多策略结合：一种新型交联水凝胶形成的壳聚糖基微针化学包裹贴片，载有5-氟尿嘧啶脂质体，用于慢性创伤癌症治疗

Multiple strategies approach: A novel crosslinked hydrogel forming chitosan-based microneedles chemowrap patch loaded with 5-fluorouracil liposomes for chronic wound cancer treatment

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

影响因子:8.5

分区:生物学2区 Top / 生化与分子生物学2区应用化学2区高分子科学2区

发表日期:2024 Nov

作者: Phuvamin Suriyaamporn, Koranat Dechsri, Thapakorn Charoenying, Tanasait Ngawhirunpat, Theerasak Rojanarata, Prasopchai Patrojanasophon, Praneet Opanasopit, Boonnada Pamornpathomkul

DOI: 10.1016/j.ijbiomac.2024.134973

摘要

未治疗或管理不善的慢性创伤可能发展为皮肤癌。局部应用的5-氟尿嘧啶（5-FU），一种非特异性的细胞毒性药物，可能引起多种副作用。其高极性还导致细胞膜亲和性和生物利用度低。水凝胶由于其封闭效应被广泛用于慢性创伤的治疗，结合PEG化脂质体（LPs）开发，以增强药物与皮肤的亲和性。本研究旨在开发一种新型交联水凝胶形成的壳聚糖基微针（HFM）化学包裹贴片，含有5-FU PEG化脂质体，以提高5-FU在前癌和癌变皮肤病变中的疗效。结果显示，载有5-FU PEG化脂质体的HFM化学包裹贴片具有理想的物理和机械性能，具有完全穿透能力。此外，体内皮肤渗透研究显示，该贴片在穿透率（42.06±11.82%）和皮肤沉积（75.90±1.13%）方面优于其他处理方式，在体内（第7天愈合率47.00±5.77%）和NHF细胞中的体外效果（48小时92.79±7.15%）也表现出优异的完全愈合效果。更重要的是，载有5-FU PEG化脂质体的HFM化学包裹贴片表现出高效的抗癌活性，同时对正常细胞安全。结果还显示，该配方的5-FU PEG化脂质体载体贴片能诱导比纯5-FU溶液更高的凋亡率。综上所述，该新型药物递送系统为治疗前癌和癌变皮肤病变提供了有前景的方案。

Abstract

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.