Redesigning Ibuprofen for Improved Oral Delivery and Reduced Side Effects.

Ibuprofen (IBP) is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs). Being well-known for its efficacy, long history of use, and reduced adverse events compared to other NSAIDs, IBP is authorized as an analgesic and antipyretic drug. IBP's mechanism of action consists of inhibiting cyclooxygenases, which are crucial oxidoreductases in prostaglandin synthesis and generation of inflammation and pain. However, despite being effective and relatively safe, IBP can still induce a dose-dependent toxicity which manifests mainly in the gastrointestinal system as ulcerations and altered mucosal blood flow and cytotoxicity characterized by mitochondrial dysfunction and increased membrane permeability in enterocytes and hepatocytes. Therefore, ongoing research is performed to improve the IBP's activity and treatment outcome, and one way to achieve such improvements is through reducing IBP's toxicity by designing less harmful but still effective novel IBP conjugates. The aim of this review is to summarize the latest achievements with IBP conjugation techniques that created such valuable IBP formulations less toxic than but as effective as the parent drug.