Improvement of Topical Palmitoylethanolamide Anti-Inflammatory Activity by Pegylated Prodrugs

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• 作者：Diana Tronino ; Roberto Russo ; Carmine Ostacolo ; Angelica Mazzolari ; Carmen De Caro ; Carmen Avagliano ; Sonia Laneri ; Giovanna La Rana ; Antonia Sacchi ; Francesco Della Valle ; Giulio Vistoli ; Antonio Calignano
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：September 8, 2015
• 年：2015
• 卷：12
• 期：9
• 页码：3369-3379
• 全文大小：480K
• ISSN：1543-8392

文摘

A small library of polyethylene glycol esters of palmitoylethanolamide (PEA) was synthesized with the aim of improving the pharmacokinetic profile of the parent drug after topical administration. Synthesized prodrugs were studied for their skin accumulation, pharmacological activities, in vitro chemical stability, and in silico enzymatic hydrolysis. Prodrugs proved to be able to delay and prolong the pharmacological activity of PEA by modification of its skin accumulation profile. Pharmacokinetic improvements were particularly evident when specific structural requirements, such as flexibility and reduced molecular weight, were respected. Some of the synthesized prodrugs prolonged the pharmacological effects 5 days following topical administration, while a formulation composed by PEA and two pegylated prodrugs showed both rapid onset and long-lasting activity, suggesting the potential use of polyethylene glycol prodrugs of PEA as a suitable candidate for the treatment of skin inflammatory diseases.