Dziemidowicz Karolina, Meszarik Mark, Piovesan Jacopo, Almatroudi Mazna A, Williams Gareth R, Murdan Sudaxshina
Department of Pharmaceutics, UCL School of Pharmacy, University College London, London, United Kingdom.
Front Drug Deliv. 2024 Sep 16;4:1458009. doi: 10.3389/fddev.2024.1458009. eCollection 2024.
Fungal infections, though affecting healthcare globally, receive insufficient attention in clinical and academic settings. Invasive fungal infections, particularly caused by combat wounds, have been identified as a critical threat by the US Department of Defense. Monotherapy with traditional antifungals is often insufficient, and so combination therapies are explored to enhance treatment efficacy. However, systemic combination treatments can result in severe adverse effects, suggesting the need for localised delivery systems, such as drug-loaded electrospun patches, to administer antifungals directly to the infection site. This proof-of-concept study hypothesised that dual amorolfine and terbinafine therapy slowly releasing from electrospun patches would be an effective way of eradicating when the patch was applied directly to the fungal colony. The feasibility of creating electrospun materials loaded with amorolfine and terbinafine for combination antifungal therapy was investigated. Electrospinning was used to fabricate polycaprolactone (PCL) patches with varying drug loadings (2.5%, 5%, and 10% w/w) of amorolfine and terbinafine either individually or in combination. The incorporation of both drugs in the fibres was confirmed, with the drugs predominantly in an amorphous state. Results showed that combination therapy patches had a significantly greater and prolonged antifungal effect compared to monotherapy patches, with larger zones of inhibition and sustained efficacy over at least 7 days. This study therefore demonstrates that PCL-based electrospun patches containing amorolfine and terbinafine provide superior antifungal activity against compared to monotherapy patches. This approach could lower required drug doses, reducing adverse effects, and enhance patient compliance due to prolonged drug release, leading to more effective antifungal therapy.
真菌感染虽然在全球范围内影响着医疗保健,但在临床和学术环境中却未得到足够的重视。侵袭性真菌感染,尤其是由战伤引起的,已被美国国防部确定为一项重大威胁。传统抗真菌药物的单一疗法往往不足,因此人们探索联合疗法以提高治疗效果。然而,全身联合治疗可能会导致严重的不良反应,这表明需要局部给药系统,如载药电纺贴片,将抗真菌药物直接输送到感染部位。这项概念验证研究假设,当贴片直接应用于真菌菌落时,从电纺贴片中缓慢释放的阿莫罗芬和特比萘芬联合疗法将是根除真菌的有效方法。研究了制备载有阿莫罗芬和特比萘芬的电纺材料用于联合抗真菌治疗的可行性。采用静电纺丝法制备了聚己内酯(PCL)贴片,分别或联合载有不同药物负载量(2.5%、5%和10% w/w)的阿莫罗芬和特比萘芬。证实了两种药物均掺入纤维中,且药物主要处于无定形状态。结果表明,与单一疗法贴片相比,联合疗法贴片具有显著更强且更持久的抗真菌作用,抑菌圈更大且至少7天内疗效持续。因此,本研究表明,与单一疗法贴片相比,含有阿莫罗芬和特比萘芬的基于PCL的电纺贴片对真菌具有更强的抗真菌活性。这种方法可以降低所需的药物剂量,减少不良反应,并由于药物的持续释放而提高患者的依从性,从而实现更有效的抗真菌治疗。