Targeted Delivery of Zinc Pyrithione to Skin Epithelia

Abstract

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.

In Vitro Growth-Inhibitory Synergistic Effect of Zinc Pyrithione in Combination with Gentamicin against Bacterial Skin Pathogens of Livestock

“…According to the National Registration Authority for Agricultural and Veterinary Chemicals, dermal exposure of zinc pyrithione is practically non-toxic to mammals with a median lethal dose to albino rabbits > 2000 mg/kg [ 46 ]. Its permeation to the skin is very low, typically representing less than 0.05% of the initial applied dose [ 47 ]. For example, a 0.1% solution of the zinc pyrithione soap injected intracutaneously into depilated guinea pig skin at an initial dose of 0.05 mL and nine subsequent doses of 0.1 mL on alternate weekdays, did not cause any evidence of sensitization [ 48 ].…”

Male Reproductive Toxicity of Antifouling Chemicals: Insights into Oxidative Stress-Induced Infertility and Molecular Mechanisms of Zinc Pyrithione (ZPT)

“…Antifouling chemicals have been found to possess a significant toxicity towards the male reproductive system. ZPT, a complex comprising of a pair of pyrithione rings connected to the central metal ion through a bridge formed by zinc and oxygen atoms, exhibits antimicrobial properties and demonstrates a broad spectrum of antibacterial activity against various microorganisms, including bacteria, fungi, and both gram-positive and gram-negative strains [46][47][48][49]. Notably, its extremely low solubility allows for its formulation and application as a particulate material, offering distinct performance advantages [47].…”

“…ZPT, a complex comprising of a pair of pyrithione rings connected to the central metal ion through a bridge formed by zinc and oxygen atoms, exhibits antimicrobial properties and demonstrates a broad spectrum of antibacterial activity against various microorganisms, including bacteria, fungi, and both gram-positive and gram-negative strains [46][47][48][49]. Notably, its extremely low solubility allows for its formulation and application as a particulate material, offering distinct performance advantages [47]. ZPT has been widely utilized in the field of dermatology for over five decades, primarily due to its effectiveness in treating conditions such as dandruff and seborrheic dermatitis [46,49,50].…”

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

“…Malesezzia yeast have been implicated in the development, progression and recurrence of dandruff and SD [ 3 ]. The primary mode of action of ZnPT is related to its antimycotic properties against Malassezia with a minimum inhibitory concentration of 10–15 ppm [ 4 ]. The effective delivery of ZnPT from formulation to the scalp is critical for its efficacy.…”

“…Previous methods for detecting follicular ZnPT include confocal microscopy [ 10 ], autoradiography [ 11 ] and Raman microscopy [ 12 ]. Whilst these are important techniques and potentially complementary to the multimodal imaging technique described here, they have some important disadvantages [ 4 ]. Reflectance confocal microscopy suffers from the limitation of being non-specific for ZnPT, meaning debris and other ingredients deposited on the scalp may interfere with detection.…”