Improved topical delivery of tacrolimus: A novel composite hydrogel formulation for the treatment of psoriasis

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• 作者：Doris Gabriel^a ; ^{doris00gabriel@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Thibault Mugnier^a ; Herve Courthion^a ; Ksanthi Kranidioti^b ; Niki Karagianni^b ; Maria C. Denis^b ; Maria Lapteva^c ; Yogeshvar Kalia^c ; Michael Mö ; ller^a ; Robert Gurny^a
• 关键词：Polymeric nanocarriers ; Tacrolimus ; Skin topical drug delivery ; Methoxy poly (ethylen glycol) hexyl-substituted poly (lactic acid) ; Hydrogel ; Dermatology ; Immune-mediated skin disease
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 November 2016
• 年：2016
• 卷：242
• 期：Complete
• 页码：16-24
• 全文大小：1828 K

文摘

We have developed a composite hydrogel for improved topical delivery of the poorly soluble drug Tacrolimus (TAC) to psoriasis lesions. TAC is efficiently solubilized in methoxy poly- (ethylene glycol) hexyl substituted poly-(lactic acid) (mPEGhexPLA) based nanocarriers. For convenient and patient-friendly topical administration, TAC loaded polymeric nanocarriers were incorporated in a Carbopol® based hydrogel, to yield a composite hydrogel formulation (TAC composite hydrogel). TAC composite hydrogel was designed to have superior pharmaceutical formulation properties, delivery efficiency and local bioavailability, compared to currently available paraffin-based TAC ointments. Composite hydrogel formulations had good local tolerance and showed no signs of immediate toxicity after repeated topical administration in healthy mice. Skin delivery of TAC composite hydrogel in an imiquimod-induced psoriasis mouse model was found to be twice as high as for the commercial formulation Protopic™, used as benchmark. TAC composite hydrogel showed significant improvement in the in vivo and histopathological features of the imiquimod-induced psoriasis model.