Supra-molecular assembly and magnetic targeted slow-release effect of "dextran-magnetic layered double hydroxide-fluorouracil" drug delivery system / 药学学报
Acta Pharmaceutica Sinica
; (12): 1390-1398, 2011.
Article
en Zh
| WPRIM
| ID: wpr-323111
Biblioteca responsable:
WPRO
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.
Texto completo:
1
Banco de datos:
WPRIM
Asunto principal:
Espectrofotometría Infrarroja
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Termogravimetría
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Difracción de Rayos X
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Portadores de Fármacos
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Farmacocinética
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Disponibilidad Biológica
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Química
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Dextranos
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Ratas Sprague-Dawley
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Preparaciones de Acción Retardada
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Año:
2011
Tipo del documento:
Article