Graphene oxide as a potential drug delivery system: evaluation of biocompatibility in vivo.

Graphene oxide (GO) has considerable potential as a highly efficient nanocarrier for drug delivery, but many toxicity studies have been limited to a single intravenous injection, which does not provide a complete picture of its biocompatibility in vivo. This study investigates the long-term, dose-related safety profile and systemic inflammatory responses to submicron-sized GO under a repeated-dose regimen relevant to drug-delivery applications. BALB/c mice received repeated intraperitoneal injections of unmodified GO sheets at cumulative doses of 10 mg/kg or 25 mg/kg, with longitudinal monitoring up to 60 days. The 10 mg/kg dose of GO was well tolerated, with no adverse changes in hematological parameters or biochemical markers of hepatic and renal function. In contrast, the 25 mg/kg cumulative dose was associated with a low-grade systemic inflammatory response, characterized primarily by increased circulating neutrophils. Serum biochemistry revealed a non-significant trend toward elevated aspartate aminotransferase activity, while creatinine levels remained unchanged. Overall, our findings delineate dose-related safety considerations for GO-based drug delivery design, validating the lower cumulative dose of 10 mg/kg as well tolerated. The intraperitoneal administration model may also provide a useful alternative for evaluating the systemic effects of GO while avoiding direct intravenous exposure.