Seborrheic dermatitis: topical therapeutics and formulation design.

Seborrheic dermatitis (SD) is a common dermatological disorder with symptoms that include skin flaking, erythema and pruritus. This review discusses the topical products available for treating SD, which target several aspects of disease pathobiology, including cutaneous microbial dysbiosis (driven by Malassezia yeast), inflammation, sebum production and skin barrier disruption. Among the various treatments available, zinc pyrithione (ZnPT) based products that exhibit anti-fungal action are the market leaders. A skin compartment approach is presented here for combining ZnPT exposure information with threshold levels for anti-fungal efficacy and toxicity, overall providing a comprehensive picture of ZnPT therapeutics and safety. While Malassezia yeast on the surface are effectively targeted, yeast residing beyond the superficial follicle may not receive adequate ZnPT for anti-fungal effect forming the basis for skin re-colonisation. Levels entering systemic circulation from topical delivery are well below toxic thresholds, however the elevated zinc levels within the viable epidermis warrants further investigation. Strategies to improve formulation design can be broadly classified as influencing 1) topical delivery, 2) therapeutic bioactivity, 3) skin mildness, and 4) sensory attributes. Successful SD treatment ultimately requires formulations that can balance efficacy, safety, and consumer appeal.

Medical school dermatology education: a scoping review.

Dermatological diseases are widespread and have a significant impact on the quality of life of patients; however, access to appropriate care is often limited. Improved early training during medical school represents a potential upstream solution. This scoping review explores dermatology education during medical school, with a focus on identifying the factors associated with optimizing the preparation of future physicians to provide care for patients with skin disease. A literature search was conducted using online databases (Embase, MEDLINE, CINAHL and Scopus) to identify relevant studies. The Joanna Briggs Institute methodological framework for scoping reviews was used, including quantitative and qualitative data analysis following a grounded theory approach. From 1490 articles identified, 376 articles were included. Most studies were from the USA (46.3%), UK (16.2%), Germany (6.4%) and Canada (5.6%). Only 46.8% were published as original articles, with a relatively large proportion either as letters (29.2%) or abstracts (12.2%). Literature was grouped into three themes: teaching content, delivery and assessment. Core learning objectives were country dependent; however, a common thread was the importance of skin cancer teaching and recognition that diversity and cultural competence need greater fostering. Various methods of delivery and assessment were identified, including computer-aided and online, audiovisual, clinical immersion, didactic, simulation and peer-led approaches. The advantages and disadvantages of each need to be weighed when deciding which is most appropriate for a given learning outcome. The broader teaching-learning ecosystem is influenced by (i) community health needs and medical school resources, and (ii) the student and their ability to learn and perform. Efforts to optimize dermatology education may use this review to further investigate and adapt teaching according to local needs and context.

Multi-Modal Imaging to Assess the Follicular Delivery of Zinc Pyrithione.

Zinc pyrithione (ZnPT) is a widely used antifungal, usually applied as a microparticle suspension to facilitate delivery into the hair follicles, where it then dissociates into a soluble monomeric form that is bioactive against yeast and other microorganisms. In this study, we use multiphoton microscopy (MPM) and fluorescence lifetime imaging microscopy (FLIM) to characterise ZnPT formulations and map the delivery of particles into follicles within human skin. To simulate real-world conditions, it was applied using a massage or no-massage technique, while simultaneously assessing the dissolution using Zinpyr-1, a zinc labile fluorescent probe. ZnPT particles can be detected in a range of shampoo formulations using both MPM and FLIM, though FLIM is optimal for detection as it allows spectral and lifetime discrimination leading to increased selectivity and sensitivity. In aqueous suspensions, the ZnPT 7.2 µm particles could be detected up to 500 µm in the follicle. The ZnPT particles in formulations were finer (1.0-3.3 µm), resulting in rapid dissolution on the skin surface and within follicles, evidenced by a reduced particle signal at 24 h but enhanced Zinpyr-1 intensity in the follicular and surface epithelium. This study shows how MPM-FLIM multimodal imaging can be used as a useful tool to assess ZnPT delivery to skin and its subsequent dissolution.

Targeted Delivery of Zinc Pyrithione to Skin Epithelia.

Zinc pyrithione (ZnPT) is an anti-fungal drug delivered as a microparticle to skin epithelia. It is one of the most widely used ingredients worldwide in medicated shampoo for treating dandruff and seborrheic dermatitis (SD), a disorder with symptoms that include skin flaking, erythema and pruritus. SD is a multi-factorial disease driven by microbiol dysbiosis, primarily involving Malassezia yeast. Anti-fungal activity of ZnPT depends on the cutaneous availability of bioactive monomeric molecular species, occurring upon particle dissolution. The success of ZnPT as a topical therapeutic is underscored by the way it balances treatment efficacy with formulation safety. This review demonstrates how ZnPT achieves this balance, by integrating the current understanding of SD pathogenesis with an up-to-date analysis of ZnPT pharmacology, therapeutics and toxicology. ZnPT has anti-fungal activity with an average in vitro minimum inhibitory concentration of 10-15 ppm against the most abundant scalp skin Malassezia species (Malassezia globosa and Malassezia restrica). Efficacy is dependent on the targeted delivery of ZnPT to the skin sites where these yeasts reside, including the scalp surface and hair follicle infundibulum. Imaging and quantitative analysis tools have been fundamental for critically evaluating the therapeutic performance and safety of topical ZnPT formulations. Toxicologic investigations have focused on understanding the risk of local and systemic adverse effects following exposure from percutaneous penetration. Future research is expected to yield further advances in ZnPT formulations for SD and also include re-purposing towards a range of other dermatologic applications, which is likely to have significant clinical impact.

Topical drug delivery: History, percutaneous absorption, and product development.

Topical products, widely used to manage skin conditions, have evolved from simple potions to sophisticated delivery systems. Their development has been facilitated by advances in percutaneous absorption and product design based on an increasingly mechanistic understanding of drug-product-skin interactions, associated experiments, and a quality-by-design framework. Topical drug delivery involves drug transport from a product on the skin to a local target site and then clearance by diffusion, metabolism, and the dermal circulation to the rest of the body and deeper tissues. Insights have been provided by Quantitative Structure Permeability Relationships (QSPR), molecular dynamics simulations, and dermal Physiologically Based PharmacoKinetics (PBPK). Currently, generic product equivalents of reference-listed products dominate the topical delivery market. There is an increasing regulatory interest in understanding topical product delivery behavior under 'in use' conditions and predicting in vivo response for population variations in skin barrier function and response using in silico and in vitro findings.

Optical Characterization of Zinc Pyrithione.

Zinc pyrithione is ubiquitous in commercial products particularly antidandruff shampoos. For the efficacy of zinc pyrithione therapeutic cleansers to be assessed accurately, the distribution of particles on the scalp needs to be visualized. Currently, no technique is available which provides the chemical specificity and sensitivity required. Here, we report application of fluorescence-lifetime imaging microscopy (FLIM) for high-contrast mapping of zinc pyrithione distribution on the scalp. Characterization of the zinc pyrithione emission by using both one-photon excitation at five specific wavelengths and two-photon excitation in the range of 740-820 nm revealed its FLIM fingerprint-a characteristic short average time-weighted emission lifetime of ΤZnPT = 250 ps. Bandpass-filtering FLIM signals at ΤZnPT enabled an efficient discrimination between the zinc pyrithione and major endogenous skin species in comparison with that of the conventional reflectance confocal microscopy. Our findings provide means for in vivo high-sensitivity assaying and high-contrast imaging of zinc pyrithione in biological systems.