Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis

被引：114

作者：

Bessar, Hagar ^{[1
]}

Venditti, Iole ^{[2
]}

Benassi, Luisa ^{[3
]}

Vaschieri, Cristina ^{[3
]}

Azzoni, Paola ^{[3
]}

Pellacani, Giovanni ^{[3
]}

Magnoni, Cristina ^{[3
]}

Botti, Elisabetta ^{[4
]}

Casagrande, Viviana ^{[5
]}

Federici, Massimo ^{[5
]}

Costanzo, Antonio ^{[4
]}

Fontana, Laura ^{[2
]}

Testa, Giovanna ^{[2
]}

Mostafa, Fawzia Farag ^{[1
]}

Ibrahim, Samia Ali ^{[1
]}

Russo, Maria Vittoria ^{[2
]}

Fratoddi, Ilaria ^{[2
]}

机构：

[1] Zagazig Univ, Fac Med, Dept Dermatol, Sharkia 44519, Egypt

[2] Univ Roma La Sapienza, Dept Chem, Ple Aldo Moro 5, I-00185 Rome, Italy

[3] Univ Modena & Reggio Emilia, Dept Dermatol, Modena, Italy

[4] Univ Roma La Sapienza, NESMOS Dept, Dermatol Unit, St Andrea Hosp, Via Grottarossa 1037, I-00189 Rome, Italy

[5] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy

来源：

COLLOIDS AND SURFACES B-BIOINTERFACES | 2016年 / 141卷

关键词：

Hydrophilic gold nanoparticles; Drug loading; Methotrexate drug delivery; Functionalized nanoparticles; DRUG-DELIVERY; IN-VITRO; SKIN; CELLS; PENETRATION; METABOLISM; RESISTANCE; MANAGEMENT; ARTHRITIS; THERAPY;

D O I：

10.1016/j.colsurfb.2016.01.021

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

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.

引用

页码：141 / 147

页数：7

共 69 条

[1] Design and optimization of topical methotrexate loaded niosomes for enhanced management of psoriasis: Application of Box-Behnken design, in-vitro evaluation and in-vivo skin deposition study [J].