Pinto Maria Filipa, Moura Catarina Costa, Nunes Cláudia, Segundo Marcela A, Costa Lima Sofia A, Reis Salette
REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Int J Pharm. 2014 Dec 30;477(1-2):519-26. doi: 10.1016/j.ijpharm.2014.10.067. Epub 2014 Nov 1.
The aim of the present work was to develop and assess the potential of nanostructured lipid carriers (NLCs) loaded with methotrexate as a new approach for topical therapy of psoriasis. Methotrexate-loaded NLCs were prepared via a modified hot homogenization combined with ultrasonication techniques using either polysorbate 60 (P60) or 80 (P80) as surfactants. The produced NLCs were within the nanosized range (274-298 nm) with relatively low polydispersity index (<0.25) and zeta potential values around -40 mV. NLCs demonstrated storage stability at 25°C up to 28 days. The entrapment efficiency of methotrexate in NLC-P60 and -P80 was ∼65%. Cryo-SEM images showed the spherical shape of the empty and methotrexate-loaded NLCs. FT-IR confirmed methotrexate presence within the NLCs. The in vitro release of methotrexate from the NLCs followed a fast release pattern reaching ∼70% in 2h. In vitro skin penetration study demonstrated that methotrexate-loaded NLCs-P60 had higher skin penetration when compared to free methotrexate, suggesting a significant role of drug-nanocarriers on topical administration. Methotrexate-loaded NLC-P60 provided drug fluxes of 0.88 μg/cm(2)/h, higher (P<0.001) than with the free drug (control, 0.59 μg/cm(2)/h). The results indicate the potential of NLCs for the delivery of methotrexate to topical therapy of psoriasis.
本研究的目的是开发并评估载有甲氨蝶呤的纳米结构脂质载体（NLCs）作为银屑病局部治疗新方法的潜力。使用聚山梨酯60（P60）或80（P80）作为表面活性剂，通过改良的热均质结合超声技术制备载有甲氨蝶呤的NLCs。所制备的NLCs粒径在纳米范围内（274 - 298 nm），多分散指数相对较低（<0.25），zeta电位值约为 -40 mV。NLCs在25°C下可稳定储存28天。甲氨蝶呤在NLC - P60和 - P80中的包封率约为65%。低温扫描电子显微镜图像显示了空白和载有甲氨蝶呤的NLCs的球形形状。傅里叶变换红外光谱证实甲氨蝶呤存在于NLCs中。甲氨蝶呤从NLCs的体外释放遵循快速释放模式，2小时内释放量达到约70%。体外皮肤渗透研究表明，与游离甲氨蝶呤相比，载有甲氨蝶呤的NLCs - P60具有更高的皮肤渗透性，表明药物 - 纳米载体在局部给药中具有重要作用。载有甲氨蝶呤的NLC - P60的药物通量为0.88 μg/cm²/h，高于游离药物（对照，0.59 μg/cm²/h，P<0.001）。结果表明NLCs在将甲氨蝶呤递送至银屑病局部治疗方面具有潜力。
