PMID:18058312
| Citation |
Ben-Shabat, S, Baruch, N and Sintov, AC (2007) Conjugates of unsaturated fatty acids with propylene glycol as potentially less-irritant skin penetration enhancers. Drug Dev Ind Pharm 33:1169-75 |
|---|---|
| Abstract |
Fatty acids (FA) are well known as efficient enhancers for transdermal delivery of drugs; however, their frequent dermal toxicity limits their regular use. In order to utilize the fatty acid as a safe enhancer devoid of its irritant effect, we have synthesized and evaluated a series of fatty acids conjugated to propylene glycol (FA-PG). Each one of the conjugates was prepared as a mono- or di- acyl ester derivative. The effects of the synthetic enhancers on the porcine skin permeability were evaluated in a diffusion cell system using lidocaine as the model drug. In addition, in vivo examinations in rabbits were preformed for skin toxicological evaluation. The results indicate that among the FA-PG conjugates, oleic acid (C18:1(n-9))-PG, linoleic acid (C18:2(n-6))-PG and alpha-linolenic acid (C18:3(n-3))-PG, mono- or di-esters, enhance the penetration of lidocaine relatively to the vehicle (without enhancer). The conjugates of oleic acid (C18:1(n-9)) and linoleic acid (C18:2(n-6)) with PG have demonstrated a similar enhancing effect as the corresponding free fatty acids. Interestingly, although the mono- or the di- conjugates of alpha-linolenic acid (C18:3(n-3)) with PG enhanced the lidocaine flux as the other two fatty acid conjugates, they resulted in a reduced permeability as compared to the action of their free acid. In addition, the mono-conjugates of alpha-linolenic acid (C18:3(n-3)) with PG exhibited elevated skin irritation in rabbits (relative to the fatty acid alone) compared to the significantly reduced irritation of oleate-PG and linoeate-PG mono-conjugates. In conclusion, except saturated FA-PG and alpha-linolenic acid (C18:3(n-3)) - PG mono-conjugates, unsaturated fatty acids (e.g., oleic and linoleic acids) after conjugation to PG may be safe and effective enhancers for delivering topical drugs. |
| Links |
PubMed Online version:10.1080/03639040701199258 |
| Keywords |
Animals; Fatty Acids, Unsaturated/chemistry; Fatty Acids, Unsaturated/toxicity; Irritants/toxicity; Lidocaine/administration & dosage; Lidocaine/chemistry; Linoleic Acid/chemistry; Male; Oleic Acid/chemistry; Permeability; Polyethylene Glycols/chemistry; Rabbits; Skin/drug effects; Skin/metabolism; Swine; alpha-Linolenic Acid/chemistry |
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