未经治疗或管理不善的慢性伤口可能会发展为皮肤癌。局部应用 5-氟尿嘧啶 (5-FU)（一种非特异性细胞抑制剂）可能会引起各种副作用。其高极性还导致细胞膜亲和力和生物利用度低。水凝胶因其闭塞作用而成为治疗慢性伤口的一种平台，与聚乙二醇化脂质体 (LP) 相结合，旨在增加药物与皮肤的亲和力。本研究旨在开发一种新型水凝胶形成的基于壳聚糖的微针 (HFM) 化疗贴片，含有 5-FU 聚乙二醇化 LP，提高 5-FU 对致癌前和致癌皮肤病变的效率。结果表明，负载 5-FU-PEG 化 LPs 的 HFM 化学包裹贴剂表现出理想的物理和机械特性，具有完全渗透能力。此外，体内皮肤渗透研究表明，与其他治疗方法相比，5-FU 渗透皮肤的百分比 (42.06±11.82%) 和皮肤沉积 (75.90±1.13%) 最高，并且体内伤口完全愈合的百分比更高（第7天伤口愈合为47.00±5.77%）和NHF细胞（48小时为92.79±7.15%）。此外，装载 5-FU-聚乙二醇化 LP 的 HFM 化疗贴片表现出有效的抗癌活性，同时保持对正常细胞的安全性。结果还表明，所开发的负载 5-FU-聚乙二醇化 LPs 的 HFM 化疗贴剂的配方可以比 5-FU 溶液更高地增强细胞凋亡。因此，装载 5-FU 聚乙二醇化 LPs 的 HFM 化疗贴剂代表了一种有前景的药物递送方法，用于治疗致癌前和致癌性皮肤病变。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Untreated or poorly managed chronic wounds can progress to skin cancer. Topically applied 5-fluorouracil (5-FU), a nonspecific cytostatic agent, can cause various side effects. Its high polarity also results in low cell membrane affinity and bioavailability. Hydrogel, used for its occlusive effect, is one platform for treating chronic wounds combined with PEGylated liposomes (LPs), developed to increase drug-skin affinity. This research aimed to develop a novel hydrogel forming chitosan-based microneedles (HFM) chemowrap patch containing 5-FU PEGylated LPs, improving 5-FU efficiency for pre-carcinogenic and carcinogenic skin lesions. The results indicated that the 5-FU-PEGylated LPs-loaded HFM chemowrap patch exhibited desirable physical and mechanical characteristics with complete penetration ability. Furthermore, in vivo skin permeation studies demonstrated the highest percentage of 5-FU permeated the skin (42.06 ± 11.82 %) and skin deposition (75.90 ± 1.13 %) compared to the other treatments, with demonstrated superior percentages of complete wound healing in in vivo (47.00 ± 5.77 % wound healing at day 7) and in NHF cells (92.79 ± 7.15 % at 48 h). Furthermore, 5-FU-PEGylated LPs-loaded HFM chemowrap patches exhibit efficient anticancer activity while maintaining safety for normal cells. The results also show that the developed formulation of a 5-FU-PEGylated LPs-loaded HFM chemowrap patch could enhance apoptosis higher than that of the 5-FU solution. Consequently, 5-FU PEGylated LPs-loaded HFM chemowrap patch represented a promising drug delivery approach for treating pre-carcinogenic and carcinogenic skin lesions.Copyright © 2024 Elsevier B.V. All rights reserved.