Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q3SYG4 (C18)
 23,707 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Comparisons were made of branched vs unbranched saturated fatty acids and cis vs trans unsaturated fatty acids as skin penetration enhancers and primary skin irritants. Skin penetration studies used naloxone base as the diffusant, propylene glycol as the vehicle, and human skin. Maximum naloxone flux was with C9-12-branched and unbranched fatty acids. For C5-14 fatty acids, branched and unbranched isomers had similar effects. One branched C18 fatty acid isomer (C16-branched isostearic acid) was more effective in enhancing skin penetration than a differently branched (C2-branched isostearic acid) or unbranched C18 isomer (stearic acid). There was no significant difference between cis and trans unsaturated C16-18 fatty acid isomers in their effects on naloxone flux, and all unsaturated fatty acids were more effective enhancers than the corresponding saturated isomers. Several of these fatty acid/propylene glycol vehicles were evaluated in a rabbit primary skin irritation test. Irritation indices were poorly correlated with the effectiveness of the vehicles in enhancing naloxone flux. It was possible to enhance naloxone skin penetration greatly with a vehicle with only minimal skin irritation potential.
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PMID:Structure/effect studies of fatty acid isomers as skin penetration enhancers and skin irritants. 272 82

Closed patch testing and the nitrocellulose-replica method are performed as useful clinical methods for the evaluation of human skin irritation by cosmetics and topical medicaments. Comparison of the sensitivity between microscopic scoring by nitrocellulose-replica method and visual scoring by closed patch test in the detection of skin irritation, however, has not been well studied with statistical analysis. Here, we evaluated human skin irritation by carboxylic acids, alcohols, esters and aldehydes, with different chain length (C8-C18), using both methods. The results of closed patch testing showed that, although the score of skin irritation for carboxylic acids (C8, C12), alcohols (C8) and aldehydes (C8), tested at a concentration of 0.5 m-2.0 m, significantly increased with increasing concentration of the test compounds, ester compounds scarcely caused any irritation on the surface of the skin occluded. In addition, an increase of carbon chain length in the test compounds made it impossible to detect skin irritation. In contrast, the nitrocellulose-replica method could evaluate skin reactions against very weak irritants that gave no macroscopic alterations on the skin surface in the closed patch test. However, the scoring system is somewhat subjective and should be improved to make the analysis more objective.
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PMID:Evaluation of human skin irritation by carboxylic acids, alcohols, esters and aldehydes, with nitrocellulose-replica method and closed patch testing. 878 18

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.
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PMID:Conjugates of unsaturated fatty acids with propylene glycol as potentially less-irritant skin penetration enhancers. 1805 12

One of the most widely used approaches for improving drug permeation across the stratum corneum barrier of the skin is the use of chemical penetration enhancers, such as surfactants. In this study, two anionic surfactants, named C12-OPK and C18-OPK, were synthesized via condensation of itaconic acid and fatty amines, with C12 and C18 alkyl chains, respectively. Assessment of impacts on HaCaT keratinocyte cell viability was used as indicator of their potential to cause skin irritation 24h post exposure (Alamar Blue assay). The LC50 values of C12-OPK and C18-OPK (144 and 85mg/L, respectively) were lower than LC50 values of the most used commercial surfactants (e.g. SDS). The effect of different surfactant concentrations (up to ten times the critical micellar concentration, CMC) on hydrocortisone (HC) solubility and permeation through porcine skin was also evaluated. Results showed that drug solubility increased linearly with increasing concentrations of both surfactants, as a consequence of the association between drug and micelles. In vitro permeation results showed that the permeability coefficient increased at surfactant concentrations lower than the CMC. In particular, a higher enhancement effect on drug permeation was obtained with C18-OPK, due to its hydrophobic properties that ensured a more effective HC permeation in comparison to C12-OPK.
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PMID:Surfactants from itaconic acid: Toxicity to HaCaT keratinocytes in vitro, micellar solubilization, and skin permeation enhancement of hydrocortisone. 2835 26

Ionic liquids (ILs) attract significant attention as novel solvents for drug delivery systems because of their ability to solubilize poorly soluble drugs and tune the physiological properties of active pharmaceutical ingredients. For the next generation of IL-based drug delivery systems, biocompatibility is a high priority. In the current study, choline-fatty acids ([Cho][FA]) were used as a biocompatible IL to mediate the dissolution of a water-soluble antigen peptide in an oil-based skin penetration enhancer. Among the candidate fatty acids (C8, C10, C12, C14, C16, C18:0, and C18:1), C18:1 was selected because of its low cytotoxicity and mediation of skin permeability for an antigen peptide. Using IL[Cho][C18:1] and an oil-based penetration enhancer, the flux of transdermal delivery of the peptide increased 28-fold compared with delivery using an aqueous vehicle. Furthermore, the IL-mediated transcutaneous vaccination succeeded in suppressing tumor growth in vivo compared to injection. The skin irritation produced by this formulation was tested using an in vitro 3D constructed skin tissue model and an in vivo histological study, which concluded that the formulation did not cause skin irritation. The results suggest that biocompatible IL-mediated dissolution in an oil-based skin penetration enhancer is a promising strategy for transdermal drug delivery.
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PMID:Biocompatible Ionic Liquid Enhances Transdermal Antigen Peptide Delivery and Preventive Vaccination Effect. 3290 89