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明胶水凝胶中用于抗菌伤口愈合的疏水药物递送一步法物理和化学双重强化

One-Step Physical and Chemical Dual-Reinforcement with Hydrophobic Drug Delivery in Gelatin Hydrogels for Antibacterial Wound Healing.

作者信息

An Di, Wang Zhengkai, Ning Yishuo, Yue Yuxing, Xuan Han, Hu Yongjin, Yang Mingdi, Zhou Haiou, Liu Qianqian, Wang Xianbiao, Wang Ping, Zhu Zhiyuan, Rao Jingyi, Zhang Jingyan

机构信息

Anhui Advanced Building Materials International Joint Research Center, School of Materials and Chemical Engineering, Anhui Jianzhu University, Hefei, Anhui 230022, P. R. China.

Hubei Key Laboratory of Material Chemistry and Service Failure, Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P. R. China.

出版信息

ACS Omega. 2024 Jul 29;9(32):34413-34427. doi: 10.1021/acsomega.4c01963. eCollection 2024 Aug 13.

DOI:10.1021/acsomega.4c01963
PMID:39157075
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11325409/
Abstract

Gelatin-based bioadhesives, especially methacrylated gelatin (GelMA), have emerged as superior alternatives to sutureless wound closure. Nowadays, their mechanical improvement and therapeutic delivery, particularly for hydrophobic antibiotics, have received ever-increasing interest. Herein, a reinforced gelatin-based hydrogel with a hydrophobic drug delivery property for skin wound treatment was reported. First, photosensitive monomers of '-(2-nitrobenzyl)--acryloyl glycinamide (NAGA) were grafted onto GelMA Michael addition, namely, GelMA-NAGA. Second, gelation of the GelMA-NAGA solution was accomplished in a few seconds under one step of ultraviolet (UV) light irradiation. Multiple effects were realized simultaneously, including chemical cross-linking initiated by lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), physical cross-linking of uncaged dual hydrogen bonding, and hydrophobic drug release along with group disintegration. The mechanical properties of the dual-reinforcement hydrogels were verified to be superior to those only with a chemical or physical single-cross-linked network. The hydrophobic anticancer doxorubicin (DOX) and antibiotic rifampicin (Rif) were successfully charged into the hydrogels, separately. The antimicrobial tests confirmed the antibacterial activity of the hydrogels against Gram-negative () and Gram-positive () bacteria. The wound-healing assessment in mice further assured their drug release and efficacy. Therefore, this NAGA-modified GelMA hydrogel has potential as a material in skin wound dressing with a hydrophobic antibiotic on-demand delivery.

摘要

基于明胶的生物粘合剂,尤其是甲基丙烯酸化明胶(GelMA),已成为无缝合伤口闭合的优质替代品。如今,它们的机械性能改善和治疗药物递送,特别是对于疏水性抗生素,受到了越来越多的关注。在此,报道了一种具有疏水性药物递送特性的用于皮肤伤口治疗的增强型明胶基水凝胶。首先,通过迈克尔加成反应将“-(2-硝基苄基)--丙烯酰甘氨酰胺(NAGA)的光敏单体接枝到GelMA上,即GelMA-NAGA。其次,GelMA-NAGA溶液在一步紫外(UV)光照射下几秒钟内即可完成凝胶化。同时实现了多种效果,包括由苯基-2,4,6-三甲基苯甲酰基次膦酸锂(LAP)引发的化学交联、未封闭的双氢键的物理交联以及随着基团分解的疏水性药物释放。经证实,双增强水凝胶的机械性能优于仅具有化学或物理单交联网络的水凝胶。疏水性抗癌药物阿霉素(DOX)和抗生素利福平(Rif)分别成功负载到水凝胶中。抗菌测试证实了水凝胶对革兰氏阴性()和革兰氏阳性()细菌的抗菌活性。小鼠伤口愈合评估进一步证实了它们的药物释放和疗效。因此,这种NAGA修饰的GelMA水凝胶有潜力作为一种具有按需递送疏水性抗生素的皮肤伤口敷料材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2746/11325409/4500981b23ef/ao4c01963_0008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2746/11325409/e833468611ab/ao4c01963_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2746/11325409/bef09afeabf4/ao4c01963_0004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2746/11325409/83b9e5a3ff56/ao4c01963_0006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2746/11325409/4500981b23ef/ao4c01963_0008.jpg

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