A novel organic-inorganic microhybrids containing anticancer agent doxifluridine and layered double hydroxides: Structure and controlled release properties

摘要

For fully controlled drug release, it is important to completely understand the microstructure and nature of the layered double hydroxide that ultimately control drug release properties. In this study, a series of novel doxifluridine intercalated Mg-Al-layered double hydroxide (DFUR-LDH) microhybrids were fabricated via the reconstruction method. With increasing aging pH values from 7.2 to 9.5, two different LDH phases with varied basal spacings (d(003)) are formed. The DFUR-LDHr1.7p7.2 with d(003) 1.91 nm presents continuous work-like morphology and possible bilayer interlayer arrangement, while DFUR-LDHr2.0p9.5 with d(003) 0.82 nm possesses discontinuous plate-like morphology and multi-sites interacted interlayer arrangement. Consequently, the in vitro release shows that the former has much longer release duration and a little faster initial release due to the weaker interaction between DFUR and LDH layers than that of the latter. The in vitro release data can be well described by the Bhaskar equation and modified Freundlich model, revealing that the release mechanism of DFUR from DFUR-LDH microhybrids is heterogeneous particle diffusion. Furthermore, the enteric polymer modified DFUR-LDHr1.7p7.2/L00 microspheres present no obvious release in pH 1.2 HCl solution, but continuous release of 79% in pH 6.8 and 7.4 PBS, suggesting a readily controlled release behavior upon the varied medium pH and potential application in colon specific drug delivery in cancer therapy.