Functionalized graphene oxide as a drug carrier for loading pirfenidone in treatment of subarachnoid hemorrhage

Abstract

Subarachnoid hemorrhage (SAH) is a life-threatening disease that causes high morbidity and mortality. Pirfenidone is a SAH drug that prevents secondary bleeding and cerebral infarction. To improve its therapeutic efficacy, this study aimed to employ a functionalized graphene oxide nanosheet (FGO) as a drug carrier loading pirfenidone to treat SAH. The graphene oxide nanosheet was introduced with transcription activator peptide (Tat), followed by functionalization with methoxy polyethylene glycol (mPEG) and loading with pirfenidone. The pirfenidone-loaded FGO (pirfenidone-FGO) exhibits better treatment efficacy than the single pirfenidone due to more effective loading and controlled release of the drug in tissue. The introduction of Tat and mPEG onto GO nanosheet contributes to the ability to cross the blood–brain barrier and the stability in blood circulation of the drug. At lower pH values, the highly efficient release of the drug from the pirfenidone-FGO exerts effective treatment to acidic inflammatory lesion after severe SAH. Besides its treatment function, FGO is also shown as a strong near infrared absorbing material which can be applied in photoacoustic imaging, allowing rapid real-time monitoring with deep resolution of brain tissues after SAH. The treatment efficacy of pirfenidone-FGO for central nervous system injuries is further demonstrated by hematoxylin and eosin staining of coronal brain slices, as well as measurements of brain water content and blood–brain barrier permeability. Our study supports the potential of FGO in clinical application in treatment of SAH.