Key Laboratory of UV-Emitting Materials and Technology, Northeast Normal University, Ministry of Education, Changchun, Jilin 130024, China; School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
Key Laboratory of UV-Emitting Materials and Technology, Northeast Normal University, Ministry of Education, Changchun, Jilin 130024, China.
Mater Sci Eng C Mater Biol Appl. 2019 Nov;104:109745. doi: 10.1016/j.msec.2019.109745. Epub 2019 Jul 3.
Chronic wounds are of high incidence, difficult to heal, and can cause serious consequences if not properly treated. Doxycycline (DCH) is a broad-spectrum antibiotic and matrix metalloproteinases inhibitor, which has prominent efficacy for chronic wound treatment. Topical DCH treatment is the common administration route for chronic wounds in clinic but may result in low therapeutic efficacy and cause skin irritation at high DCH concentration, since it is difficult to control local drug concentration in the wounds and maintain the effective DCH concentration for a long time. In this study, we prepared DCH-encapsulated polylactide (DCH/PLA) nanofibers by a simple electrospinning method. Imaging studies showed that smooth and continuous DCH/PLA nanofibers with homogeneous DCH distribution were obtained at varied DCH loading content in the range of 5-30%. Mechanical property, water vapour permeability and absorbency of these nanofibers could meet the requirement as wound dressings. By adjusting DCH loading content, the wettability of the nanofibers could be transferred from hydrophobic to hydrophilic, and the release rate of DCH could be controlled in a sustained manner from three days to two weeks. Results of cytotoxicity and antibacterial test indicated that DCH/PLA nanofibers showed good cytocompatibility to L929 mouse fibroblast cells and exhibited positive antibacterial activity against Escherichia coli, suggesting its ability to treat/prevent infectious wounds. For full-thickness wound treatment of diabetic rats, DCH/PLA nanofiber mats can speed up wound healing to a higher extent than topical DCH treatment, due to the sustained release of DCH with less side effects. Our results indicate that DCH/PLA nanofiber mats hold great potential as wound dressings for chronic wound treatment.
慢性创面发病率高，愈合困难，如果治疗不当，可能会导致严重后果。多西环素（DCH）是一种广谱抗生素和基质金属蛋白酶抑制剂，对慢性创面治疗具有显著疗效。局部应用 DCH 是临床治疗慢性创面的常用给药途径，但由于难以控制创面局部药物浓度，且在高 DCH 浓度下会引起皮肤刺激，因此疗效较低。在本研究中，我们通过简单的静电纺丝法制备了 DCH 包封的聚乳酸（DCH/PLA）纳米纤维。成像研究表明，在 5-30%的不同 DCH 载药量范围内，可获得均匀分布 DCH 的光滑连续 DCH/PLA 纳米纤维。这些纳米纤维的机械性能、水蒸气透过率和吸湿性均能满足创面敷料的要求。通过调节 DCH 载药量，纳米纤维的润湿性可以从疏水转变为亲水，并且 DCH 的释放速率可以从 3 天到 2 周持续控制。细胞毒性和抗菌试验结果表明，DCH/PLA 纳米纤维对 L929 小鼠成纤维细胞具有良好的细胞相容性，并对大肠杆菌表现出积极的抗菌活性，表明其具有治疗/预防感染性创面的能力。对于糖尿病大鼠全层创面治疗，DCH/PLA 纳米纤维垫可在更大程度上加速创面愈合，这是由于 DCH 的持续释放，副作用较少。我们的研究结果表明，DCH/PLA 纳米纤维垫具有作为慢性创面治疗用创面敷料的巨大潜力。
