Pharmacokinetic control on the release of antimicrobial drugs from pH-responsive electrospun wound dressings.

Pharmacokinetic control on the release of antimicrobial drugs from pH-responsive electrospun wound dressings.
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pH 响应静电纺伤口敷料释放抗菌药物的药代动力学控制。

DOI:
10.1016/j.ijpharm.2022.122003
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发表时间:
2022
影响因子:
5.8
通讯作者:
S. Irusta
S. Irusta
中科院分区:
医学2区
文献类型:
--
作者:
Laura Miranda;C. Yus;Guillermo Landa;G. Mendoza;M. Arruebo;S. Irusta

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健康皮肤的酸性pH值在伤口愈合过程中会发生变化,这是由于皮肤内和皮下组织的暴露以及致病菌的潜在定植。在慢性不愈合的伤口中,pH值变化范围很广,但碱性转移的表现很常见。伤口发生后,伤口床的中性pH值是再生和重塑过程级联激活的特征。为了使药物释放调节到伤口的特定pH值,本研究开发了含有防腐剂和抗生素的具有pH响应性的载药伤口敷料,并施加不同的释放动力学,使药物释放动力学与每种伤口类型的pH条件完美匹配。我们利用pH依赖的甲基丙烯酸共聚物Eudragit®L100-55(溶解于pH > 5.5)制备了负载药物的电纺丝纳米纤维,其中含有抗菌氯己定、广谱抗生素利福平和天然抗菌百里香酚;这些药物被装载在Eudragit®S100中,Eudragit®S100在pH值为bb70时溶解,最后,在甲基丙烯酸酯共聚物Eudragit®RS100中,Eudragit®RS100与pH值无关,缓慢侵蚀并释放其所含的货物。这些高级伤口敷料的抗菌作用已被评估对甲氧西林敏感。金黄色葡萄球菌纽曼菌株表达珊瑚绿荧光蛋白(cGFP),作为革兰氏阳性菌的模型,并抗ste。大肠杆菌17菌株作为革兰氏阴性菌的模型。结果表明,这些组合产品在一个设备中集成了伤口敷料所需的特性,并具有含有活性原理的治疗作用,并且可以根据伤口的酸性或碱性状态进行选择,以进行适当的管理。
The acidic pH of healthy skin changes during wound healing due to the exposure of the inner dermal and subcutaneous tissue and due to the potential colonization of pathogenic bacteria. In chronic non-healing wounds, the pH values vary in a wide pH range but the appearance of an alkaline shift is common. After a wound is incurred, neutral pH in the wound bed is characteristic of the activation of the cascade of regenerative and remodeling processes. In order to adjust drug release to the specific pH of the wound, herein, drug-loaded wound dressings having pH-responsiveness containing antiseptics and antibiotics and exerting different release kinetics in order to have a perfect match between the drug release kinetics, and the pH conditions of each wound type, were developed. We have fabricated drug-loaded electrospun nanofibers loaded with the antiseptic chlorhexidine, with the broad-spectrum antibiotic rifampicin, and with the antimicrobial of natural origin thymol, using the pH-dependent methacrylic acid copolymer Eudragit® L100-55, which dissolves at pH > 5.5; those drugs were loaded within Eudragit® S100, which dissolves at pH > 7 and, finally, within the methacrylic ester copolymer Eudragit® RS100 which is pH independent and slowly erodes and releases its contained cargo. The antibacterial action of those advanced wound dressings has been evaluated against methicillin-sensitiveS. aureusNewman strain expressing the coral green fluorescent protein (cGFP), as a model of a Gram-positive bacteria, and againstE. coliS17 strain as a model of a Gram-negative bacteria. It was demonstrated that those combinational products integrate in one device the required characteristics for a wound dressing with the therapeutic action of a contained active principle and can be selected depending on the wound acidic or alkaline status for its appropriated management.