Hydroxyethylcellulose as a methotrexate carrier in anticancer therapy

Clinical and experimental cancer therapy is multifaceted; one such facet is the use of drug carriers. Drug carriers are various nano- and macromolecules, e.g., oligosaccharides, proteins, and liposomes. The present study aimed to verify the suitability of cellulose as a carrier for methotrexate (MTX). Hydroxyethylcellulose, with a molecular weight of 90 kDa and soluble in water, was used. Methotrexate was linked to cellulose by methyl ester bonds. A conjugate containing on average 9.5 molecules of MTX per molecule of cellulose was developed. Gel filtration HPLC analysis showed that the conjugate contained approximately 2% free drug. Dynamic light scattering analysis showed an increase in the polydispersity of the conjugate. The degradation of the conjugate in phosphate buffer and plasma followed first-order kinetics. The conjugate showed the lowest stability (half-life 154 h) in plasma. The conjugate showed 10-fold lower cytotoxicity to the 4 T1 mammary tumour cell line than the free drug. In the in vivo experiment to treat orthotopically implanted mammary tumours, the conjugate and the free drug, both applied intravenously, showed maximum inhibition of tumour growth of 48.4% and 11.2%, respectively. In conclusion, cellulose, which is a non-biodegradable chain glucose polymer, can be successfully used as a drug carrier, which opens up new research perspectives.

Automated summary

The study confirmed the suitability of cellulose as a carrier for methotrexate in cancer therapy, showing potential applications in reducing drug toxicity to normal cells and inhibiting tumor growth. The cellulose-methotrexate conjugate demonstrated lower cytotoxicity and higher inhibition of tumor growth compared to free drug, highlighting new research perspectives in drug delivery systems.