The purpose of study was to conjugate and evaluate methotrexate with C60-fullerenes and multi-walled carbon nanotubes (MWCNTs) for better drug delivery to cancer cells, and also to compare these two systems. C60-fullerenes and MWCNTs were functionalized by 1,3-dipolar cycloaddition using glycine and paraformaldehyde. Methotrexate (MTX) was esterified and conjugated to the functionalized carbon-based carriers. The conjugates were characterized for micromeritics and drug conjugation. The systems were evaluated for drug release in various pH, MTT cytotoxicity assay, protein binding, cellular uptake, haemolytic profile and pharmacokinetics. Spectroscopic studies confirmed the successful conjugation of drug to the aminated carbon-based carriers. The developed systems released more drug at the pH of cancer cells to that of the pH of plasma. The carriers were compatible with erythrocytes and offered substantial cytotoxicity. Better cellular uptake was confirmed by confocal laser scanning microscopy. C60-fullerenes/MWCNTs modulated the pharmacokinetic profile of drug in desired manner, resulting in better retention and compartment availability. However, the results from C60-fullerenes were observed to be better than that from MWCNTs. The present findings established the potential of carbon-based aminated nanocarriers for delivery of methotrexate in safer and effective manner.
Keywords: 3-Dipolar cycloaddition; C(60)-fullerenes; Carbon nanotubes; Confocal laser scanning microscopy; Pharmacokinetics.
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