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Desferrioxamine Enhances 5-Aminolaevulinic Acid- Induced Protoporphyrin IX Accumulation and Therapeutic Efficacy for Hypertrophic Scar
Journal of Pharmaceutical Sciences Pub Date : 2023-01-20 , DOI: 10.1016/j.xphs.2023.01.015
Yiman Chen 1 , Huihui Deng 1 , Liya Yang 1 , Ling Guo 2 , Min Feng 1
Affiliation  

Hypertrophic scar is a common problem after skin burns or trauma which brings physical, psychological, and cosmetic problems to patients. Photodynamic therapy with 5-aminolevulinic acid (5-ALA) is a promising therapy for hypertrophic scar. However, clinical applications of 5-ALA are limited because of the low permeability of 5-ALA in the skin stratum corneum and the rapid binding of protoporphyrin IX (PpIX) with iron ions, which lead to insufficient PpIX production in target tissues. Herein, a mixture of 5-ALA and DFO (deferoxamine, a special iron chelator) was applied for the treatment of hypertrophic scar. 5-ALA/DFO could efficiently block the biotransformation of PpIX to heme, thus realizing a significant accumulation of photosensitizer. In addition, injection locally into the lesion was applied, which combined with enhanced photodynamic therapy to destroy hypertrophic scar fibroblasts. In vitro experiments showed that 5-ALA/DFO could increase more ROS generation by increasing the accumulation of PpIX, resulting in the apoptosis of hypertrophic scar fibroblasts. Furthermore, 5-ALA/DFO inhibited the proliferation and migration of hypertrophic scar fibroblasts. In vivo study showed that 5-ALA/DFO could effectively inhibit the formation of proliferative scar. Therefore, 5-ALA/DFO has the potential to enhance the photodynamic therapy of 5-ALA and provides a new treatment strategy for hypertrophic scar.



中文翻译:

去铁胺增强 5-氨基乙酰丙酸诱导的原卟啉 IX 积累和治疗增生性瘢痕的疗效

增生性疤痕是皮肤烧伤或外伤后常见的问题,给患者带来身体、心理和美容方面的问题。5-氨基乙酰丙酸 (5-ALA) 的光动力疗法是治疗增生性疤痕的一种很有前途的疗法。然而,由于5-ALA在皮肤角质层的渗透性低,原卟啉IX (PpIX)与铁离子快速结合,导致靶组织PpIX生成不足,5-ALA的临床应用受到限制。在此,应用 5-ALA 和 DFO(去铁胺,一种特殊的铁螯合剂)的混合物来治疗增生性瘢痕。5-ALA/DFO 可有效阻断 PpIX 向血红素的生物转化,从而实现光敏剂。此外,局部注射到病灶处,结合增强的光动力疗法来破坏增生性瘢痕成纤维细胞。体外实验表明,5-ALA/DFO 可通过增加 PpIX 的积累来增加更多 ROS 的产生,从而导致增生性瘢痕成纤维细胞凋亡。此外,5-ALA/DFO 抑制增生性瘢痕成纤维细胞的增殖和迁移。体内研究表明,5-ALA/DFO能有效抑制增生性瘢痕的形成。因此,5-ALA/DFO具有增强5-ALA光动力疗法的潜力,为增生性瘢痕提供了一种新的治疗策略。

更新日期:2023-01-20
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