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Improvement of Topical Palmitoylethanolamide Anti-Inflammatory Activity by Pegylated Prodrugs

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. Mol Pharm. 2015;12(9):3369-79.

Laboratory studyOther animalsTopicalWith polyethylene glycol (PEG) prodrugs of PEA, tested alone as modified forms of PEA

This study tested palmitoylethanolamide together with polyethylene glycol (PEG) prodrugs of PEA, tested alone as modified forms of PEA. Its results cannot be assigned to palmitoylethanolamide alone. More combination studies.

Design
Laboratory study
Subjects
Skin-accumulation and chemical-stability studies of a library of PEA-PEG ester prodrugs, with in silico enzyme modelling
Dose used in the study
Various pegylated PEA prodrugs applied topically to skin
Duration
Effects tracked up to 5 days after topical application
What was measured
Skin accumulation of the prodrugs, chemical stability, in vitro enzymatic breakdown, and duration of pharmacological activity.

What the authors reported

The pegylated prodrugs delayed and extended PEA's activity by changing how it accumulated in skin, particularly when the prodrug had a flexible structure and lower molecular weight. Some prodrugs extended activity to 5 days after a single topical dose, and one formulation combining PEA with two pegylated prodrugs gave both fast onset and long-lasting activity.

Limits of this study

A laboratory and skin-accumulation study; it does not show clinical effect in people with skin inflammation. Funding and conflicts not stated in the abstract.

Source

PubMed 26289562 · doi:10.1021/acs.molpharmaceut.5b00397

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.