The effect of Si/Al ratio and drug loading level on the molecular behaviour and controlled release of 5-fluorouracil from zeolite H-Beta

Abstract

The controlled release of anticancer drug 5-fluorouracil (5FU) from zeolite H-Beta has been studied with varying zeolite composition (Si/Al = 19 and 180), and correlated with its molecular behaviour, studied by quasielastic neutron scattering (QENS) and classical molecular dynamics simulations. The study aimed to understand the effect of increasing the Brønsted acid adsorption site concentration on the release properties of these potential drug delivery materials. A factor of ∼1.5 more 5FU was released from the sample with Si/Al = 180 over the release period, consistent with TGA analysis showing a factor of ∼1.5 more drug was encapsulated in this sample, which may initially seem counterintuitive given that it contains far fewer adsorption sites. Notably, the scale parameter of release from the H-Beta sample with Si/Al = 19 was slightly faster, despite the lower total loading and therefore final amount released from this sample. This slightly faster relative release rate was initially attributed to a lower level of steric ‘crowding’ between 5FU molecules in the H-Beta-19 pore system and thus hindrance to molecular mobility compared to H-Beta-180, consistent with the lower observed molecular loading level. QENS studies probing 5FU molecular motions observed the 5FU to be undergoing localised diffusion in the zeolite Beta intersections in both samples, with a higher proportion of mobile molecules performing this motion in H-Beta-19. This suggested the increased total drug loading in H-Beta-180, and resulting steric hindrance in the pore system, is the significant factor in adsorbed drug behaviour, and potentially the relative release rate from these zeolites. Molecular dynamics simulations probed the effect of increasing the drug loading level in the Beta framework and supported that increasing molecular loading significantly hindered total drug mobility due to favourable molecule–molecule interactions in the pore system. The study illustrates the complex relationship between zeolite composition, resulting drug loading level, molecular behaviour, and subsequent release profiles in the design of microporous controlled release systems for anticancer drug delivery.