Synthesis, characterization, kinetic drug release and anticancer activity of bisphosphonates multi-walled carbon nanotube conjugates

Abstract

The statistical proof that most forms of cancer metastasize to bone tissue has redirected research focus to the development of efficient secondary bone cancer treatment regimens. Bisphosphonates (BPs) have been earmarked as a drug of choice for bone metastasis. However, they have a shortcoming of being released before reaching targeted sites due to their low molecular weight. In haste to attain increased efficacy, there is a tendency for drug overdose to occur, resulting in systemic toxicity. One way to curb this is by employing drug delivery systems for targeted and controlled release of the drugs. Having been explored as versatile and innovative drug carriers, multi-walled carbon nanotubes (MWCNTs) have emerged as potential drug delivery systems. Hence, in the present study, alendronate, neridronate and pamidronate are three classes of bisphosphonates that were conjugated onto multi-walled carbon nanotubes. Conjugation was confirmed by characterization techniques including SEM, TEM, EDX, FTIR, Raman and TGA. Drug release studies were also conducted at pH 1.2, 5.5 and 7.4 to study the mechanism of release for neridronate. Results obtained were fitted into Zero order (42.6%), Higuchi (26%) and Korsmeyer-Peppas (22%). The best models describing the release of neridronate from MWCNTs were Zero order, Higuchi and Korsmeyer-Peppas at pH 1.2, 5.5 and 7.4, respectively. A tetrazolium cell viability assay was performed to assess the anticancer activity of the MWCNTs conjugated BPs.

Keywords: Anticancer activity; Bisphosphonates; Drug release; Multi-walled carbon nanotubes; Multi-walled carbon nanotubes conjugates; Water-soluble multi-walled carbon nanotubes.