title: Entrapment of epirubicin in poly(butyl cyanoacrylate) colloidal nanospheres by nanoprecipitation: formulation development and in vitro studies on cancer cell lines.
abstract: This report describes the preparation of poly(butyl cyanoacrylate) nanospheres loaded with epirubicin by nanoprecipitation, their characterization and in vitro evaluation of the drug uptake and cytotoxicity on cancer cell lines. The epirubicin-loaded nanospheres were prepared by nanoprecipitation using presynthesized polymer and dextran 40 as a colloidal stabilizer at different pH and initial drug concentrations. The nanospheres were characterized for particle morphology, size distribution, zeta-potential and drug loading. Epirubicin-loaded particles with diameters around 350 nm were obtained. Drug loading depended on the pH and epirubicin concentration. Epirubicin was more cytotoxic when loaded in nanospheres. Drug release was studied by dialysis method. Cytotoxicity and drug uptake experiments were performed on HeLa and A549 cell lines. It was found that addition of polysorbate 80 could increase cytotoxicity. The cytotoxicity was found to correlate with the drug uptake by cells. The findings reported here demonstrate that epirubicin-loaded nanospheres of poly(butyl cyanoacrylate) can be successfully prepared by the nanoprecipitation approach as alternative to the well-known polymerization-based methods. It is found that the epirubicin-loaded nanospheres are more cytotoxic than the free drug to human carcinoma cell lines in vitro. The higher cytotoxicity of the obtained epirubicin formulations, compared with the free drug, is due to enhanced cellular internalization of epirubicin.
authors.affiliation: Sofia University St. Kliment Ohridski, Faculty of Chemistry, Sofia, Bulgaria. g.g.yordanov@gmail.com
authors.forename: Georgi
authors.initials: G
authors.lastname: Yordanov
authors.forename: Ralica
authors.initials: R
authors.lastname: Skrobanska
authors.forename: Alexander
authors.initials: A
authors.lastname: Evangelatov
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003102:Colloids; D003956:Dialysis; D004659:Enbucrilate / Q000737:chemistry*; D015251:Epirubicin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008857:Microscopy, Interference; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size
chemical_list: D003102:Colloids; D015251:Epirubicin; D004659:Enbucrilate