Mangion Sean E, Sandiford Lydia, Mohammed Yousuf, Roberts Michael S, Holmes Amy M
Therapeutics Research Centre, UniSA-Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, USA.
Basil Hetzel Institute for Translational Health Research, Woodville South, SA 5011, Australia.
Pharmaceutics. 2022 May 17;14(5):1076. doi: 10.3390/pharmaceutics14051076.
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.
吡啶硫酮锌（ZnPT）是一种广泛使用的抗真菌剂，通常以微粒悬浮液的形式应用，以促进其进入毛囊，在毛囊中它会解离成具有生物活性的可溶性单体形式，对酵母和其他微生物起作用。在本研究中，我们使用多光子显微镜（MPM）和荧光寿命成像显微镜（FLIM）来表征ZnPT制剂，并绘制颗粒在人体皮肤毛囊中的递送情况。为了模拟实际情况，采用按摩或不按摩技术应用ZnPT，同时使用锌不稳定荧光探针Zinpyr-1评估其溶解情况。使用MPM和FLIM均可在一系列洗发水制剂中检测到ZnPT颗粒，不过FLIM是检测的最佳方法，因为它能够进行光谱和寿命鉴别，从而提高选择性和灵敏度。在水悬浮液中，在毛囊中可检测到直径7.2 µm的ZnPT颗粒，深度可达500 µm。制剂中的ZnPT颗粒更细（1.0 - 3.3 µm），导致其在皮肤表面和毛囊内迅速溶解，这在24小时时颗粒信号降低但毛囊和表面上皮中的Zinpyr-1强度增强得到证明。本研究展示了MPM - FLIM多模态成像如何可作为评估ZnPT向皮肤递送及其后续溶解的有用工具。
