Co-delivery of terbinafine hydrochloride and urea with an in situ film-forming system for nail targeting treatment
Co-delivery of terbinafine hydrochloride and urea with an in situ film-forming system for nail targeting treatment
复制标题
DOI：
10.1016/j.ijpharm.2020.119497
复制
发表时间：
2020-07-30
影响因子：
5.8
通讯作者：
Xu, Yuehong
中科院分区：
文献类型：
--
作者：
Yang, Fengdie;Yu, Xiuming;Xu, Yuehong
甲真菌病是一种慢性指甲疾病，由真菌感染组成，会导致患者身体和心理社会不适。然而，由于高度角化的指甲板的屏障和传统制剂在指甲上停留的时间较短，其治疗仍然具有挑战性。在这项工作中，我们开发了一种基于Eudradit(R)RLPO的原位成膜系统(IFFS)，用于共传递盐酸特比奈芬(TBH)和尿素，即TBH-尿素-RLPO IFFS，目的是克服指甲屏障，延长滞留时间，并有效治疗甲真菌病。现场应用表明，IFFS配方形成的薄膜具有良好的外观和附着力。利用偏光显微镜和粉末X射线衍射仪对薄膜中的四丁基氢和尿素的物理状态进行了表征。TBH和尿素都是RLPO膜中的无定形可混溶组分。TBH-尿素-RLPO IFFS的释药符合Korsmeyer-Pappas模型，72 h的累积释放量显著高于商业制剂(Lamisil Pedisan(R)ONCE)。比较了TBH-尿素-RLPO IFFS膜与含TBH膜(TBH-RLPO)和商品制剂的体外透皮性能。TBH-尿素-RLPO IFFS的截留率和累积渗透量显著增加(170.80+/-44.63mU/cm(2)vs75.49+/-21.50mg/cm(2)vs60.25+/-27.38mg/cm(2)；分别为61.81+/-16.09 mU/cm(2)和21.80+/-11.56 mU/cm(2)和7.91+/-1.03 mU/cm(2)，并用扫描电子显微镜和傅立叶变换红外光谱观察了不同配方处理的牛蹄角蛋白的变性效果。在Muller-Hinton琼脂上进行了红色毛霉菌、犬小孢子菌、镰刀菌和烟曲霉的体外抗真菌试验，结果表明，TBH-尿素-RLPO IFFS提高了TBH的抗真菌活性。总体而言，研究结果支持TBH-尿素-RLPO IFFS是一种有效且有前景的甲真菌病靶向治疗方法。
Onychomycosis is a chronic nail disorder consisting of a fungal infection that causes physical and psychosocial discomfort to patients. However, its treatment remains challenging owing to the barrier of the highly keratinized nail plate and the short time that conventional formulations reside on nails. In this work, we developed an in situ film-forming system (IFFS) based on Eudragit (R) RLPO to co-deliver terbinafine hydrochloride (TBH) and urea, i.e., TBH-urea-RLPO IFFS, with the aim of overcoming the nail barrier, prolonging the residence time, and efficiently treating onychomycosis. The IFFS formulation formed a thin film with good appearance and adhesion upon application in situ. The physical states of TBH and urea in the film were evaluated with polarization microscopy and powder X-ray diffraction. TBH and urea were both amorphous miscible components within the RLPO film. TBH release from TBH-urea-RLPO IFFS fitted to the Korsmeyer-Pappas model, and the cumulative release at 72 h was significantly higher than that from commercial preparations (Lamisil Pedisan (R) once). In vitro permeation of TBH from TBH-urea-RLPO IFFS through bovine hoof membranes was evaluated in comparison with the film containing TBH alone (TBH-RLPO) and commercial preparations. The retention and cumulative permeated amount of TBH were significantly enhanced for the TBH-urea-RLPO IFFS (170.80 +/- 44.63 mu g/cm(2) vs 75.49 +/- 21.50 mu g/cm(2) vs 60.25 +/- 27.38 mu g/cm(2) ; 61.81 +/- 16.09 mu g/cm(2) vs 21.80 +/- 11.56 mu g/cm(2) vs 7.91 +/- 1.03 mu g/cm(2) , respectively), and the membranes treated with different formulations were observed with SEM and FTIR to identify the denaturing effect of urea on bovine hoof keratin. In vitro antifungal tests against Trichophyton rubrum , Microsporum canis , Fusarium , and Aspergillus fumigatus were cultured on Muller-Hinton agar; the findings indicated that TBH-urea-RLPO IFFS enhanced TBH antifungal activity. Overall, the results support that TBH-urea-RLPO IFFS is an efficient and promising approach for onychomycosis targeting treatment.