Peng Xueli, Yan Chenxin, Fan Nengquan, Sun Chaoguo, Zhang Suohui, Gao Yunhua
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry of Chinese Academy of Sciences, Beijing 100190, China.
Beijing CAS Microneedle Technology Ltd., Beijing 102609, China.
Polymers (Basel). 2025 May 1;17(9):1238. doi: 10.3390/polym17091238.
Port-wine stain (PWS), a progressive congenital vascular malformation characterized by ectatic dermal capillaries, demonstrates age-dependent lesion expansion and chromatic intensification, resulting in significant psychosocial comorbidity. While systemic hematoporphyrin (HP) administration remains the clinical paradigm for photodynamic therapy (PDT), its therapeutic utility is severely constrained by non-targeted biodistribution. Pharmacokinetic analyses reveal prolonged dermal retention and suboptimal lesion accumulation, predisposing 42% of patients to phototoxic reactions. To address these limitations, this work creatively suggested a local targeted drug delivery method based on soluble microneedles in response to the difficulties mentioned above. The rational design of a molecular weight (MW) HA gradient system enabled the engineering of ternary nanocomposite microneedles with enhanced biomechanical integrity (0.49 N/needle) and superior HP loading capacity, which collectively facilitated spatiotemporally controlled transdermal delivery of hematoporphyrin with complete dissolution within 30 min. The release performance, skin permeability, and storage stability of hematoporphyrin dissolving microneedles (HP-DMNs) have all been demonstrated in vitro. This study applies soluble microneedle technology to the delivery of HP in PWS for the first time. It avoids the risk of systemic exposure through precise local administration. It uses the rapid dissolution properties of microneedles to achieve high concentration and rapid release of drugs in skin lesions. This study provides a new strategy for sustained intralesional release and rapid drug delivery treatment of PWS and provides novel ideas for the development of new formulations of HP and related photosensitizers.
葡萄酒色斑（PWS）是一种以真皮毛细血管扩张为特征的进行性先天性血管畸形，表现出随年龄增长的病变扩展和颜色加深，导致严重的心理社会合并症。虽然全身给予血卟啉（HP）仍然是光动力疗法（PDT）的临床范例，但其治疗效用受到非靶向生物分布的严重限制。药代动力学分析显示，皮肤滞留时间延长且病变部位药物蓄积不理想，使42%的患者易发生光毒性反应。为了解决这些局限性，针对上述难题，本研究创新性地提出了一种基于可溶性微针的局部靶向给药方法。通过合理设计分子量（MW）HA梯度系统，构建了具有增强生物力学完整性（每根微针0.49 N）和卓越HP负载能力的三元纳米复合微针，共同促进了血卟啉在时空控制下的透皮递送，并在30分钟内完全溶解。血卟啉溶解微针（HP-DMNs）的释放性能、皮肤渗透性和储存稳定性均已在体外得到证实。本研究首次将可溶性微针技术应用于PWS中HP的递送。它通过精确的局部给药避免了全身暴露的风险。利用微针的快速溶解特性，实现了药物在皮肤病变部位的高浓度快速释放。本研究为PWS的持续病灶内释放和快速给药治疗提供了新策略，为HP及相关光敏剂新剂型的开发提供了新思路。
