Abstract
ObjectivesThis work aimed to design, synthesize and characterize replacement natural moisturizing factor (NMF) composed of modified hygroscopic linear amino acids to pre‐empt or repair skin barrier dysfunction.MethodsFollowing synthesis and characterization, thermo‐gravimetric analysis and quantum mechanics molecular modelling quantified and depicted water binding to the new compounds. Deliquescence relative humidity demonstrated the water‐scavenging ability of the compounds, whereas snake skin moisturizing studies showed they increased water uptake into snake skin.ResultsFrom thermal analysis, N‐hydroxyglycine showed greatest water‐holding capacity followed by N‐hydroxyserine, l‐homoserine and α‐hydroxyglycine; coupled with quantum mechanics molecular modelling, between 8 and 12 molecules of water could associate with each molecule of either N‐hydroxyglycine, N‐hydroxyserine or l‐homoserine. All of our modified amino acids were efficacious and induced similar or greater water uptake compared with the established moisturizing compounds hyaluronic acid, glycerine and urea in snake skin. Incorporated at 10% in Oilatum, N‐hydroxyserine induced >200% greater moisture uptake into dry snake skin compared to treatment with water alone, with efficacy related to the molecule structure and ability to bind to 12 water molecules. Oilatum cream spiked with all our unnatural amino acid hydrotropes increased water uptake into snake skin compared with Oilatum alone.The compound series was designed to elucidate some structure – efficacy relationships. Amino acid chirality did not affect the water‐holding capacity but did affect uptake into skin. Compounds with high melting points and bond energies tended to decrease water‐holding capacity. With isosteric replacement, the more electronegative atoms gave greater water‐holding capacities.ConclusionsThis work demonstrates the potential of unnatural amino acid hydrotropes as skin moisturizers and has developed some predictive ‘rules’ for further design and refinement of chemical structures.
Highlights
Optimal water content in human skin is essential to maintain the excellent barrier properties of this tissue [1]
Underlying the stratum corneum, filaggrin is a protein synthesized in the viable epidermis which is subsequently hydrolysed to generate a complex mixture of hygroscopic free amino acids, amino acid derivatives and salts which together constitute the natural moisturizing factor (NMF) and which is largely responsible for maintaining the water content of the stratum corneum [2,3]
The unnatural linear amino acids were synthesized by methods modified from the literature; a-hydroxyglycine was synthesized with a yield of 97% by the method described by Hoefnagel [18]
Summary
Optimal water content in human skin is essential to maintain the excellent barrier properties of this tissue [1]. It is the outermost layer of this multilayered structure, the stratum corneum, which regulates water loss from the body and acts as a barrier to. It should be noted that there are site-to-site variations in both relative and absolute amino acid contents in NMF with typically lower levels of serine and citrulline recovered from tape strips of the jaw or cheek than from the back, torso or calf [10,11] and lower levels of NMF reported in the cheek when compared to that in the forearm [12]
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