Microemulsions Improve Topical Protoporphyrin IX (PpIX) Delivery for Photodynamic Therapy of Skin Cancer

Abstract We report here microemulsions (MEs) for topical delivery of protoporphyrin IX (PpIX) for Photodynamic Therapy (PDT) of skin cancers. Selected MEs consisting of Oil/Water (O/W) bicontinuous (BC) and Water/Oil (W/O) preparations were characterized as to pH, nanometric size, zeta potential, drug content, and viscosity. Sustained in vitro PpIX release was achieved from MEs 2A (O/W), 10B (BC) and 16B (W/O) through an artificial membrane for up to 24 h, characterizing MEs as drug delivery systems. None of these MEs showed permeation through the skin, demonstrating the required topical effect. After 4 h, in vitro retention of PpIX in the stratum corneum (SC) was higher from both ME 10B and control (PpIX at 60 µg/mL in PEG 300). However, in the Epidermis + Dermis ([Ep + D]), retention from ME 10B and ME 16B was ~40 times higher compared to control. Confocal Laser Scanning Microscopy (CLSM) showed higher fluorescence intensity in the SC for both control and ME 10B, whereas ME 10B fluorescence was higher in [Ep+D]. The results indicate that ME 10B is suitable for PpIX encapsulation, showing good characteristics and a localized effect for a potential delivery system for PDT-associated treatments of skin cancers.

摘要 本研究报道了可用于皮肤癌光动力疗法（Photodynamic Therapy，PDT）中原卟啉IX（protoporphyrin IX，PpIX）局部递送的微乳（microemulsions，MEs）体系。本研究对经筛选的水包油（O/W）、双连续（BC）及油包水（W/O）型微乳制剂的pH值、纳米粒径、zeta电位（zeta potential）、药物含量及黏度进行了表征。结果显示，微乳2A（O/W型）、10B（双连续型）及16B（W/O型）可通过人工膜实现长达24小时的PpIX持续体外释放，证实上述微乳可作为药物递送系统。上述三类微乳均未出现经皮渗透现象，符合局部给药的预期效果。孵育4小时后，微乳10B组与对照组（将PpIX以60 μg/mL浓度溶于聚乙二醇300（PEG 300）中）的PpIX在角质层（stratum corneum，SC）中的体外滞留量均较高；但在表皮+真皮（[Ep+D]）区域，微乳10B与16B组的PpIX滞留量较对照组高约40倍。共聚焦激光扫描显微镜（Confocal Laser Scanning Microscopy，CLSM）观测结果显示，对照组与微乳10B组的角质层荧光强度均较高，而微乳10B组在表皮+真皮区域的荧光强度更高。本研究结果表明，微乳10B具备良好的PpIX包载性能，各项表征指标优良，且可实现局部递送效果，有望成为皮肤癌光动力疗法相关治疗的潜在药物递送系统。