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

Gold nanoparticle (AuNP) are potential drug delivery systems thanks to their small size, general non-toxicity, ease of functionalization and high surface to volume ratio. AuNPs could represent an effective choice for topical drug delivery. Methotrexate plays an important role in psoriasis treatment with insufficient percutaneous penetration owing to limited passive diffusion and dissociation at physiological pH. We propose a new design for Methotrexate delivery nanocarrier to improve its solubility, stability and biodistribution. AuNPs were prepared with an hydrophilic stabilizing layer. The AuNPs@MTX bioconjugate was fully characterized by spectroscopic techniques (UV-vis, FTIR) and DLS. MTX bioconjugated on the AuNPs showed a loading of about 80%. A release of 95% was obtained in 24 hours. The new AuNPs@MTX bioconjugate was tested on keratinocytes monolayer and Skin Equivalent in order to assess the toxicity and proper dose. The bioconjugate was topically used on C57BL/6 mouse normal skin to trace absorption and drug delivery. In vitro studies showed that AuNPs@MTX is much more efficient than Methotrexate alone, proved by (TEM) Transmission electron microscopy. Moreover, DL50 is ten folds reduced at 48 hours by the presence of nanoparticles conjugation based on MTT analysis. UV-vis spectra for in vivo tracing of the conjugate after 24 hours of application on bared rat skin show successful delivery of Methotrexate in the epidermis and in less intensity also in the dermis, in spite of absence of the AuNPs neither in the dermis nor in the epidermis, suggesting that both layers of the skin does not retain the nanoparticles. Based on our research, we found the novel AuNPs@MTX is an effective nontoxic carrier for the satisfactory percutaneous absorption of Methotrexate and could help in possible topical treatment of psoriasis.