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Multi-Modal Imaging to Assess the Follicular Delivery of Zinc Pyrithione
Sean E Mangion1,2,3, Lydia Sandiford1,2, Yousuf Mohammed4
1Therapeutics Research Centre, UniSA-Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, USA.
Abstract:
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.
Insights
This study used advanced microscopy to track zinc pyrithione (ZnPT) antifungal particles in skin follicles. FLIM imaging revealed ZnPT
Area of Science:
- Dermatology and Pharmaceutical Sciences
- Microscopy and Imaging Technologies
- Biophysical Chemistry
Background:
- Zinc pyrithione (ZnPT) is a common antifungal agent delivered via microparticles into hair follicles.
- ZnPT dissociates into a bioactive monomeric form effective against yeast and microorganisms.
- Understanding ZnPT formulation and delivery is crucial for optimizing antifungal treatments.
Purpose of the Study:
- To characterize ZnPT formulations using multiphoton microscopy (MPM) and fluorescence lifetime imaging microscopy (FLIM).
- To map the delivery and dissolution of ZnPT particles within human hair follicles.
- To evaluate the impact of application techniques (massage vs. no-massage) on ZnPT delivery.
Main Methods:
- Utilized multiphoton microscopy (MPM) and fluorescence lifetime imaging microscopy (FLIM) for imaging.
- Employed Zinpyr-1, a fluorescent probe, to assess zinc dissolution in real-time.
- Applied ZnPT formulations to human skin simulating massage and no-massage conditions.
Main Results:
- FLIM demonstrated superior sensitivity and selectivity for detecting ZnPT particles compared to MPM.
- Larger ZnPT particles (7.2 µm) in aqueous suspension were traceable up to 500 µm deep in follicles.
- Finer ZnPT particles (1.0-3.3 µm) in formulations showed rapid dissolution, with reduced particle signals and increased Zinpyr-1 intensity at 24 hours.
Conclusions:
- MPM-FLIM multimodal imaging is an effective tool for assessing ZnPT delivery and dissolution in skin.
- Particle size and formulation significantly influence ZnPT's dissolution rate and distribution in follicles.
- This imaging approach provides valuable insights for developing improved topical antifungal delivery systems.
