Topical Palmitoylethanolamide anti-Inflammatory activity and prodrugs

The authors state that data indicate that topically administered PEA formulations inhibit inflammation and reduce dermatitis related to its property as a PPAR-α agonist. They point out that such topical PEA formulations have been proven to be an effective therapeutic tool in different skin disorders such as dermatitis, pruritus, psoriasis,and skin barrier disruption. However, the fact that it is widely reported that repeated daily topical administration of PEA are necessary to achieve pharmacological effects should perhaps be improved by chemical derivatives of PEA, so called pro-drugs. This chemical modification of PEA’s pharmacokinetic properties would theoretically perhaps lead to a sustained and prolonged biological activity, as well as a better compliance.

The goal of their chemical synthesis work was to synthesize a small library of PEA polyethyleneglycol derivatives with sustained topical delivery and prolonged pharmacological efficacy. Skin accumulation was of PEA and these prodrugs was evaluated via topical application of PEA and its prodrugs in mice. PEA and its derivatives were also tested in for their anti-inflammatory and antihyperalgesic effects in a murine model of inflamed skin.

An increase in the number of ethylene glycol units leads to improved skin accumulation, however better penetration of certain new chemical entities did lead to a reduced biological effect, such as in the 7th pea derivative. Other molecules did not penetrate and were devoid of clinical effects. Some other prodrugs however did result in better efficacy compared to PEA.

One of the issues not discussed was, that in case of the identification of a new chemical derivative of the natural PEA, the molecule will be considered as a new chemical entity, and development of such drug as a topical treatment takes many, many years.

For the time being PEA cream stays the hallmark of treating various skin disorders based on a natural way to bring balance to inflammed skin, without side effects.

Source: Diana Tronino et al. Improvement of Topical Palmitoylethanolamide Anti-Inflammatory Activity by Pegylated Prodrugs.
DOI: 10.1021/acs.molpharmaceut.5b00397
Mol. Pharmaceutics 2015/07/15.

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