d‑Amino
Acids Boost the Selectivity
and Confer Supramolecular Hydrogels of a Nonsteroidal Anti-Inflammatory
Drug (NSAID)
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Abstract
As systemically used therapeutics for treating acute
or chronic
pains or inflammations, nonsteroidal anti-inflammatory drugs (NSAIDs)
also associate with the adverse gastrointestinal and renal effects
and cardiovascular risks. Thus, it is beneficial to develop topical
gels that selectively inhibit cyclooxygenase-2 (COX-2) for the management
of local inflammation. In this work, we demonstrate that the covalent
conjugation of d-amino acids to naproxen (i.e., a NSAID)
not only affords supramolecular hydrogelators for the topical gels
but also unexpectedly and significantly elevates the selectivity toward
COX-2 about 20× at little expense of the activity of naproxen.
This work illustrates a previously unexplored approach that employs d-amino acids for the development of functional molecules that
have dual or multiple roles and exceptional biostability, which offers
a new class of molecular hydrogels of therapeutic agents