Comparative pH-Responsive Loading and Release of Structurally Distinct Central Nervous System Drugs from Graphene Oxide

Graphene oxide (GO) has emerged as a versatile nanocarrier owing to its large surface area and rich surface chemistry; however, systematic studies correlating drug physicochemical properties with loading and release behavior remain limited, particularly for central nervous system (CNS) therapeutics. Herein, we present a comparative investigation of pH-responsive loading and release of two structurally distinct CNS drugs, d-cycloserine and riluzole, using graphene oxide as a common nanocarrier under identical experimental conditions. Drug loading efficiency and encapsulation efficiency were systematically evaluated as a function of pH, temperature, and initial drug concentration. GO exhibited a higher affinity for d-cycloserine, which is attributed to its greater polarity and hydrogen-bonding capability, whereas riluzole loading was primarily governed by π-π stacking and hydrophobic interactions. Both GO-drug systems displayed pronounced pH-responsive release behavior, with accelerated release under acidic conditions and sustained release at physiological pH. In vitro cytocompatibility studies using SH-SY5Y neuroblastoma cells demonstrated excellent biocompatibility for all formulations. This comparative study elucidates the critical role of drug chemistry in governing GO-drug interactions and provides design insights for graphene-based nanocarriers tailored for CNS drug delivery.