Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 436, Issue 1-2, Pages 272-281Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2012.06.022
Keywords
Supercritical CO2; 5-Fluorouracil; Poly(L-lactic)-polyethylene glycol; Reverse emulsion-SEDS; Nanoparticles; Drug delivery system
Categories
Funding
- Major scientific and technological specialized project of China for 'significant new formulation of new drugs' [2009ZX09103-709]
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In this work, 5-fluorouracil-loaded-poly(L-lactic)-polyethylene glycol/polyethylene glycol (5-FU-loaded-PLLA-PEG/PEG) nanoparticles were prepared using a novel reverse emulsion-solution enhanced dispersion by supercritical fluids (reverse emulsion-SEDS) technique in an effort to obtain an efficient drug delivery system. In the experiment, 5-FU and PEG were dissolved in water PLLA-PEG was dissolved in organic solution, the aqueous solution was added dropwise to the organic solution under magnetic stirring, a reverse emulsion was immediately formed. The reverse emulsion was dried by a SEDS process so that 5-FU-loaded-PLLA-PEG/PEG nanoparticles (5-FU-NPs) were obtained. The particle size, size distribution, surface morphology, and physical and chemical properties of the 5-FU-NPs were investigated by laser diffraction particle size analysis, scanning electron microscopy (SEM), Fourier transform infrared spectrometry (FTIR) and thermogravimetric analysis (TGA). The drug encapsulation efficiency (EE), drug loading (DL), in vitro release profile and pharmacokinetics of 5-FU-NPs in rat plasma were investigated by high-performance liquid chromatography (HPLC). The in vivo tumor inhibition effect, increase in lifespan and hepatotoxicity of placebo-NPs, 5-FU and 5-FU-NPs were determined using H22 tumor-bearing ICR mice. These results collectively suggest that 5-FU-NPs prepared using SEDS have potential anti-tumor applications as a controlled drug release dosage form without harmful drug toxicity. Crown Copyright (c) 2012 Published by Elsevier B.V. All rights reserved.
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