adhered Flakes-TWHS AF). METHODS: A clinical study was conducted with a 2- to 3-week wash-out phase and a 4-week test phase, consisting of 2 cells: 120 subjects with whole-head parallel design, divided into 2 subgroups (1:1) using on-site controlled washing method (either wash their own hair at a study site, under the instruction of a study supervisor or wash their own hair at home, as per instructions, but without supervision) and 35 subjects with split-head paired design using salon-staff washing method. Both cells employed hair washing at frequency of three times a week and TWHS AF measurement once a week from the baseline assessment. RESULTS: Both designs gave similar differences in TWHS AF between products: 5.6 units (95% CI: 4.1-7.0 units) in whole-head design and 5.9 units (95% CI: 4.9-6.9 units) in split-head design. CONCLUSION: Split-head paired design shows a similar ability of detecting product difference as whole-head parallel design, whereas it is a choice of more efficient and more cost-effective, as only a quarter of the subjects are required to demonstrate the efficacy between anti-dandruff shampoos.

OBJECTIF: Les pellicules sont une affection courante du cuir chevelu qui peut être améliorée par l'utilisation régulière de shampooings contenant des principes actifs antifongiques. L'efficacité des shampooings antipelliculaires peut être évaluée en mesurant la desquamation du cuir chevelu, l'un des symptômes importants associés aux pellicules. Il est souvent fait recours à une étude randomisée et en double aveugle reposant sur l'une des deux conceptions cliniques suivantes: une conception parallèle portant sur la tête entière et une conception appariée par séparation de la surface de la tête. Nous avons cherché à étudier en quoi des produits se différenciaient entre ces deux conceptions, en utilisant les deux mêmes shampooings d'examen et la même méthode d'évaluation de la desquamation du cuir chevelu (score total pondéré des pellicules collées sur la tête [Total Weighted Head Score Adhered Flakes, TWHS AF]). MÉTHODES: Une étude clinique a été menée avec une fenêtre thérapeutique de deux à trois semaines et une phase d'examen de quatre semaines, composée de deux cellules: 120 sujets recrutés selon une conception parallèle portant sur la tête entière, répartis en deux sous-groupes (1:1), avec un lavage réalisé au centre d'après une méthode contrôlée (lavage par le sujet dans l'un des centres de l'étude, réalisé sous les instructions d'un superviseur de l'étude, ou lavage par le sujet à son domicile, en suivant les instructions, mais sans surveillance) et 35 sujets recrutés selon une conception appariée par séparation de la surface de la tête, avec un lavage réalisé selon la méthode employée par le personnel des salons de coiffure. Pour les deux cellules, le lavage des cheveux avait lieu à une fréquence de trois fois par semaine et le score TWHS AF était mesuré une fois par semaine à partir de l'évaluation de référence. RÉSULTATS: Les deux conceptions ont permis d'observer des différences similaires des scores TWHS AF entre les produits: 5,6 unités (IC à 95%: 4,1 à 7,0 unités) avec la conception portant sur la tête entière et 5,9 unités (IC à 95%: 4,9 à 6,9 unités) avec la conception par séparation de la surface de la tête. CONCLUSION: Par comparaison avec la conception parallèle portant sur la tête entière, la conception appariée par séparation de la surface de la tête montre une capacité de détection similaire de la différence entre les produits, mais constitue un choix plus efficace et plus rentable, car elle n'exige de démontrer l'efficacité entre les shampooings antipelliculaires que chez un quart des sujets.

[Malassezia spp.: interactions with topically applied lipids-a review : Malassezia and topically applied lipids]. / Malassezia spp.: Wechselwirkungen mit Lipidbestandteilen von Topika ­ eine Übersicht : Malassezia und Topika.

Lipophilic Malassezia yeasts are an important part of the human resident skin flora, especially in seborrheic areas. Besides mutualistic interactions with the host they are also linked to diseases although the specific causes are not yet comprehensively understood. The amount of available lipids on the skin correlates with the Malassezia density and also with the occurrence of certain diseases like tinea versicolor. Here, the naturally produced lipids of the sebaceous glands play a role. Hardly studied thus far is the impact of topically applied lipids. Here, growth promotion as well as inhibition of Malassezia cells as well as the production of new metabolites through ester cleavage are possible. One example is the release of antimicrobial fatty acids from hydroxypropyl caprylate through the action of Malassezia lipases. This "self-kill" principle results in the reduction of the amount of Malassezia cells and can be applied as new therapy option for dandruff treatment. A better understanding of the interaction between topica and Malassezia would increase their skin tolerance and open new therapy options.

