Paskiabi Farnoush Asghari, Bonakdar Shahin, Shokrgozar Mohammad Ali, Imani Mohammad, Jahanshiri Zahra, Shams-Ghahfarokhi Masoomeh, Razzaghi-Abyaneh Mehdi
Department of Mycology, Pasteur Institute of Iran, Tehran 13164. Iran; Microbiology Research Center, Pasteur Institute of Iran, Tehran 13164. Iran.
National Cell Bank Department, Pasteur Institute of Iran, Tehran 13164, Iran.
Mater Sci Eng C Mater Biol Appl. 2017 Apr 1;73:130-136. doi: 10.1016/j.msec.2016.12.078. Epub 2016 Dec 18.
In spite of developing new drugs and modern formulations, the treatments of chronic fungal infections are still challenging. Fibrous wound dressings are new suggestions for the treatment of chronic superficial infections. In the present study, we formulated an antifungal agent, terbinafine hydrochloride (TFH), which is a hydrophobic drug, in wound dressings prepared by electrospun polycaprolactone, polycaprolactone/gelatin (50:50 w/w) and gelatin. To obtain more water-stable meshes, the preparations were treated by glutaraldehyde and their properties were determined before and after treatment. The morphology of fibrous meshes was observed by scanning electron microscopy. Drug loading efficiency and release rate were measured by high performance liquid chromatography (HPLC) and the release rate was monitored for 144h. Antifungal tests were performed on Trichophyton mentagrophytes, Aspergillus fumigatus and Candida albicans cultured on Muller-Hinton agar. The toxicity of the meshes was measured after 24h and 14days by MTT assay. Terbinafine loading of polycaprolactone/gelatin (50:50) was 100% and it released the highest amount of TFH too. In antifungal tests, all samples were able to hinderT. mentagrophytes and A. fumigatus but not C. albicans growth among them, polycaprolactone fibers made the largest inhibition zone. In MTT assay, none of prepared samples showed toxicity against L929 cells. Teken together, the prepared TFH-loaded PCL/gelatin electrospun meshes were able to release TFH slowly and in a steady state in time. With respect to no obvious cytotoxicity in MTT assay and stong antifungal activity toward T. mentagrophytesin vitro, these TFH-based meshes could be considered as potential candidates in clinical application as wound dressing for treatment of chronic dermatophytosis.
尽管开发了新药和现代制剂，但慢性真菌感染的治疗仍然具有挑战性。纤维伤口敷料是治疗慢性浅表感染的新建议。在本研究中，我们将抗真菌剂盐酸特比萘芬（TFH）（一种疏水性药物）配制到通过静电纺丝制备的聚己内酯、聚己内酯/明胶（50:50 w/w）和明胶伤口敷料中。为了获得更耐水的网片，制剂用戊二醛处理，并在处理前后测定其性能。通过扫描电子显微镜观察纤维网片的形态。通过高效液相色谱（HPLC）测量药物负载效率和释放速率，并监测144小时的释放速率。对在Muller-Hinton琼脂上培养的须癣毛癣菌、烟曲霉和白色念珠菌进行抗真菌试验。通过MTT法在24小时和14天后测量网片的毒性。聚己内酯/明胶（50:50）的特比萘芬负载量为100%，其释放的TFH量也最高。在抗真菌试验中，所有样品都能够抑制须癣毛癣菌和烟曲霉的生长，但不能抑制白色念珠菌的生长，其中聚己内酯纤维形成的抑菌圈最大。在MTT试验中，制备的样品均未显示对L929细胞有毒性。综上所述，制备的负载TFH的PCL/明胶静电纺网片能够及时缓慢且稳定地释放TFH。鉴于MTT试验中无明显细胞毒性以及对须癣毛癣菌具有较强的体外抗真菌活性，这些基于TFH的网片可被视为临床应用中治疗慢性皮肤癣菌病伤口敷料的潜在候选材料。
