Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 58, Issue 3, Pages 673-680Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2004.03.026
Keywords
solid lipid nanoparticles; sodium butyrate; cholesteryl butyrate; doxorubicin; paclitaxel
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Solid lipid nanoparticles (SLN) carrying cholesteryl butyrate (chol-but), doxorubicin and paclitaxel had previously been developed, and the antiproliferative effect of SLN formulations versus conventional drug formulations was here evaluated on HT-29 cells. The 50% inhibitory concentration (IC50) values were interpolated from growth curves obtained by trypan blue exclusion assay. In vitro cytotoxicity of SLN carrying chol-but (IC50 (72) h 0.3 +/- 0.03 mM vs > 0.6 mM) and doxorubicin IC50 (72) (h) 81.87 +/- 4.11 vs 126.57 +/- 0.72 nM) was higher than that of conventional drug formulations. Intracellular doxorubicin was double after 24 h exposure to loaded SLN versus the conventional drug formulation, at the highest concentration evaluated by flow cytometry. In vitro cytotoxicities of paclitaxel-loaded SLN and conventional drug formulation (IC50 (72 h) 37.36 +/- 6.41 vs 33.43 +/-1.17 nM) were similar. Moreover, the combination of low concentrations of chol-but SLN (0.1-0.2 mM) and doxorubicin (1.72 nM) or paclitaxel (1.17 nM) exerted a greater-than-additive antiproliferative effect at 24 h exposure, while the combination of Na-but and doxorubicin or pactitaxel did not. These preliminary in vitro results suggest that SLN could be proposed as alternative drug delivery system. (C) 2004 Elsevier B.V. All rights reserved.
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