多种策略方法：一种新型的交联水凝胶形成壳聚糖的微针化学片，用5-氟尿嘧啶脂质体负载用于慢性伤口癌治疗
Multiple strategies approach: A novel crosslinked hydrogel forming chitosan-based microneedles chemowrap patch loaded with 5-fluorouracil liposomes for chronic wound cancer treatment
影响因子:8.50000
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
摘要
未经治疗或管理不良的慢性伤口可以发展为皮肤癌。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。它的高极性还导致低细胞膜亲和力和生物利用度。用于闭塞作用的水凝胶是处理慢性伤口与叶状性脂质体（LPS）相结合的一个平台，用于增加药物皮肤亲和力。这项研究旨在开发一种新型的水凝胶形成壳聚糖的微针（HFM）ChemoWrap贴片，其中含有5-FU PEGYPER LPS，从而提高了5-FU效率，可用于治疗前和致癌性皮肤病变。结果表明，5-FU-PEGYPY LPS负载的HFM ChemoWrap贴片具有完全穿透能力的理想物理和机械特性。 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）。此外，5-FU-PEGYPY LPS负载的HFM ChemoWrap贴片表现出有效的抗癌活性，同时保持正常细胞的安全性。结果还表明，发达的5-FU-PEGYPARED LPS LPS HFM CHEMOWRAP贴片的配方可能会增强凋亡，高于5-FU溶液的细胞凋亡。因此，5-FU的pegyated LPS负载的HFM ChemoWrap贴片代表了一种有前途的药物输送方法，用于治疗癌前和致癌性皮肤病变。
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.