α-Aminophosphonates are organophosphorus compounds with an obvious similarity with
α-amino acids. Owing to their biological and pharmacological characteristics, they
have attracted the attention of many medicinal chemists. α-Aminophosphonates are known
to exhibit antiviral, antitumor, antimicrobial, antioxidant and antibacterial activities,
which can all be important in pathological dermatological conditions. However, their
ADMET properties are not well studied. The aim of the current study was to provide
preliminary information about the skin penetration of three preselected α-aminophosphonates
when applying them as topical cream formulations in static and dynamic diffusion chambers.
The results indicate that aminophosphonate 1a, without any substituent in the para
position, shows the best release from the formulation and the highest absorption through
the excised skin. However, based on our previous study, the in vitro pharmacological
potency was higher in the case of para-substituted molecules 1b and 1c. The particle
size and rheological studies revealed that the 2% cream of aminophosphonate 1a was
the most homogenous formulation. In conclusion, the most promising molecule was 1a,
but further experiments are proposed to uncover the possible transporter interactions
in the skin, optimize the topical formulations and improve PK/PD profiles in case
of transdermal delivery.
