One nanoparticle delivers two different neuroprotective amino acids into ischemic brain and protects against neuronal death in rat cerebral ischemia injury

Abstract

Previous studies have proven that glycine and proline are neuroprotective but have very low permeability through the blood-brain barrier (BBB), which is a major barrier to the application of these neuroprotective amino acids in the therapy of brain injury. In this study, we aimed to develop a therapeutic strategy by which one chitosan nanoparticle could deliver two different neuroprotective amino acids, glycine and proline, into the rat ischemic brain to confer neuroprotection in a rat model of cerebral ischemia-reperfusion (I/R) injury. Using the ion cross-linking method, we developed a preparation in which one chitosan nanoparticle was simultaneously loaded with glycine and proline (AA-NPs). We evaluated the therapeutic potential of AA-NPs in both cell and animal models of cerebral ischemic stroke. We found that the levels of glycine and proline were decreased in the brain tissues of I/R rats. AA-NPs delivered both glycine and proline into the ischemic brain and reduced ischemic neuronal death in both in vitro and in vivo. These results indicated that the dual delivery of glycine and proline via AA-NPs mediated neuroprotective effects, as evidenced by the reduction of neuronal death in both cellular and animal models of ischemic stroke. AA-NPs provide an efficient and potential delivery strategy by which multiple neuroprotective amino acids can be transported into the ischemic brain simultaneously for the treatment of ischemic stroke.