Transcutaneous delivery of leflunomide nanoemulgel: Mechanistic investigation into physicomechanical characteristics, in vitro anti-psoriatic and anti-melanoma activity.

Swati Pund, Satish Pawar, Shashikant Gangurde, Deepali Divate

文献索引：Int. J. Pharm. 487 , 148-56, (2015)

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摘要

The present study is a mechanistic validation of 'proof of concept' of effective topical delivery of leflunomide (LFD) nanoemulgel for localized efficient treatment of psoriatic lesions as well as melanoma affected skin regions. Hyperproliferation of keratinocytes in psoriasis and symbiotic relationship between keratinocytes and melanocytes, justifies the need of dual acting treatment. LFD is recently introduced significantly effective disease modifying anti-rheumatic drug and has been considered valuable for the treatment of psoriatic arthritis as well as melanoma. Current available treatments for psoriasis and melanoma are inefficient due to systemic side effects, poor transcutaneous permeation and thus present a challenge for development of novel colloidal carriers. We newly reformulated LFD as a nanoemulgel based on self nanoemulsifying technique using Capryol 90, Cremophor EL, Transcutol HP as nanoemulsifying components and Pluronic F127 as a gelling agent. This thermodynamically stable nanoemuslsifying preconcentrate after gelation showed mean globule size, 123.7 nm and viscosity 9620 ± 93 cp. Complete mechanical characterization was carried out using Texture Analyzer and hardness, adhesiveness and springiness index were found to be 523 gms, 431 gms and 1.02, respectively. Ex vivo permeation through rat abdominal skin revealed significant improvement in flux, apparent permeability coefficient, steady state diffusion coefficient and drug deposition in skin due to nanoemulsification of LFD. The in vitro cytoxicity of LFD nanoemulgel in human HaCaT, melanoma A375 and SK-MEL-2 cell lines showed significantly enhanced therapeutic response. In gist, LFD nanoemulgel for trancutaneous delivery will reduce the overall dose and drug consumption, by effectively localizing at the applied target site and will ultimately minimize systemic side effects.Copyright © 2015 Elsevier B.V. All rights reserved.