Dual modules-molecularly imprinted patch-enabled enantioselectively controlled release of racemic drugs for transdermal delivery.

ABSTRACT

Over 90 % of chiral drugs applied in transdermal drug delivery system (TDDS) are racemates, significantly increasing risks of side effects. Herein, we designed a chiral molecularly imprinted patch (CMIP) that achieved enantioselectively controlled release of S-enantiomers (eutomers) and inhibited the release of R-enantiomers (distomers) for transdermal drug delivery. It is composed of chiral pressure sensitive adhesive (PSA) and molecularly imprinted polymers (MIP), showing better transdermal delivery of S-enantiomers than that of R-enantiomers in vitro (1.86-fold) and in vivo (3.74-fold), significantly decreasing the intake of distomers. Additionally, synthesized fluorescent probe enantiomers visualized enantioselective process of CMIP. Furthermore, investigations of molecular mechanism indicated that dependence on spatial conformation was dominant. On one hand, imprinted cavity of MIP with D-isomer and stronger chiral interaction with R-enantiomers led to more specific adsorption. On the other hand, L-isomer of PSA controlled the release of S-enantiomers by multiple interaction including chiral H-bond, π-π interaction and Van der Waals force. Tthus, the innovatively designed transdermal patch with enantioselective ability released eutomers of racemate and simultaneously inhibited release of distomers, significantly improving therapeutical efficiency and avoiding overdose.