Cytotoxicity of anticancer drugs incorporated in solid lipid nanoparticles on HT-29 colorectal cancer cell line

• Published in: European journal of pharmaceutics and biopharmaceutics 2004-11, Vol.58 (3), p.673-680
• Main Authors: Serpe, L., Catalano, M.G., Cavalli, R., Ugazio, E., Bosco, O., Canaparo, R., Muntoni, E., Frairia, R., Gasco, M.R., Eandi, M., Zara, G.P.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - toxicity; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - toxicity; Butyric Acid - administration & dosage; Butyric Acid - pharmacokinetics; Butyric Acid - toxicity; Cell Survival - drug effects; Cell Survival - physiology; Cholesterol Esters - administration & dosage; Cholesterol Esters - pharmacokinetics; Cholesterol Esters - toxicity; Cholesteryl butyrate; Colorectal Neoplasms - drug therapy; Dose-Response Relationship, Drug; Doxorubicin; HT29 Cells; Humans; Nanostructures - toxicity; Paclitaxel; Sodium butyrate; Solid lipid nanoparticles
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2004.03.026

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 (IC 50) values were interpolated from growth curves obtained by trypan blue exclusion assay. In vitro cytotoxicity of SLN carrying chol-but (IC 50 72 h 0.3±0.03 mM vs >0.6 mM) and doxorubicin (IC 50 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 (IC 50 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 paclitaxel did not. These preliminary in vitro results suggest that SLN could be proposed as alternative drug delivery system.