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负载抗癌/抗菌银(I)樟脑亚胺配合物的水凝胶敷料用于治疗恶性伤口。

Hydrogel dressings loaded with anticancer/antimicrobial Ag(I) camphorimine complexes for treatment of malignant wounds.

作者信息

Costa Joana P, Silva Diana C, Marques Fernanda, Muazeia Jeremias, Leitão Jorge H, Pinto Carlos A, Saraiva Jorge A, Serro Ana P, Carvalho M Fernanda N N

机构信息

Centro de Química Estrutural, Institute of Molecular Sciences and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Avenida António José de Almeida, n° 12, 1000-043 Lisboa, Portugal.

Centro de Química Estrutural, Institute of Molecular Sciences and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Avenida António José de Almeida, n° 12, 1000-043 Lisboa, Portugal; Egas Moniz Center for Interdisciplinary Research, Egas Moniz School of Health & Science, 2829-511 Caparica, Almada, Portugal.

出版信息

Int J Pharm. 2025 Sep 15;682:125963. doi: 10.1016/j.ijpharm.2025.125963. Epub 2025 Jul 15.

Abstract

The treatment of skin wounds caused by metastatic lesions is often difficult because not many medicines exist that simultaneously act on cancer cells and bacteria. Such difficulty delays and sometimes compromises the treatment of oncologic patients. To contribute to face that problem a set of silver camphorimine compounds with antibacterial properties were assessed for activity against cancer cells A375 and MeWo melanoma cells using the MTT assay. From them, the silver camphorimine complex 1 displayed the highest combined anticancer and antibacterial activities and therefore was incorporated in a HEMA-based hydrogel to be used in a wound dressing. The hydrogel disks loaded with complex 1 effectively reduced suspensions of E. coli, P. aeruginosa and B. contaminans from the initial 5 × 10 CFU/mL to 0 CFU/mL after 24 and 48 h of incubation. In the case of S. aureus, a reduction of more than 99 % was observed after 24 h. However, after 48 h of incubation, the hydrogel was ineffective towards S. aureus. Although presenting a non-porous structure, the hydrogel revealed to be hydrophilic and able to retain a significant water content, allowing to keep the wound moist. Additionally, it exhibited mechanical and mucoadhesive properties suitable for treatments involving repeated and frequent dressing changes. The hydrogels were loaded with complex 1 by soaking and then sterilized by high hydrostatic pressure (HHP). Biocompatibility studies demonstrated that the loaded dressings were non-irritant and hemocompatible. The sterilization procedure did not affect the integrity of the complex, nor the drug release, which occurred in a sustained way through a non-Fickian diffusion mechanism. The dressing released 618.5 mg/cm/24 h, with nearly 90 % of the release occurring within the first 8 h. Considering the exudate production rates of chronic wounds and the MIC and MBC values for complex 1 it is expected that the dressings will be effective as antibacterial and anticancer agents. In vivo studies will be needed to confirm the clinical potential of the dressings. However, the produced dressings offer a promising approach for both infection control and cancer therapy in chronic wounds.

摘要

转移性病变所致皮肤伤口的治疗往往颇具难度,因为同时作用于癌细胞和细菌的药物并不多。这种困难延误了肿瘤患者的治疗,有时甚至影响治疗效果。为解决这一问题,使用MTT法评估了一组具有抗菌特性的银樟脑亚胺化合物对癌细胞A375和MeWo黑色素瘤细胞的活性。其中,银樟脑亚胺配合物1展现出最高的抗癌和抗菌综合活性,因此被掺入基于甲基丙烯酸羟乙酯(HEMA)的水凝胶中,用于伤口敷料。负载配合物1的水凝胶圆盘在孵育24小时和48小时后,能有效将大肠杆菌、铜绿假单胞菌和污染芽孢杆菌的菌悬液从初始的5×10 CFU/mL降至0 CFU/mL。对于金黄色葡萄球菌,孵育24小时后菌量减少超过99%。然而,孵育48小时后,该水凝胶对金黄色葡萄球菌无效。尽管呈现无孔结构,但该水凝胶具有亲水性且能保留大量水分,可保持伤口湿润。此外,它还具有适合反复频繁更换敷料治疗的机械性能和粘膜粘附性能。通过浸泡将配合物1负载到水凝胶中,然后采用高静水压(HHP)进行灭菌。生物相容性研究表明,负载的敷料无刺激性且具有血液相容性。灭菌过程未影响配合物的完整性,也未影响药物释放,药物通过非菲克扩散机制持续释放。该敷料每平方厘米24小时释放618.5毫克,近90%的释放量在最初8小时内发生。考虑到慢性伤口的渗出液产生速率以及配合物1的最低抑菌浓度(MIC)和最低杀菌浓度(MBC)值,预计该敷料作为抗菌和抗癌剂将是有效的。需要进行体内研究以确认该敷料的临床潜力。然而,所制备的敷料为慢性伤口的感染控制和癌症治疗提供了一种有前景的方法。

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