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氧化纤维素微针贴片联合血管栓塞和马来酸噻吗洛尔局部递送治疗血管瘤。

Oxidized cellulose microneedle patch combined with vascular embolization and local delivery of timolol maleate for hemangiomas.

机构信息

Department of Interventional Hemangioma, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510600, China.

Department of Interventional Hemangioma, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510600, China.

出版信息

Colloids Surf B Biointerfaces. 2024 Dec;244:114174. doi: 10.1016/j.colsurfb.2024.114174. Epub 2024 Aug 24.

DOI:10.1016/j.colsurfb.2024.114174
PMID:39197327
Abstract

Hemangiomas are superficial tumors characterized by dense vascular structures that often affect the patient's aesthetic appearance due to the obvious red appearance on the skin. Current treatments, especially timolol maleate in the form of eye drops and hydrogels, suffer from low transdermal drug delivery rates, resulting in prolonged treatment time. To address this challenge, our study introduced a soluble microneedle patch with dextran as the main material to form microcatheters for sustained delivery of timolol maleate. In addition, we proposed a vascular embolization strategy to disrupt the blood supply in hemangiomas. Oxidized cellulose (C-cellulose) was selected for its excellent hemostatic properties. We incorporated C-cellulose into dextran microneedles to facilitate thrombosis in the vascular-rich areas of hemangiomas. The innovative microneedle patch we developed can penetrate the skin to a depth of 430 μm and dissolve rapidly within 3 minutes, ensuring direct drug delivery to the subcutaneous layer. Notably, the treated skin area regained its original appearance within two hours after treatment. In addition to excellent skin permeability and rapid dissolution, these patches significantly promoted apoptosis and inhibited cell migration in mouse hemangioendothelioma EOMA cells. Our results demonstrate that this approach not only achieves significant tumor inhibition in a mouse hemangioma model, but also represents a more effective, convenient, and non-invasive treatment option. Therefore, dextran/C-cellulose/timolol maleate microneedle patch (MNs/Timolol) has broad clinical application prospects in the treatment of hemangiomas, minimizing the risk of additional damage and improving treatment efficacy.

摘要

血管瘤是一种表面肿瘤,其特征是密集的血管结构,由于皮肤表面明显的红色外观,往往会影响患者的美观。目前的治疗方法,特别是马来酸噻吗洛尔滴眼液和水凝胶的形式,存在经皮药物递送率低的问题,导致治疗时间延长。针对这一挑战,我们的研究引入了一种以葡聚糖为主要材料的可溶性微针贴片,形成微导管,以持续递送马来酸噻吗洛尔。此外,我们提出了一种血管栓塞策略,以破坏血管瘤的血液供应。氧化纤维素(C-纤维素)因其出色的止血性能而被选中。我们将 C-纤维素纳入葡聚糖微针中,以促进血管瘤富含血管区域的血栓形成。我们开发的创新微针贴片可以穿透皮肤达 430μm 深度,并在 3 分钟内迅速溶解,确保药物直接递送至皮下层。值得注意的是,治疗后的皮肤区域在治疗后两小时内恢复到原来的外观。除了出色的皮肤渗透性和快速溶解外,这些贴片还显著促进了小鼠血管内皮细胞瘤 EOMA 细胞的凋亡和抑制细胞迁移。我们的结果表明,这种方法不仅在小鼠血管瘤模型中实现了显著的肿瘤抑制,而且还提供了一种更有效、方便和非侵入性的治疗选择。因此,葡聚糖/C-纤维素/马来酸噻吗洛尔微针贴片(MNs/Timolol)在治疗血管瘤方面具有广阔的临床应用前景,可以最大限度地减少额外损伤并提高治疗效果。

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Oxidized cellulose microneedle patch combined with vascular embolization and local delivery of timolol maleate for hemangiomas.氧化纤维素微针贴片联合血管栓塞和马来酸噻吗洛尔局部递送治疗血管瘤。
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