title: Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis.
abstract: 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 24h 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 24h 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.
authors: Dermatology Department, Faculty of Medicine, Zagazig University, 44519, Sharkia, Egypt.
authors: Hagar
authors: H
authors: Bessar
authors: Department of Chemistry, University Sapienza of Rome, p.le Aldo Moro 5, 00185 Rome, Italy.
authors: Iole
authors: I
authors: Venditti
authors: Department of Dermatology, University of Modena and Reggio Emilia, Italy.
authors: Luisa
authors: L
authors: Benassi
authors: Department of Dermatology, University of Modena and Reggio Emilia, Italy.
authors: Cristina
authors: C
authors: Vaschieri
authors: Department of Dermatology, University of Modena and Reggio Emilia, Italy.
authors: Paola
authors: P
authors: Azzoni
authors: Department of Dermatology, University of Modena and Reggio Emilia, Italy.
authors: Giovanni
authors: G
authors: Pellacani
authors: Department of Dermatology, University of Modena and Reggio Emilia, Italy.
authors: Cristina
authors: C
authors: Magnoni
authors: Dermatology Unit, NESMOS Department, Sapienza University of Rome, Sant'Andrea Hospital, Via di Grottarossa 1037, 00189 Rome, Italy.
authors: Elisabetta
authors: E
authors: Botti
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors: Viviana
authors: V
authors: Casagrande
authors: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors: Massimo
authors: M
authors: Federici
authors: Dermatology Unit, NESMOS Department, Sapienza University of Rome, Sant'Andrea Hospital, Via di Grottarossa 1037, 00189 Rome, Italy.
authors: Antonio
authors: A
authors: Costanzo
authors: Department of Chemistry, University Sapienza of Rome, p.le Aldo Moro 5, 00185 Rome, Italy.
authors: Laura
authors: L
authors: Fontana
authors: Department of Chemistry, University Sapienza of Rome, p.le Aldo Moro 5, 00185 Rome, Italy.
authors: Giovanna
authors: G
authors: Testa
authors: Dermatology Department, Faculty of Medicine, Zagazig University, 44519, Sharkia, Egypt.
authors: Fawzia Farag
authors: FF
authors: Mostafa
authors: Dermatology Department, Faculty of Medicine, Zagazig University, 44519, Sharkia, Egypt.
authors: Samia Ali
authors: SA
authors: Ibrahim
authors: Department of Chemistry, University Sapienza of Rome, p.le Aldo Moro 5, 00185 Rome, Italy.
authors: Maria Vittoria
authors: MV
authors: Russo
authors: Department of Chemistry, University Sapienza of Rome, p.le Aldo Moro 5, 00185 Rome, Italy. Electronic address: ilaria.fratoddi@uniroma1.it.
authors: Ilaria
authors: I
authors: Fratoddi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D065546:Drug Liberation; D006046:Gold / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D053768:Metal Nanoparticles / Q000737:chemistry*; D008727:Methotrexate / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D011565:Psoriasis / Q000188:drug therapy*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013053:Spectrophotometry; D017550:Spectroscopy, Fourier Transform Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: C579787:3-mercapto-1-propanesulfonate; D003879:Dermatologic Agents; D013438:Sulfhydryl Compounds; D006046:Gold; D008727:Methotrexate
keywords: Drug loading; Functionalized nanoparticles; Hydrophilic gold nanoparticles; Methotrexate drug delivery