Synthesis of Ibuprofen Conjugated Molecular Transporter Capable of Enhanced Brain Penetration

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.