Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis
Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis
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DOI：
10.1016/j.colsurfb.2016.01.021
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发表时间：
2016-05-01
影响因子：
5.8
通讯作者：
Fratoddi, Ilaria
中科院分区：
文献类型：
--
作者：
Bessar, Hagar;Venditti, Iole;Fratoddi, Ilaria
金纳米颗粒（AuNP）具有尺寸小、一般无毒、易于功能化和高表面积与体积比等优点，是局部给药系统的有效选择。即使全身，甲氨蝶呤仍然发挥着重要的作用，在银屑病治疗：其局部使用显示不足的经皮渗透，由于有限的被动扩散，高分子量和解离在生理pH值。我们的研究的目的是设计一种新的药物输送甲氨蝶呤纳米载体，并提高其溶解度，稳定性和生物分布。金纳米粒子特意制备有亲水稳定层，以提高其在水中的胶体稳定性。制备了3-巯基丙磺酸钠功能化的水溶性金纳米粒子（Au-3 MPS），并将其负载于甲氨蝶呤（MTX）上。MTX在Au-3 MPS上的负载效率被评估为在70- 80%的范围内，具有快速释放（在1小时内80%）。研究了长达24小时的释放，达到95%的值。Au-3MPS@MTX缀合物通过光谱技术（UV-vis、FTIR）和DLS充分表征。在角质形成细胞单层存在下的初步毒性试验允许评估所用的Au-3 MPS没有毒性。然后将缀合物局部用于C57 BL/6小鼠正常皮肤上以追踪吸收行为。STEM图像清楚地显示了金纳米颗粒在细胞内的分布。体外研究表明，与Au-3 MPS缀合的甲氨蝶呤比单独的甲氨蝶呤有效得多。此外，基于MTT分析，通过纳米颗粒缀合的存在，DL 50在48小时降低20倍。应用24小时后，在裸小鼠皮肤上体内追踪缀合物的紫外-可见光谱显示，与单独的MTX相比，使用Au-3MPS@MTX缀合物，甲氨蝶呤在表皮和真皮中的递送增加。此外，我们观察到在真皮和表皮中不存在Au-3 MPS，表明皮肤的这些层不保留纳米颗粒。基于我们的数据，我们发现新的Au-3MPS@MTX缀合物是甲氨蝶呤令人满意的经皮吸收的有效无毒载体，并且可能有助于银屑病的可能的局部治疗。(C)2016爱思唯尔B. V.保留所有权利。
Gold nanoparticles (AuNPs) represent an effective choice for topical drug delivery systems thanks to their small size, general non-toxicity, ease of functionalization and high surface to volume ratio. Even if systemic, methotrexate still plays an important role in psoriasis treatment: its topical use shows insufficient percutaneus penetration owing to limited passive diffusion, high molecular weight and dissociation at physiological pH. The aim of our study was to design a new drug delivery nanocarrier for Methotrexate and to improve its solubility, stability and biodistribution. AuNPs were on purpose prepared with a hydrophilic stabilizing layer, in order to improve the colloidal stability in water. Water-soluble gold nanoparticles functionalized by sodium 3-mercapto-1-propansulfonate (Au-3MPS) were prepared and loaded with methotrexate (MTX). The loading efficiency of MTX on Au-3MPS was assessed in the range 70-80%, with a fast release (80% in one hour). The release was studied up to 24 h reaching the value of 95%. The Au-3MPS@MTX conjugate was fully characterized by spectroscopic techniques (UV-vis, FTIR) and DLS. Preliminary toxicity tests in the presence of keratinocytes monolayers allowed to assess that the used Au-3MPS are not toxic. The conjugate was then topically used on C57BL/6 mouse normal skin in order to trace the absorption behavior. STEM images clearly revealed the distribution of gold nanoparticles inside the cells. In vitro studies showed that Methotrexate conjugated with Au-3MPS is much more efficient than Methotrexate alone. Moreover, DL50, based on MTT analysis, is 20 folds reduced at 48 h, by the presence of nanoparticles conjugation. UV-vis spectra for in vivo tracing of the conjugate on bare mouse skin after 24 h of application, show increased delivery of Methotrexate in the epidermis and dermis using Au-3MPS@MTX conjugate, compared to MTX alone. Moreover we observed absence of the Au-3MPS in the dermis and in the epidermis, suggesting that these layers of the skin do not retain the nanoparticles. Based on our data, we found that the novel Au-3MPS@MTX conjugate is an effective non-toxic carrier for the satisfactory percutaneous absorption of Methotrexate and could help in possible topical treatment of psoriasis. (C) 2016 Elsevier B.V. All rights reserved.