Synthesis and study of deuterated and polyene analogs of selected transdermal permeation enhancers

Martin Psík Charles University in Prague, Faculty of Pharmacy in Hradec Králové 2015 Synthesis and study of deuterated and polyene analogs of selected transdermal permeation enhancers Transdermal drug delivery offers many advantages over traditional routes of administration. Main factor limiting permeation of the drug is barrier property of the skin especially its uppermost layer stratum corneum. One of the approaches to promote drug flux through SC uses permeation enhancers. Most permeation enhancers are not suitable for clinical use due to their toxicity or irritation potential. Interesting family of permeation enhancers are amino acid derivatives, in particular for their low toxicity. Very promising amino acid derivatives seem to be dodecyl 6-dimethylaminohexanoate (DDAK) and dodecyl (S)-N-acetylprolinate (L-Pro2). Their mechanism of action is not fully understood. The main goal of this diploma thesis was to contribute to the understanding of the behavior of these two transdermal permeation enhancers in the skin. In the first part of this thesis deuterated analogues of DDAK and Pro2 with deuterated dodecyl chains (previous studies show no difference between L- and D-Pro2, thus, we only used Pro2) were prepared and then their influence on the SC lipids and proteins were studied by infrared..