Topical Methotrexate Therapy for Psoriasis

Abstract

In vitro percutaneous penetration of methotrexate is enhanced with 1-dodecylazacycloheptan-2-one (laurocapram [Azone]). Laurocapram-containing methotrexate formulations provide effective local inhibition of epidermal DNA synthesis in the in vivo hairless mouse and minipig models, providing the biochemical rationale for topical use in the treatment of psoriasis. Topical methotrexate (0.1%, 0.5%, and 1%) in a laurocapram-containing formulation was tested in a two-center double-blind pilot clinical study of 42 patients with plaque psoriasis. Drugs were applied twice a day for six weeks, and lesions were scored weekly for erythema, scale, and elevation. An overall improvement of 50% or more in the combined scores for erythema, scale, and elevation was obtained with 0.1% methotrexate (64% of patients), 0.5% methotrexate (59%), and 1% methotrexate (56%) vs the vehicle alone (25%). These preliminary findings suggest that methotrexate preparations that provide adequate percutaneous absorption may have a beneficial effect in the treatment of psoriasis.

A clinical study to determine the efficacy and safety of 1% methotrexate/Azone® (MAZ) gel applied topically once daily in patients with psoriasis vulgaris

“…The magnitude of the overall response was limited, however, possibly due to the severity of disease in the study patients. Also, an earlier study by Weinstein et al 4 . indicated that there may be a greater difference between the active and placebo treatments when MAZ topical gel is applied twice daily rather than once daily, as was the case in this study.…”

“…A previous double‐blind, vehicle‐controlled pilot study has demonstrated that topically applied MTX (0.1, 0.5, and 1.0%), in an Azone formulation, produces a 50% or greater improvement in psoriatic patients following 6 weeks of twice‐daily application 4 . Plasma concentrations of MTX were below the limits of detection throughout the course of the study.…”

“…Although effective, MTX has the potential to induce hepatotoxicity, bone marrow suppression, and other adverse effects, thus limiting its use to severely affected patients and precluding its use in patients with milder disease 1 . To minimize systemic exposure and toxicity associated with orally administered MTX, topical MTX formulations containing Azone (laurocapram), a skin penetration enhancer, are being developed and evaluated 2,3 , 4 …”

Studies on in vitro and in vivo transdermal flux enhancement of methotrexate by a combinational approach in comparison to oral delivery

“…The difference in the results is possibly due to the use of ethyl acetate along with ethanolic solution of menthol, which causes higher lipid extraction. Moreover, the flux in this study is much higher as compared to the other research groups [22][23][24][25][26][27][28][29] . However, direct comparison between the fluxes obtained with different research groups cannot be compared due to the different animal species and membrane employed for the study.…”

“…MTX formulation as a hydrogel patch facilitates sustained drug release 22 in contrast to solution or gel 23 . Various researchers have reported the delivery of MTX by ointments, creams, gels, microemulsions, hydrogels, chemical enhancers, and DC iontophoresis 18,[22][23][24][25][26][27][28][29][30] . Our earlier publication 31 demonstrated the advantages of mDC iontophoresis on transdermal delivery.…”