Entrapment of epirubicin in poly(butyl cyanoacrylate) colloidal nanospheres by nanoprecipitation: Formulation development and in vitro studies on cancer cell lines

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.

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► Epirubicin-loaded PBCA nanospheres can be prepared by nanoprecipitation.
► In vitro studies of cytotoxicity and drug uptake are performed on A549 and HeLa cancer cell lines.
► Drug loading depended on the pH and epirubicin concentration.
► The increased cytotoxicity of the formulation correlated with increased drug uptake.