In recent years, chemical enhancers that increase the permeability of stratum corneum (SC)attracted the attention of clinicians and researchers due to their utility in developing transdermal drug deliverysystems. N-Lauroyl glycine lauryl ester (NLGLE) was reported to induce higher SC permeability than N-lauroyl serine lauryl ester (NLSLE). Earlier, we proposed a similar activity could be obtained by N-acyl-L-alanine esters (NAAEs) towards SC, which are homologous to NLGLE. In this study, we synthesized ahomologous series of N,O-diacyl-L-alaninols (DAAOHs) (which are isomers of NAAEs) with saturated acylchains. We investigated their thermotropic phase behavior and supramolecular organization, and the resultsare discussed with the properties of isomeric NAAEs. Most DAAOHs exhibited one polymorphic phasetransition (solid-solid transition) before the melting transition in the first heating thermogram. The solid-solidtransition disappeared in further heating thermograms. Odd chainlength DAAOHs exhibited higher transitionenthalpy and transition entropy values than even chainlength DAAOHs. Interestingly, the even chainlengthDAAOHs exhibited higher transition temperature and d-spacing values than odd chainlength DAAOHs.Further, Laurdan fluorescence studies revealed that N,O-dilauroyl-L-alaninol increases the fluidity of SCmodel membrane more efficiently as compared to NLGLE, suggesting that DAAOHs can potentially be usedas chemical enhancers in developing transdermal drug delivery systems.
Synopsis: PXRD and DSC studies on N,O-diacyl-L-alaninols (DAAOHs) indicate that odd- and even chainlength compounds exhibit differences in molecular packing, and odd-even alternation in transition enthalpies of the solid-liquid transition. N,O-Dilauroyl-L-alaninol increased the fluidity of stratum corneum model membrane, suggesting that DAAOHs would be useful in designing transdermal drug delivery systems.