Abstract
Based on the strong evidences between inflammation and neurodegeneration, nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are considered as effective agents to reduce the risk of Alzheimer’s and Parkinson’s disease. However, the clinical use of NSAIDs in these diseases is limited by low brain distribution. In this study, we had synthesized ibuprofen conjugate which has good brain penetration.S-(+)-Ibuprofen was covalently attached to a molecular transporter having FITC and eight terminal guanidine groups. This conjugate showed good cellular uptake property in live cells. It was also injected into a mouse and the distribution of the compound was examined in each organ. The conjugate was well delivered to mouse brain indicating the conjugate is able to cross the blood-brain barrier. Our novel synthetic ibuprofen conjugate will hopefully deliver other NSAIDs into brain and is therefore applicable to the neurodegenerative diseases treatment or prevention.
Highlights
Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation
We have recently developed several types of guanidinerich molecular carriers with high molecular weights and good water solubility that readily cross the blood-brain barrier (BBB) and display efficient distributions in the mouse brain [20, 21]
Since the S-(+) enantiomer of ibuprofen is more active in inhibiting the COX enzymes, the S-(+) isomer was used as a model drug of NSAID
Summary
Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation. These are nonselective inhibitors of two isoforms of cyclooxygenase (COX), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby inhibit the production of hormone-like lipid compounds such as prostaglandins and thromboxane which cause inflammation, pain, fever, and platelet aggregation [1, 2]. The aberrantly activated microglia could induce chronic inflammation and cellular damage by producing diverse cytokines and reactive oxygen species (ROS), accelerating neuronal death and resulting in neurodegenerative disease [8,9,10]. Since NSAIDs can reduce inflammation in brain and allow beneficial effects on preventing or reducing neurodegenerative diseases, along with the principal therapeutic effect (e.g., anti-inflammation) of NSAID, we would focus on its neuroprotective effects
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