Lysine-Based C60-Fullerene Nanoconjugates for Monomethyl Fumarate Delivery: A Novel Nanomedicine for Brain Cancer Cells.

In the present study, water-soluble lysine-based C60-fullerene nanoconjugates (CF-LYS-TEG-MMF) were synthesized using a biodegradable linker for the better delivery of monomethyl fumarate (MMF) employing Prato reaction. CF-LYS-TEG-MMF resulted in enhanced cytotoxicity on neuroblastoma cells, meanwhile found to be substantially biocompatible to erythrocytes. The designed nanoconjugate exhibited a pH-based drug release pattern, minimizing the leaching of drug at plasma pH. However, the carrier offered maximum drug release at cancer cell pH, indicating huge promise in internalization of drug molecules at the site of target. The pharmacokinetics of MMF in rodents was significantly improved in terms of enhanced bioavailable drug fraction in the central compartment, reduced drug clearance, elevated plasma concentrations and prolonged biological residence of drug. Enhanced in vitro efficacy in SH-SY5Y neuroblastoma cells, improved erythrocyte compatibility, high drug loading, and conducive pharmacokinetic profile by CF-LYS-TEG-MMF offers a huge promise in brain drug delivery, dose reduction, and dosage-regimen alteration for the management of brain tumors employing MMF.