Turning autophobic wetting on biomimetic surfaces into complete wetting by wetting additives.

Autophobicity or pseudo partial wetting, a phenomenon of a liquid not spreading on its own monolayer, is characterized by an energy barrier that prevents the growth of a wetting film beyond the monolayer thickness. Applying a molecularly detailed self-consistent field theory we illustrate how autophobic wetting can be overcome by wetting additives. More specifically we use an emulsifier which keeps the interfacial tension between the wetting component and the majority solvent low, and a co-solvent additive which partitions inside the film and then destroys the molecular order in it so that the barrier for film growth is cleared. An application wherein it is believed that autophobic wetting is counteracted by such a set of wetting additives is found in an antidandruff shampoo formulation. We have experimental results that show thick deposits onto hydrophobic hair surfaces by administration of the antidandruff shampoo. The complementary modeling of such a system suggests that the active ingredient plays the role of the co-solvent additive. As significant amounts of the co-solvent additives are needed to approach the completely wet state, the formulation naturally brings large amounts of active ingredient to the root of the hair where its presence is required.

Etiology and treatment of dandruff according to Persian medicine.

Scalp dandruff is one of the most common complaints of patients visiting dermatologic clinics. It has significant influence on the self-confidence and social image of the individuals it affects. The current study aimed to analyze this problem from the viewpoint of Persian medicine. This paper is a literature review in which the text of selected books on Persian medicine is investigated using content analysis based on the theoretical sampling method. The studied keywords in the Persian medicine books included Hozaz, Ebrieh, and Ghooba. Relevant points were extracted from the text of papers selected from PubMed, Scopus, and SID and analyzed further. Persian medicine considers the incidence of scalp dandruff to be an output of the interaction between internal and external factors and concentrates more on disorder in the process of waste removal through the skin and its role in the development of scaling diseases. In order to dandruff treatment, Persian medicine sages considered nutrition, personal hygiene, status of the digestive system, and the health status of other organs in addition to topical treatment. Clinical examination of Persian medicine hypotheses, especially how the quality of skin secretions affects the development of scaly skin, can improve the treatment of scalp dandruff and other scaling skin diseases.

The myrtus communis L. solution versus ketoconazole shampoo in treatment of dandruff: A double blinded randomized clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of myrtus communis L. solution in the treatment of dandruff and to compare it with ketoconazole. METHODS: This double-blind randomised clinical trial was conducted at Shiraz University of Medical Sciences, Shiraz, Iran, from December 2015 to August 2016, and comprised patients with dandruff aged 18-60 years visiting the dermatology out-patient clinic. The subjects were randomised into two equal groups. The treatment group received myrtus communis L. solution and a placebo shampoo, while the control group received ketoconazole shampoo and a placebo solution. The total duration of the study for each subject was one month and subjects in both groups used their respective interventions 8 times during that period. The parameters studied were pruritus, erythema, severity of scaling, and the extent of scalp involvement. All subjects underwent scalp scaling tests at the beginning, after 10 days and at the end of the 30th day. SPSS 21 was used for data analysis. RESULTS: Of the 90 individuals, there were 45(50%) in each of the two groups. However, 74(82%) subjects completed the third visit and, of them, there were 37(50%) in each group. Both groups showed significant improvement in all outcome measures (p<0.001). There were no significant differences between the groups in terms of efficacy, satisfaction rate and side effects (p>0.05 for each outcome). CONCLUSIONS: Myrtus solution was found to be effective in the treatment of dandruff.

Inhibition of Malassezia globosa carbonic anhydrase with phenols.

A panel of 22 phenols was investigated as inhibitors of the ß-class carbonic anhydrase (CAs, EC 4.2.1.1) from the fungal parasite Malassezia globosa (MgCA), a validated anti-dandruff drug target. The displayed inhibitory activities were compared to the ones previously reported against the off-target widely distributed human (h) isoforms hCA I and II. All tested phenols possessed a better efficacy in inhibiting MgCA than the clinically used sulfonamide acetazolamide, with KIs in the range of 2.5 and 65.0µM. A homology-built model of MgCA was also used for understanding the binding mode of phenols to the fungal enzyme. Indeed, a wide network of hydrogen bonds and hydrophobic interactions between the phenol and active site residues were evidenced. The OH moiety of the inhibitor was observed anchored to the zinc-coordinated water, also making hydrogen bonds with Ser48 and Asp49. The diverse substituents at the phenolic scaffold were observed to interact with different portions of the hydrophobic pocket according to their nature and position. Considering the effective MgCA inhibitory properties of phenols, beside to the rather low inhibition against the off-target hCA I and II, this class of compounds might be of considerable interest in the cosmetics field as potential anti-dandruff drugs.

