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.
Improvement of Topical Palmitoylethanolamide Anti-Inflammatory Activity by Pegylated Prodrugs / D. Tronino, R. Russo, C. Ostacolo, A. Mazzolari, C. De Caro, C. Avagliano, S. Laneri, G. La Rana, A. Sacchi, F. Della Valle, G. Vistoli, A. Calignano. - In: MOLECULAR PHARMACEUTICS. - ISSN 1543-8384. - 12:9(2015), pp. 3369-3379.
|Titolo:||Improvement of Topical Palmitoylethanolamide Anti-Inflammatory Activity by Pegylated Prodrugs|
VISTOLI, GIULIO (Penultimo)
|Parole Chiave:||anti-inflammatory effects; antihyperalgesic effects; N-palmitoylethanolamide; pegylated prodrugs; topical delivery; Administration, Cutaneous; Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dermatologic Agents; Drug Stability; Ethanolamines; Hydrolysis; Male; Mice; Models, Molecular; Palmitic Acids; Polyethylene Glycols; Prodrugs; Skin Absorption; 3003; Molecular Medicine; Drug Discovery3003 Pharmaceutical Science; Medicine (all)|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/acs.molpharmaceut.5b00397|
|Appare nelle tipologie:||01 - Articolo su periodico|