一种新型溶剂挤出他克莫司洗脱缝合线,可减轻皮肤修复中的炎症和瘢痕形成

IF 4.5 3区 医学 Q1 PHARMACOLOGY & PHARMACY Journal of Drug Delivery Science and Technology Pub Date : 2024-11-02 DOI:10.1016/j.jddst.2024.106374
Azur Azapagic , Jayant Agarwal , Bruce Gale , Jill Shea , Himanshu Jayant Sant
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引用次数: 0

摘要

本研究旨在设计一种可吸收缝合线,在局部释放免疫抑制剂他克莫司(FK506),通过调节炎症来减轻瘢痕组织的形成。随着缝合线的降解,FK506 会直接释放到修复部位。聚(l-乳酸-共己内酯)(PLLA-PCL)聚合物和 0.2% wt 的 FK506 采用溶剂挤出技术共挤制成药物洗脱缝合线。对所生成缝合线的性能进行了评估,包括体外的 FK506 释放情况、体内小鼠模型的伤口闭合情况、小鼠皮肤组织学的结构和炎症标记以及缝合线和愈合的小鼠皮肤的机械强度。生成的缝合线能以≤10 纳克/天的速率持续释放 FK506。退火后,缝合线保留了 60% 的预期拉伸强度,并显示出更强的延展性。组织学检查和体内小鼠研究表明,与使用安慰剂聚(乙醇-共聚己内酯)(PGCL)缝合线处理的伤口相比,使用 FK506 洗脱 PLLA-PCL 缝合线处理的伤口表皮层变薄,整合素 β4 表达增强,角质形成细胞增多,炎症减轻,瘢痕减少,表明愈合组织有所改善。对愈合组织的机械评估表明,与安慰剂PGCL缝合线相比,药物-PLLA-PCL缝合线不会降低皮肤的机械强度。FK506洗脱PLLA-PCL缝合线通过提供靶向给药,在促进伤口愈合方面显示出良好的效果。这种创新方法可以改善伤口愈合,并提供一种简化的疤痕管理方法。为了完善生产工艺,确保缝合线的性能符合临床要求,还需要继续进行研究、优化和大规模研究。
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A novel solvent-extruded tacrolimus-eluting suture for attenuated inflammation and scarring in skin repair
This study aimed to design an absorbable suture that locally delivers the immunosuppressive agent, tacrolimus (FK506), to attenuate scar tissue formation by modulating inflammation. As the suture degrades, it releases FK506 directly into the repair site. The poly (l-lactide-co-caprolactone) (PLLA-PCL) polymer and 0.2 % wt FK506 were co-extruded using a solvent extrusion technique to generate the drug-eluting sutures. The properties of the generated sutures were assessed regarding FK506 release in vitro, wound closure in an in vivo murine model, murine skin histology for structural and inflammatory markers, and mechanical strength of both sutures and healed murine skin. The generated suture consistently released FK506 at ≤10 ng/day rates. Following annealing, the sutures retained 60 % of their anticipated tensile strength, exhibiting enhanced ductility. The histological examination and in vivo murine study indicated that wounds treated with FK506-eluting PLLA-PCL sutures produced a thinner epidermal layer, enhanced integrin β4 expression, increased keratinocyte presence, attenuated inflammation, and reduced scarring, demonstrating healed tissue improvements compared with those treated with the placebo, poly (glycolic-co-caprolactone) (PGCL), sutures. Mechanical evaluations of healed tissue indicated that drug-PLLA-PCL sutures did not reduce the mechanical strength of the skin compared to placebo PGCL sutures. The FK506-eluting PLLA-PCL sutures show promising results in advancing wound healing by offering targeted drug delivery. This innovative method can improve wound healing and provide a streamlined approach to scar management. Continued research, optimization, and broad-scale studies are needed to refine the manufacturing process and ensure that the properties of the suture meet clinical requirements.
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来源期刊
CiteScore
8.00
自引率
8.00%
发文量
879
审稿时长
94 days
期刊介绍: The Journal of Drug Delivery Science and Technology is an international journal devoted to drug delivery and pharmaceutical technology. The journal covers all innovative aspects of all pharmaceutical dosage forms and the most advanced research on controlled release, bioavailability and drug absorption, nanomedicines, gene delivery, tissue engineering, etc. Hot topics, related to manufacturing processes and quality control, are also welcomed.
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