Amphotericin-B and vancomycin-loaded chitosan nanofiber for antifungal and antibacterial application

In the present study, a mucoadhesive non-woven fiber mat (d= 116 nm) was fabricated by the electrospinning method using chitosan (80% Wt), polyethylene oxide (10% Wt), cysteine (4% Wt) and drugs (6% Wt), respectively. In addition, a comparative study was conducted to define effect of drugs and mucoadhesive agent on the nanofiber formation. FTIR, SEM, DSC and DMA were used to investigate the chemical and physical properties of the nanofibers. In vitro release of the drugs was assessed over a 48-hour period by the total immersion method. Release data were fitted to kinetic models, including the zero-order, first-order, Higuchi matrix, and Hixson-Crowell. Zone inhibition investigations were used to describe the inhibition content of vancomycin and amphotericin B loaded in the mats. The SEM images displayed a slight decrease in the fiber diameter with adding drugs and mucoadhesive agents. FTIR spectra confirmed that any undesirable reaction between VAN-AMB and CS-PEO was not observed. DSC test recognized the uniform distribution of drugs in the polymeric bead of the fiber without any crystal form. The elasticity modulus of the nanofiber was in an acceptable range for oral mucosa (approximately 5 Mpa). The results indicated that biodegradable mucoadhesive nanofibrous membranes released high concentrations of VAN in the first 24 hours, but the AMB release was affected in more controlled phenomena.

本研究采用静电纺丝法制备了直径（d）为116 nm的黏膜黏附性非织造纤维膜，原料按质量分数分别为壳聚糖（80% Wt）、聚环氧乙烷（10% Wt）、半胱氨酸（4% Wt）与药物（6% Wt）。此外，本研究开展对照实验以明确药物及黏膜黏附剂对纳米纤维成纤过程的影响。采用傅里叶变换红外光谱（FTIR）、扫描电子显微镜（SEM）、差示扫描量热法（DSC）以及动态力学分析（DMA）对纳米纤维的化学与物理性能进行表征。通过全浸法开展为期48小时的药物体外释放试验，并将释放数据拟合至零级、一级、Higuchi基质型以及Hixson-Crowell等动力学模型。采用抑菌圈试验评估纤维膜负载的万古霉素与两性霉素B的抑菌活性。SEM图像显示，添加药物与黏膜黏附剂后，纤维直径略有降低。FTIR光谱证实，万古霉素-两性霉素B（VAN-AMB）与壳聚糖-聚环氧乙烷（CS-PEO）之间未发生任何不良反应。DSC测试结果表明，药物在纤维的聚合物基质中分布均匀，未形成任何晶体结构。纳米纤维的弹性模量处于适配口腔黏膜的可接受范围（约5 MPa）。研究结果显示，可生物降解的黏膜黏附性纳米纤维膜在前24小时内可释放高浓度万古霉素，而两性霉素B的释放则受到更为严格的调控。