Microneedle-assisted transdermal delivery of perfluorotripropylamine-based oxygenated emulsion gel loaded with 5-aminolevulinic acid for enhanced photodynamic therapy of cutaneous squamous cell carcinoma

作者：Jialiang Zhang, Qiang Feng, Jianbin Xiao, Jinyu Zhang, Lin Jiao, Jianmin Wang · 发表于：European Journal of Pharmaceutical Sciences · 年份：2023 · DOI：10.1016/j.ejps.2023.106493 · 被引用次数：10 · 研究领域：Photodynamic Therapy Research Studies、Nanoplatforms for cancer theranostics、Advancements in Transdermal Drug Delivery

Topical photodynamic therapy (TPDT) is a clinical treatment for cutaneous squamous cell carcinoma (CSCC). However, the therapeutic efficacy of TPDT for CSCC is significantly weakened by hypoxia, which is caused by the oxygen-poor environment of the skin and CSCC and by the high oxygen consumption of TPDT itself. To overcome these problems, we developed a topically applied perfluorotripropylamine-based oxygenated emulsion gel loaded with the photosensitizer 5-ALA (5-ALA-PBOEG) by a simple ultrasound-assisted emulsion method. With the aid of the microneedle roller, 5-ALA-PBOEG dramatically increased the accumulation of 5-ALA in the epidermis and the dermis, as well as throughout the dermis; a total of 67.6% ± 9.97% of the applied dose penetrated into and through the dermis, which is 19.1±3.2-fold that of the 5-ALA-PBOEG without microneedle treatment group, and 16.9±0.3-fold that of the aminolevulinic acid hydrochloride topical powder treatment group (p<0.001). Meanwhile, PBOEG enhanced the singlet oxygen yield of 5-ALA-induced protoporphyrin IX. The results of in vivo antitumor activity in human epidermoid carcinoma (A431) bearing mice showed that by increasing the oxygen content in tumor tissues, the developed 5-ALA-PBOEG plus microneedle treatment and laser irradiation showed better tumor growth inhibition than the respective control formulations. In addition, the results of safety studies, including the multiple-dose skin irritation study, allergy tests, and skin H&E stainin...