Effect of particle size of nanospheres and microspheres on the cellular-association and cytotoxicity of paclitaxel in 4T1 cells
| Autor: | Dennis H. Robinson, Donald W. Miller, Sinjan De |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Boron Compounds
ATP Binding Cassette Transporter Subfamily B Paclitaxel Cell Survival Polymers Chemistry Pharmaceutical In vitro cytotoxicity Pharmacology toxicology Pharmaceutical Science Deoxyglucose Microsphere chemistry.chemical_compound Polylactic Acid-Polyglycolic Acid Copolymer Cell Line Tumor Animals Pharmacology (medical) Lactic Acid Particle Size Cytotoxicity Etoposide Pharmacology Polylactic acid-polyglycolic acid copolymer Nanotubes Chemistry Organic Chemistry Brain Endocytosis Microspheres Cell culture Biophysics Cyclosporine Molecular Medicine Cattle Particle size Endothelium Vascular Drug Screening Assays Antitumor Polyglycolic Acid Biotechnology |
| Zdroj: | Pharmaceutical research. 22(5) |
| ISSN: | 0724-8741 |
| Popis: | To compare the effect of size of delivery systems on the cell-association and in vitro cytotoxicity of paclitaxel.Four sizes of PLGA-paclitaxel particles were prepared to study the effect of particle size on the cell-association of paclitaxel in 4T1 monolayer in the presence, and absence, of BCRP inhibitor, endocytic inhibitor, and P-glycoprotein (P-gp) inhibitor. Paclitaxel cell-association studies were repeated in Caco-2, Cor-L23/R, and bovine brain microvessel endothelial cells (BBMECs), as well as the association of etoposide in 4T1 cells. Cytotoxicity of paclitaxel to 4T1 cells delivered in nanospheres was compared to microspheres.The concentration of paclitaxel and etoposide associated with 4T1 cells was 4.8 and 29 times greater, respectively, as the size increased from 310 to 2077 nm. Paclitaxel association consistently increased in Caco-2 and Cor-L23/R as the size of the delivery system increased. The endocytic inhibitor, 2-deoxyglucose, significantly decreased the cellular paclitaxel association when delivered by nanospheres but not microspheres. Consistent with the cell-association results, paclitaxel was thrice more cytotoxic to 4T1 cells when delivered in microspheres.Cell-association of paclitaxel increased in 4T1, Caco-2, and Cor-L23/R as particle size increased. Paclitaxel delivered from 1-mum microspheres was thrice more cytotoxic to 4T1 cells compared to the drug delivered from nanospheres or solution. |
| Databáze: | OpenAIRE |
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