31384-20-0Relevant academic research and scientific papers
Improvement of Topical Palmitoylethanolamide Anti-Inflammatory Activity by Pegylated Prodrugs
Tronino, Diana,Russo, Roberto,Ostacolo, Carmine,Mazzolari, Angelica,De Caro, Carmen,Avagliano, Carmen,Laneri, Sonia,La Rana, Giovanna,Sacchi, Antonia,Della Valle, Francesco,Vistoli, Giulio,Calignano, Antonio
, p. 3369 - 3379 (2015)
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.
Polyethylene glycol derivatives of palmitoylethanolamide and analogous acylethanolamides
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Paragraph 0027, (2014/07/07)
Palmitoylethanolamide (PEA) belongs to a group of endogenous molecules known as acylethanolamides. PEA has a great pharmacological potential based on its anti-inflammatory and analgesic properties, although its use is somewhat limited by the high lipophilic nature of the molecule, thereby impairing its use, particularly by topical and injective routes. Here we report the synthesis, pharmacodynamic and pharmacokinetic characterization of a series of Polyethylene glycol conjugates (esters and carbonates) of PEA and its analogous acylethanolamides, that have improved chemical and physical properties, i.e., higher water solubility and good hydrophilic/lipophilic balance, resulting in (i) improved accumulation in tissues (particularly skin and mucosae), (ii) prolonged release, and (iii) increased bioavailability. In particular, here we report the improvement of PEA and analogous acylethanolamides levels in the tissues - particularly in the skin and mucosae - and their prolonged release due to the improved bioavailability of related conjugates. Pharmacological properties of polyethylene glycol conjugates of PEA have been tested in experimental models of inflammation and inflammation-sustained pain (carrageenan induced oedema and mechanical hyperalgesia), two models in which PEA and analogous acylethanolamides activity has been widely described. Our results demonstrate that conjugates are able to extend the time frame in which PEA and analogous acylethanolamides exert their pharmacological effects. These results clearly indicate that polyethylene glycol conjugates of PEA and analogous acylethanolamides could provide powerful pharmacological tools when a prolonged anti-inflammatory and analgesic action of such molecules is desired.
