LAQV-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
LAQV-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Int J Biol Macromol. 2019 Mar 1;124:1115-1122. doi: 10.1016/j.ijbiomac.2018.12.014. Epub 2018 Dec 3.
In this study, fucoidan/chitosan nanoparticles were developed for the topical delivery of methotrexate towards the treatment of skin-related inflammatory diseases. Based on the fucoidan/chitosan (F/C) weight ratio, three different nanoparticles (1F/1C; 3F/1C; 5F/1C) were produced and characterized. Methotrexate was loaded in these polymeric nanoparticles achieving a drug loading of ca. 14% and an entrapment efficiency of 96, 87 and 80% for 1F/1C; 3F/1C and 5F/1C nanoparticles, respectively. Methotrexate-loaded fucoidan/chitosan nanoparticles exhibited size within the 300-500 nm range, positive zeta potential for 1F/1C nanoparticles (+60 mV) and negative surface charge for the 3F/1C and 5F/1C nanoparticles (-40 and -45 mV, respectively). Methotrexate loaded in 3F/1C and 5F/1C nanoparticles did not affect cells viability and presented lower cytotoxicity than free methotrexate, in fibroblasts and human keratinocytes. MTX-loaded fucoidan/chitosan nanoparticles lead to a significant reduction of pro-inflammatory cytokines produced by activated human monocytes. Skin permeation studies showed that methotrexate-loaded nanoparticles permeated the pig ear skin barrier reaching after 6 h, a 2.7- and 3.3-fold increase for 3F/1C and 5F/1C nanoparticles, relative to free methotrexate. In conclusion, fucoidan/chitosan nanoparticles, in particular the ratio 5F/1C, is safe, exerts an anti-inflammatory effect and increase skin permeation thus can potentially be used for methotrexate topical delivery.
在这项研究中，开发了褐藻糖胶/壳聚糖纳米粒用于甲氨蝶呤的局部递药，以治疗皮肤相关炎症性疾病。基于褐藻糖胶/壳聚糖（F/C）的重量比，制备并表征了三种不同的纳米粒（1F/1C；3F/1C；5F/1C）。将甲氨蝶呤载入这些聚合物纳米粒中，载药量约为 14%，1F/1C、3F/1C 和 5F/1C 纳米粒的包封效率分别为 96%、87%和 80%。载甲氨蝶呤的褐藻糖胶/壳聚糖纳米粒的粒径在 300-500nm 范围内，1F/1C 纳米粒的zeta 电位为正（+60mV），3F/1C 和 5F/1C 纳米粒的表面带负电荷（-40 和-45mV）。载甲氨蝶呤的 3F/1C 和 5F/1C 纳米粒不影响细胞活力，且细胞毒性低于游离甲氨蝶呤，在成纤维细胞和人角质形成细胞中。载甲氨蝶呤的褐藻糖胶/壳聚糖纳米粒可显著减少激活的人单核细胞产生的促炎细胞因子。皮肤渗透研究表明，载甲氨蝶呤的纳米粒渗透猪耳皮肤屏障，6h 后，3F/1C 和 5F/1C 纳米粒分别是游离甲氨蝶呤的 2.7 倍和 3.3 倍。总之，褐藻糖胶/壳聚糖纳米粒，特别是 5F/1C 比例，安全、具有抗炎作用并增加皮肤渗透，因此可能用于甲氨蝶呤的局部递药。
