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.