Supra-molecular assembly and magnetic targeted slow-release effect of “dextran-magnetic layered double hydroxide-fluorouracil” drug delivery system

The drug-loading system of DMF (dextran - magnetic layered double hydroxide - fluorouracil) was synthesized by “co-precipitation intercalated assembly - dextran composite in situ - solvent conversion” technology.  The crystal-phase characteristic and slow-release performance of DMF were investigated through X-ray diffraction (XRD), infrared spectrum (IR), transmission electron microscopy (TEM), thermogravimetry (TG) and in vitro release experiment.  The targeted transshipment and slow-release effect of DMF system were evaluated by in vivo animal experiment.  It was showed that the XRD of DMF matched with R-sixtetragonum type layered double hydroxide and Fd-3m cubic type ferrite.  IR test demonstrated that the DMF system was a supra-molecular complex consisted of Dextran (DET), magnetic layered double hydroxide (MLDH) and fluorouracil (FU) components.  The two-level supra-molecular MLDH-FU presented six-edge lozenge TEM morphology, with layered characteristics.  DET on the surface of DMF was capable of protecting the layered structure of MLDH-FU, improving particle dispersion properties, and strengthening the slow-release performance of the drug delivery system.  The drug release model of DMF at pH 7.35 of PBS in vitro fit to the zero-order kinetics equation C = 1.171 6 ´ 10⁻⁵ + 4.462 6 ´ 10⁻⁷ t.  The drug delivery system DMF could transport drugs principally to in vivo target organs with a local effect, targeted specificity, and excellent circulation transshipment performance.  The pharmacokinetic process of DMF presented multi-peak phenomenon with peak attenuation and cyclic growth.  The peaks appeared at 0.25, 1, 3, 5 and 9 d separately after dosing intervention.  The first peak process of DMF accorded with a pharmacokinetic equation of C_FU = 14.34 e^{−0.530 t} + 36.04 e^{−0.321 t} + 24.18 e^{−0.196 t}, and presented the characteristic of slow absorption and fast elimination.  As for subsequent peak processes, half-life increased, bioavailability increased, and plasma clearance decreased.  The highest peak value of DMF was 1/37 of original value of FU, and the relative bioavailability was 419% to original FU.