Floxuridine is a very effective drug with high potency in the treatment of various tumors but its utility is limited by its low efficiency of cellular uptake. In order to improve the floxuridine efficiency of cellular uptake, lipophilic prodrug of floxuridine (3′,5′-distearoyl-5-fluoro-2′-deoxyuridine) was synthetized and loaded into behenic acid nanoparticles produced by fatty acid coacervation technique. Generally, spherical shaped SLN with mean diameters below 300 nm were obtained. Distearoyl-floxuridine was loaded in SLN with high entrapment efficiency (from 70.8 to 82.8%). In Vitro cytotoxicity studies on different human cancer cell lines (M14, HT-29 and MDA-MB231) were performed in order to test the ability of distearoyl-floxuridine-SLN to inhibit the cancer cell growth. In MTT test distearoyl floxuridine SLN showed a greater efficacy than floxuridine on all cancer cell lines revealing an efficiency about 100 times higher. Also clonogenic assay showed a higher cytotoxicity of distearoyl-floxuridine-SLN compared to floxuridine but the difference between the formulations was only about 10 times. In conclusion, SLN proved to be a promising vehicle to increase the floxuridine efficacy in cancer therapy.

Lipophilic prodrug of floxuridine loaded into solid lipid nanoparticles: In vitro cytotoxicity studies on different human cancer cell lines

Chirio, Daniela
First
;
Peira, Elena;Battaglia, Luigi;Ferrara, Benedetta;Barge, Alessandro;Sapino, Simona;Giordano, Susanna;Dianzani, Chiara;Gallarate, Marina
Last
2018-01-01

Abstract

Floxuridine is a very effective drug with high potency in the treatment of various tumors but its utility is limited by its low efficiency of cellular uptake. In order to improve the floxuridine efficiency of cellular uptake, lipophilic prodrug of floxuridine (3′,5′-distearoyl-5-fluoro-2′-deoxyuridine) was synthetized and loaded into behenic acid nanoparticles produced by fatty acid coacervation technique. Generally, spherical shaped SLN with mean diameters below 300 nm were obtained. Distearoyl-floxuridine was loaded in SLN with high entrapment efficiency (from 70.8 to 82.8%). In Vitro cytotoxicity studies on different human cancer cell lines (M14, HT-29 and MDA-MB231) were performed in order to test the ability of distearoyl-floxuridine-SLN to inhibit the cancer cell growth. In MTT test distearoyl floxuridine SLN showed a greater efficacy than floxuridine on all cancer cell lines revealing an efficiency about 100 times higher. Also clonogenic assay showed a higher cytotoxicity of distearoyl-floxuridine-SLN compared to floxuridine but the difference between the formulations was only about 10 times. In conclusion, SLN proved to be a promising vehicle to increase the floxuridine efficacy in cancer therapy.
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http://www.ingentaconnect.com/content/asp/jnn/2018/00000018/00000001/art00079
Cancer, Clonogenic, Floxuridine, In Vitro Cytotoxicity, MTT, Prodrug
Chirio, Daniela; Peira, Elena; Battaglia, Luigi; Ferrara, Benedetta; Barge, Alessandro; Sapino, Simona; Giordano, Susanna; Dianzani, Chiara; Gallarate, Marina
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1655802
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