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首页> 美国卫生研究院文献>Pharmaceutics >Methylene Blue-Loaded Dissolving Microneedles: Potential Use in Photodynamic Antimicrobial Chemotherapy of Infected Wounds
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Methylene Blue-Loaded Dissolving Microneedles: Potential Use in Photodynamic Antimicrobial Chemotherapy of Infected Wounds

机译：亚甲蓝负载的溶解性微针：感染伤口的光动力抗菌化学疗法中的潜在用途。

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Photodynamic therapy involves delivery of a photosensitising drug that is activated by light of a specific wavelength, resulting in generation of highly reactive radicals. This activated species can cause destruction of targeted cells. Application of this process for treatment of microbial infections has been termed “photodynamic antimicrobial chemotherapy” (PACT). In the treatment of chronic wounds, the delivery of photosensitising agents is often impeded by the presence of a thick hyperkeratoticecrotic tissue layer, reducing their therapeutic efficacy. Microneedles (MNs) are an emerging drug delivery technology that have been demonstrated to successfully penetrate the outer layers of the skin, whilst minimising damage to skin barrier function. Delivering photosensitising drugs using this platform has been demonstrated to have several advantages over conventional photodynamic therapy, such as, painless application, reduced erythema, enhanced cosmetic results and improved intradermal delivery. The aim of this study was to physically characterise dissolving MNs loaded with the photosensitising agent, methylene blue and assess their photodynamic antimicrobial activity. Dissolving MNs were fabricated from aqueous blends of Gantrez® AN-139 co-polymer containing varying loadings of methylene blue. A height reduction of 29.8% was observed for MNs prepared from blends containing 0.5% w/w methylene blue following application of a total force of 70.56 N/array. A previously validated insertion test was used to assess the effect of drug loading on MN insertion into a wound model. Staphylococcus aureus, Escherichia coli and Candida albicans biofilms were incubated with various methylene blue concentrations within the range delivered by MNs in vitro (0.1–2.5 mg/mL) and either irradiated at 635 nm using a Paterson Lamp or subjected to a dark period. Microbial susceptibility to PACT was determined by assessing the total viable count. Kill rates of >96%, were achieved for S. aureus and >99% for E. coli and C. albicans with the combination of PACT and methylene blue concentrations between 0.1 and 2.5 mg/mL. A reduction in the colony count was also observed when incorporating the photosensitiser without irradiation, this reduction was more notable in S. aureus and E. coli strains than in C. albicans.
机译：光动力疗法涉及递送光敏药物，该光敏药物被特定波长的光激活，导致产生高反应性自由基。这种活化的物质可以引起靶细胞的破坏。该方法在治疗微生物感染中的应用被称为“光动力抗微生物化学疗法”（PACT）。在慢性伤口的治疗中，光敏剂的递送常常由于厚角化过度/坏死组织层的存在而受到阻碍，从而降低了它们的治疗功效。微针（MNs）是一种新兴的药物输送技术，已被证明能够成功穿透皮肤的外层，同时最大程度地减少对皮肤屏障功能的损害。与传统的光动力疗法相比，已证明使用该平台递送光敏药物具有许多优势，例如无痛应用，减少红斑，增强美容效果和改善皮内递送。这项研究的目的是物理表征负载有光敏剂，亚甲基蓝的可溶性MN，并评估其光动力抗菌活性。溶解性MNs由含有不同负载量的亚甲基蓝的Gantrez AN-139共聚物的水性共混物制成。施加70.56 N /阵列的总力后，由含0.5％w / w亚甲基蓝的共混物制备的MN的高度降低了29.8％。先前已验证的插入测试用于评估药物负载对MN插入伤口模型的影响。将金黄色葡萄球菌，大肠杆菌和白色念珠菌生物膜与各种MNs浓度范围内的亚甲蓝在体外孵育（0.1–2.5 mg / mL），并用Paterson灯在635 nm处照射或置于暗处。通过评估总存活数来确定对PACT的微生物敏感性。金黄色葡萄球菌的杀灭率> 96％，大肠杆菌和白色念珠菌的杀灭率达到> 99％，PACT和亚甲基蓝浓度的组合在0.1和2.5 mg / mL之间。当掺入未经照射的光敏剂时，也观察到菌落数的减少，这种减少在金黄色葡萄球菌和大肠杆菌菌株中比在白色念珠菌中更明显。

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