Synthesis and preliminary biological evaluation of naproxen-probenecid conjugate for central nervous system (CNS) delivery.

Naproxen, known as the most potent non-steroid anti-inflammatory drugs, is vitally crucial in the treatment of neurodegenerative diseases. However, due to the poor brain penetration ability, it causes serious adverse effects with the therapeutic doses. Predictably, these unfavorable factors have hindered its further application. In this study, a novel brain-targeting conjugate, Nap-Pro, was designed and synthesized. The chemical stability and metabolic stability of this conjugate were determined in phosphate buffer, blood serum and brain homogenate, respectively. The cytotoxicity of Nap-Pro was evaluated in b End. 3 cells. In addition, the brain targeting capacity of Nap-Pro was also investigated in vivo. Importantly, Nap-Pro showed excellent capacity to cross the brain-blood barrier (BBB), suggesting probenecid was a super carrier that enhanced the delivery of drugs into brain. Collectively, the probenecid modification was a promising strategy to develop the novel drug delivery systems for brain targeting.