title: [Supra-molecular assembly and magnetic targeted slow-release effect of "dextran-magnetic layered double hydroxide-fluorouracil" drug delivery system].
abstract: 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 = 1.1716 x 10(-5) + 4.4626 x 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(-0.530t) + 36.04 e(-0.321t) + 24.18 e(-0.96t), 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.
authors.affiliation: Department of Chemistry, Ningxia Medical University, Yinchuan 750004, China. ggj64@yahoo.com.cn
authors.forename: Guo-jing
authors.initials: GJ
authors.lastname: Gou
authors.forename: Yan-hong
authors.initials: YH
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Je
authors.initials: J
authors.lastname: Huang
authors.forename: Bing
authors.initials: B
authors.lastname: Xue
authors.forename: Li-e
authors.initials: LE
authors.lastname: Dong
mesh_terms: D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000737:chemistry*; D004337:Drug Carriers; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006207:Half-Life; D006878:Hydroxides / Q000737:chemistry*; D008280:Magnetics; D008297:Male; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley; D013055:Spectrophotometry, Infrared; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D003911:Dextrans; D004337:Drug Carriers; D006878:Hydroxides; D005472:Fluorouracil