Evaluation of therapeutic potential of VB-001, a leave-on formulation, for the treatment of moderate adherent dandruff.

BACKGROUND: Dandruff is a common scalp condition characterized by excessive scaling and itch. Aberrant colonization of the scalp by commensal Malassezia spp. is a major contributor in the multifactorial etiology of dandruff. Literature based understanding of Malassezia linked pathophysiology of dandruff allowed us to comprehend a strategy to potentiate the efficacy of a known antifungal agent used in dandruff therapy. The aim of this study was to determine the efficacy and skin safety of VB-001 antidandruff leave-on formulation in comparison with marketed antidandruff ZPTO shampoo in patients with moderate adherent dandruff of the scalp. METHODS: Healthy males or females aged ≥ 15 years and ≤ 65 with a clinical diagnosis of moderate adherent dandruff of the scalp were recruited for the study to monitor the effects of topical VB-001 versus those of marketed antidandruff ZPTO shampoo. RESULTS: 168 subjects were randomized to the treatment (VB-001, n = 84) and control (ZPTO shampoo, n = 84) groups. The efficacy of each product was evaluated by comparing proportion of subjects who have shown reduction in flaking by ASFS (adherent scalp flaking score) and pruritus by IGA (investigator global assessment) score. VB-001 imparted consistently better reduction in ASFS and enabled early reduction of pruritus in comparison to marketed ZPTO shampoo. CONCLUSION: VB-001, a leave-on formulation with ingredients chosen to selectively disturb the Malassezia niche on dandruff scalp by denying extra nutritional benefits to the microbe, provides unique advantages over existing best in class ZPTO shampoo therapy. It has the potential to emerge as an attractive novel treatment for moderate adherent dandruff. TRIAL REGISTRATION: CTRI Registration number: CTRI/2013/01/003283 . Registered on: 02/01/2013.

New targets in the battle against dandruff.

Dandruff is a scalp disorder characterized by flaking skin and itch of an excessive oily scalp skin. It affects 55% of the global youth and adult population. Seborrheic dermatitis is a similar scalp skin disorder with aggravated itchy rashes and flaking. Different factors are identified in the dandruff development: increased sebum production, uncontrolled fungal growth of Malassezia strains and individual reaction to pro-inflammatory environment, and the susceptibility to trigger an immunological response. Using in vitro and ex vivo models, we show that an Epilobium angustifolium extract dose dependently reduces lipid synthesis in sebocytes to a maximum of -43% (1% extract), and protects the epidermis from Malassezia-induced morphological changes. Epilobium angustifolium extract also acts through innovative mechanisms involving regulations of defensins (human beta-defensins [hBD2] and hBD3) and toll-like receptor 2 involved in the immunological response of the skin. The anti-dandruff and sebum-regulating efficacy of E. angustifolium extract (1.5%) was confirmed in a clinical study that mobilized 24 volunteers with dandruff and greasy scalp for 30 days. At the end of the study, nonadherent and adherent dandruffs were significantly (p < 0.0001) reduced in average by -54% and -48%, respectively. Using Sebumeter® measurements, scalp sebum production was inhibited by -67% (p < 0.0001) in average over baseline. In conclusion, E. angustifolium extract offers a new innovative approach to dandruff reduction through immunomodulation of the skin response to Malassezia invasion.

Carbonic anhydrase activators: Activation of the ß-carbonic anhydrase from Malassezia globosa with amines and amino acids.

The ß-carbonic anhydrase (CA, EC 4.2.1.1) from the dandruff producing fungus Malassezia globosa, MgCA, was investigated for its activation with amines and amino acids. MgCA was weakly activated by amino acids such as L-/D-His, L-Phe, D-DOPA, D-Trp, L-/D-Tyr and by the amine serotonin (KAs of 12.5-29.3µM) but more effectively activated by d-Phe, l-DOPA, l-Trp, histamine, dopamine, pyridyl-alkylamines, and 4-(2-aminoethyl)-morpholine, with KAs of 5.82-10.9µM. The best activators were l-adrenaline and 1-(2-aminoethyl)piperazine, with activation constants of 0.72-0.81µM. This study may help a better understanding of the activation mechanisms of ß-CAs from pathogenic fungi as well as the design of tighter binding ligands for this enzyme which is a drug target for novel types of anti-dandruff agents.

In silico modeling of ß-carbonic anhydrase inhibitors from the fungus Malassezia globosa as antidandruff agents.

