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

Abstract

a b s t r a c tGold 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. Watersoluble 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.

Functionalized platinum nanoparticles with surface charge trigged by pH: synthesis, characterization and stability studies

“…6 for different regions of the Pt/DEA 1:0.25 sample) evidenced the presence of small and uniform PtNPs, with diameter ≈5 nm, having a smaller diameter with respect to the DLS data, as already observed for similar compounds [43]. In fact, the hydrodynamic diameters given by DLS are usually larger than the number average diameter of the particles, and DLS overestimates the average particle sizes [44].…”

Comparative evaluation of immunohistochemistry and real-time PCR for measuring proinflammatory cytokines gene expression in livers of rats treated with gold nanoparticles

“…Previous studies have shown the usefulness of GNPs for the delivery and controlled release of several types of chemical agents including anticancer drugs (Craig et al, 2012), antibiotics (Perni and Prokopovich, 2014), antibodies (Cabezón et al, 2015), vaccines (Chiodo and Marradi, 2015), amino acids (Ipe et al, 2003), peptides (Prades et al, 2012), proteins (Ryou et al, 2014), antioxidants (Simpson et al, 2013) and nucleic acids (Ekin et al, 2014). GNPs functionalized by sodium 3-mercapto-1-propansulfonate and loaded with methotrexate could be an effective and non-toxic regimen for satisfactory percutaneous absorption of methotrexate that could help in possible topical treatment of psoriasis (Bessar et al, 2016). Labala et al (2015) demonstrated the feasibility of using layer-by-layer polymer coated GNPs as a carrier for topical iontophoretic delivery of imatinib mesylate for the treatment of melanoma.…”

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“…Thus GNP conjugate can be used as non-toxic carrier for the satisfactory percutaneous absorption of methotexate and can help in topical treatment of psoriasis. 29 …”