Technologies

Therapeutic Hydrogels of Nonsteroidal Anti-Inflammatory Drugs:

D-peptides/NSAIDs conjugates boost drug selectivity and reduce side effects

Background:

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely and systematically used in high doses for the treatment of acute or chronic pains and inflammations. NSAIDs effectively relieve pain and treat inflammation by binding to the cyclooxygenase-2 (COX-2) enzyme. However, NSAIDs also inhibit COX-1, which causes adverse drug effects (ADRs) such as: gastrointestinal ulceration, stomach bleeding, renal failure, and cardiovascular risks. ADRs not only limit the use of otherwise effective drugs, but also lead to the attrition of new drugs in clinical trials.

Until now, no simple and general approach for reducing “off-target” effects of NSAIDs has existed. This invention employs novel multifunctional supramolecular hydrogelators made of unnatural amino acids or peptides (D-amino acids or D-peptides) and an NSAID as a new approach for delivering therapeutic agents by biostable, target specific, and potent hydrogels. These therapeutic hydrogels are stable scaffolds for long-term drug release and significantly reduce ADRs, boosting the selectivity for COX-2 over COX-1 by more than 20 times. These compounds may be functionalized with other active agents, such as anticancer therapeutic agents, anti-HIV drugs or imaging agents, therefore fulfilling multiple biomedicinal roles.