Nanoparticles prolong N-palmitoylethanolamide anti-inflammatory and analgesic effects in vivo

N-Palmitoylethanolamide showed great therapeutic potential in the treatment of inflammation and pain but its unfavourable pharmacokinetics properties will hinder its use in the clinical practice.A nanotechnology-based formulation was developed to enhance the probability of N-palmitoylethanolamide therapeutic success, especially in skin disease management. Lipid nanoparticles were produced and characterized to evaluate their mean size, xi-potential, thermal behaviour, and morphology. The ability of N-palmitoylethanolamide to diffuse across the epidermis as well as anti-inflammatory and analgesic effects were investigated. Particles had a mean size of about 150 nm and a xi-potential of -40 mV. DSC data confirmed the solid state of the matrix and the embedding of N-palmitoylethanolamide while electron microscopy have evidenced a peculiar internal structure (i.e., low-electrondense spherical objects within the matrix) that can be reliably ascribed to the presence of oil nanocompartments. Lipid nanoparticles increased N-palmitoylethanolamide percutaneous diffusion and prolonged the anti-inflammatory and analgesic effects in vivo. Lipid nanoparticles seem a good nanotechnology-based strategy to bring N-palmitoylethanolamide to clinics. (C) 2016 Elsevier B.V. All rights reserved

Improvement of Topical Palmitoylethanolamide Anti-Inflammatory Activity by Pegylated Prodrugs

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