Dose ranging, expanded acute toxicity and safety pharmacology studies for intravenously administered functionalized graphene nanoparticle formulations

• Published in: Biomaterials 2014-08, Vol.35 (25), p.7022-7031
• Main Authors: Kanakia, Shruti, Toussaint, Jimmy D, Mullick Chowdhury, Sayan, Tembulkar, Tanuf, Lee, Stephen, Jiang, Ya-Ping, Lin, Richard Z, Shroyer, Kenneth R, Moore, William, Sitharaman, Balaji
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Advanced Basic Science; Animals; Biocompatibility; Biodistribution; Biomedical materials; Blood; Coated Materials, Biocompatible - chemistry; Coated Materials, Biocompatible - pharmacology; Dentistry; Dextran; Dextrans - chemistry; Dose range; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Graphene; Graphene nanoplatelets; Graphite - administration & dosage; Graphite - chemistry; Half-Life; Kidney - drug effects; Kidney - metabolism; Liver - drug effects; Liver - metabolism; Lung - drug effects; Lung - metabolism; Male; Maximum Tolerated Dose; Nanoparticles - chemistry; Nanostructure; Pharmacology; Rats; Rats, Wistar; Safety; Spleen - drug effects; Spleen - metabolism; Surgical implants; Toxicity; Toxicity Tests, Acute
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2014.04.066

Abstract Graphene nanoparticle dispersions show immense potential as multifunctional agents for in vivo biomedical applications. Herein, we follow regulatory guidelines for pharmaceuticals that recommend safety pharmacology assessment at least 10 – 100 times higher than the projected therapeutic dose, and present comprehensive single dose response, expanded acute toxicology, toxicokinetics, and respiratory/cardiovascular safety pharmacology results for intravenously administered dextran-coated graphene oxide nanoplatelet (GNP-Dex) formulations to rats at doses between 1 and 500 mg/kg. Our results indicate that the maximum tolerable dose (MTD) of GNP-Dex is between 50 mg/kg ≤ MTD