Loading of 5-fluorouracil onto Halloysite nanotubes for targeted drug delivery using a subcritical gas antisolvent process (GAS)

Halloysite clay nanotubes are efficient biocompatible nanocarriers for pharmaceutical products. A gas antisolvent (GAS) process employing subcritical carbon dioxide delivers a product with high loading (43 %) and free of residual solvent. An anticancer agent, 5-fluorouracil, was loaded on nanoclay particles. A quantitative distinction is made between tightly-bound (adsorbed) and loosely-bound (co-precipitated) drug. The physical stages of the dense gas process are clearly outlined. The strongly attached drug is released completely at pH - 7.4 but only up to 30 % in pH = 1.2. The release follows first-order kinetics with a characteristic time of 2 h. The mass ratio of clay nanotubes to 5-fluorouracil affects the loading with adsorbed drug as well as the ratio of loose to tightly attached drug molecules. The system Halloysite-5-fluorouracil can be implemented in drug delivery systems to achieve a desired release profile. The GAS process is a one-pot green process with a low solvent consumption and high-purity product. (C) 2020 Elsevier B.V. All rights reserved.