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Therapeutic Hydrogels of Nonsteroidal Anti-Inflammatory Drugs

总结: · Oligopeptidescomprising D-amino acids to replace L-amino, produce protease resistant motifs

技术优势: Bio stableand biocompatible supramolecular hydrogels of D-peptides and therapeutic smallmolecules increase target selectivity and decrease adverse drug reactionsTheinvention confers proteolytic resistance and preserves drug activity forsustained releaseAdministered as topical gels or creams to use for relieving pain induced bylocal inflammationThetherapeutic hydrogels serve as a cheap, safe, and effective carrier for drug toreduce ADRsThesynthetic route for said peptidic conjugate is facile, well established, andeasy to scale up

详细技术说明: Therapeutic Hydrogels of Nonsteroidal Anti-Inflammatory Drugs:D-peptides/NSAIDs conjugates boost drugselectivity and reduce side effects

*Abstract: Background:
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely andsystematically used in high doses for the treatment of acute or chronic painsand inflammations. NSAIDs effectively relieve pain and treat inflammation bybinding to the cyclooxygenase-2 (COX-2) enzyme. However, NSAIDs also inhibitCOX-1, which causes adverse drug effects (ADRs) such as: gastrointestinal ulceration,stomach bleeding, renal failure, and cardiovascular risks. ADRs not only limitthe use of otherwise effective drugs, but also lead to the attrition of newdrugs in clinical trials.
Until now, nosimple and general approach for reducing “off-target” effects of NSAIDs hasexisted. This invention employs novel multifunctional supramolecularhydrogelators made of unnatural amino acids or peptides (D-amino acids orD-peptides) and an NSAID as a new approach for delivering therapeutic agents bybiostable, target specific, and potent hydrogels. These therapeutic hydrogelsare 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. Thesecompounds may be functionalized with other active agents, such as anticancertherapeutic agents, anti-HIV drugs or imaging agents, therefore fulfillingmultiple biomedicinal roles.

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