Cintra Giovana Aparecida de Souza, Pinto Larissa Alvarenga, Calixto Giovana Maria Fioramonti, Soares Christiane Pienna, Von Zuben Eliete de Souza, Scarpa Maria Virgínia, Gremião Maria Palmira Daflon, Chorilli Marlus
Faculdade de Ciências Farmacêuticas, UNESP-Universidade Estadual Paulista, Campus Araraquara, Departamento de Fármacos e Medicamentos, Araraquara, SP, 14800-850, Brazil.
Faculdade de Ciências Farmacêuticas, UNESP-Universidade Estadual Paulista, Campus Araraquara, Departamento de Análises Clínicas, Araraquara, SP 14800-850, Brazil.
Molecules. 2016 Feb 18;21(2):231. doi: 10.3390/molecules21020231.
Methotrexate (MTX) is an immunosuppressive drug for systemic use in the treatment of skin diseases, however, MTX presents a number of side effects, such as hepatotoxicity. To overcome this limitation, this study developed skin MTX delivery surfactant systems, such as a microemulsion (ME) and a liquid crystalline system (LCS), consisting of a glycol copolymer-based silicone fluid (SFGC) as oil phase, polyether functional siloxane (PFS) as surfactant, and carbomer homopolymer type A (C971) dispersion at 0.5% (wt/wt) as aqueous phase. Polarized light microscopy and small-angle X-ray scattering evidenced the presence of hexagonal and lamellar LCSs, and also a ME. Texture profile and in vitro bioadhesion assays showed that these formulations are suitable for topical application, showing interesting hardness, adhesiveness and compressibility values. Rheology analysis confirmed the Newtonian behaviour of the ME, whereas lamellar and hexagonal LCSs behave as pseudoplastic and dilatant non-Newtonian fluids, respectively. In vitro release profiles indicated that MTX could be released in a controlled manner from all the systems, and the Weibull model showed the highest adjusted coefficient of determination. Finally, the formulations were not cytotoxic to the immortalized human keratinocyte line HaCaT. Therefore, these bioadhesive surfactant systems established with PFS and C971 have great potential as skin delivery systems.
甲氨蝶呤（MTX）是一种用于全身治疗皮肤病的免疫抑制药物，然而，MTX存在许多副作用，如肝毒性。为克服这一局限性，本研究开发了皮肤MTX递送表面活性剂系统，如微乳液（ME）和液晶系统（LCS），其由基于二醇共聚物的硅油（SFGC）作为油相、聚醚功能硅氧烷（PFS）作为表面活性剂以及0.5%（重量/重量）的A型卡波姆均聚物（C971）分散体作为水相组成。偏光显微镜和小角X射线散射证明存在六方和层状LCSs，以及一个ME。质地剖面分析和体外生物黏附试验表明，这些制剂适用于局部应用，具有令人感兴趣的硬度、黏附性和可压缩性值。流变学分析证实ME表现出牛顿流体行为，而层状和六方LCSs分别表现为假塑性和膨胀性非牛顿流体。体外释放曲线表明，MTX可以从所有系统中以可控方式释放，并且威布尔模型显示出最高的调整决定系数。最后，这些制剂对永生化人角质形成细胞系HaCaT没有细胞毒性。因此，这些用PFS和C971建立的生物黏附表面活性剂系统作为皮肤递送系统具有巨大潜力。