A quantitative structure-activity relationship (QSAR) study of sulfonamide inhibitors targeting the ß-carbonic anhydrase (CA, EC 4.2.1.1) from the fungus Malassezia globosa is reported. A large set of PRECLAV descriptors has been used to obtain four parametric models. This study presents QSAR data on a pool of 28 compounds. The quality of prediction is high enough (SE = 0.3446, r(2) = 0.8687, F = 39.6921, Q = 0.7446). A heuristic algorithm selected the best multiple linear regression (MLR) equation which showed the correlation between the observed values and the calculated values of activity. The proposed prediction set included new, not yet synthesized, 23 molecules having various structures. Many compounds in the prediction set seem to possess higher computed activity compared to the presently available M. globosa ß-CA inhibitors.

Zinc Pyrithione: A Topical Antimicrobial With Complex Pharmaceutics.

Zinc pyrithione (ZPT) is an active material that has been used for over 50 years to effectively treat dandruff and seborrheic dermatitis (D/SD). It has become the most common material for that purpose, its use has expanded to include other skin benefits such as skin hygiene. However, there is much about ZPT that is unappreciated. It is a rationally developed molecule that was modeled after the naturally occurring antimicrobial aspergillic acid. The molecular basis for its antifungal activity has been elucidated. The efficacy of ZPT originates from two attributes. First, it has a very broad antimicrobial spectrum of activity, including fungi, gram-positive and -negative bacteria. Second, the material has very low solubility, resulting in formulation and delivery as a particulate material, which has distinct performance advantages. The particles are deposited and retained on the target skin surfaces even when delivered from rinse-off products. These particles slowly release molecularly active material to interact with the surface fungal and bacteria cells to control their population, functioning as slow-release reservoirs to provide extended and persistent benefits. This particulate nature, though, results in complex pharmaceutics to realize the full efficacy benefits; it is common to see products with the same ZPT level having widely varying levels of clinical performance. Several product matrix-determined factors directly impact resultant benefits: ZPT must be retained on the skin surface achieving uniform spatial distribution laterally as well as within hair follicles (especially on scalp); ZPT must be maintained as a physically stable dispersion in product; ZPT must be maintained in a chemically active form as there are many chemical reactions that can occur that can harm ZPT bioactivity. The benefits achievable by employing ZPT require significant pharmaceutics expertise to realize the full benefits of this active material.

[How I treat dandruff using a shampoo with a sulfate-free tensio-active]. / Comment je traite un état pelliculaire par un shampoing à base lavante «sulfate-free¼.

A new formulation of an anti-dandruff shampoo containing a surfactant devoid of a sulfate-type anionic part has been assessed in vivo in 41 subjects. Introducing a welltried agent, the 0.5 % piroctone olamine confers to this shampoo a high anti-dandruff efficacy, a reduction in the density in Malassezia spp, as well as a good remanence after shampoo. In addition, piroctone olamine appears to influence the sebum rheology by reducing the hair greasing.

Une nouvelle formulation d'un shampoing antipelliculaire, basée sur l'utilisation de tensio-actifs sans groupe anionique de type sulfate («sulfate free¼) a été évaluée in vivo sur 41 sujets. L'introduction d'un agent éprouvé, la piroctone olamine à 0,5 %, confère à ce shampoing une efficacité antipelliculaire élevée, une réduction de la densité de Malassezia spp, ainsi qu'une bonne rémanence de l'effet après shampoing. La piroctone olamine semble, de plus, modifier la rhéologie du sébum en ralentissant le phénomène de regraissage des cheveux.

Anion inhibition studies of the dandruff-producing fungus Malassezia globosa ß-carbonic anhydrase MgCA.

The genome of the fungal parasite Malassezia globosa, the causative agent of dandruff, contains a single gene annotated as encoding a carbonic anhydrase (CAs, EC 4.2.1.1) belonging to the ß-class (MgCA). In an earlier work (J. Med. Chem. 2012, 55, 3513) we have validated this enzyme as an anti-dandruff drug target, reporting that sulfonamide inhibitors show in vitro and in vivo effects, in an animal model of Malassezia infection. However, few classes of compounds apart the sulfonamides, were investigated for their activity against MgCA. Here we present an anion inhibition study of this enzyme, reporting that metal complexing anions such as cyanate, thiocyanate, cyanide, azide are weak MgCA inhibitors (KIs ranging between 6.81 and 45.2 mM) whereas bicarbonate (KI of 0.59 mM) and diethyldithiocarbamate (KI of 0.30 mM) together with sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid were the most effective inhibitors detected so far, with KIs ranging between 83 and 94 µM. This study may help a better understanding of the inhibition profile of this enzyme and may offer the possibility to design new such modulators of activity belonging to different chemical classes.