Preem Liis, Bock Frederik, Hinnu Mariliis, Putrinš Marta, Sagor Kadi, Tenson Tanel, Meos Andres, Østergaard Jesper, Kogermann Karin
Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark.
Pharmaceutics. 2019 Sep 19;11(9):487. doi: 10.3390/pharmaceutics11090487.
New strategies are continuously sought for the treatment of skin and wound infections due to increased problems with non-healing wounds. Electrospun nanofiber mats with antibacterial agents as drug delivery systems provide opportunities for the eradication of bacterial infections as well as wound healing. Antibacterial activities of such mats are directly linked with their drug release behavior. Traditional pharmacopoeial drug release testing settings are not always suitable for analyzing the release behavior of fiber mats intended for the local drug delivery. We tested and compared different drug release model systems for the previously characterized electrospun chloramphenicol (CAM)-loaded nanofiber (polycaprolactone (PCL)) and microfiber (PCL in combination with polyethylene oxide) mats with different drug release profiles. Drug release into buffer solution and hydrogel was investigated and drug concentration was determined using either high-performance liquid chromatography, ultraviolet-visible spectrophotometry, or ultraviolet (UV) imaging. The CAM release and its antibacterial effects in disc diffusion assay were assessed by bacterial bioreporters. All tested model systems enabled to study the drug release from electrospun mats. It was found that the release into buffer solution showed larger differences in the drug release rate between differently designed mats compared to the hydrogel release tests. The UV imaging method provided an insight into the interactions with an agarose hydrogel mimicking wound tissue, thus giving us information about early drug release from the mat. Bacterial bioreporters showed clear correlations between the drug release into gel and antibacterial activity of the electrospun CAM-loaded mats.
由于伤口愈合问题增多，人们一直在不断寻求治疗皮肤和伤口感染的新策略。含有抗菌剂作为药物递送系统的电纺纳米纤维垫为根除细菌感染以及伤口愈合提供了机会。此类垫子的抗菌活性与其药物释放行为直接相关。传统药典药物释放测试设置并不总是适合分析用于局部药物递送的纤维垫的释放行为。我们测试并比较了不同的药物释放模型系统，用于之前已表征的负载氯霉素（CAM）的电纺纳米纤维（聚己内酯（PCL））和微纤维（PCL与聚环氧乙烷组合）垫，这些垫子具有不同的药物释放曲线。研究了药物在缓冲溶液和水凝胶中的释放情况，并使用高效液相色谱法、紫外可见分光光度法或紫外（UV）成像法测定药物浓度。通过细菌生物报告器评估CAM在纸片扩散试验中的释放及其抗菌效果。所有测试的模型系统都能够研究电纺垫中的药物释放。结果发现，与水凝胶释放测试相比，在缓冲溶液中的释放显示出不同设计的垫子之间药物释放速率的差异更大。UV成像方法提供了对与模拟伤口组织的琼脂糖水凝胶相互作用的洞察，从而为我们提供了关于药物从垫子早期释放的信息。细菌生物报告器显示了药物在凝胶中的释放与负载CAM的电纺垫的抗菌活性之间的明显相关性。
